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https://f1000research.com/articles/13-1495/v1
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06 Dec 24
|
{
"type": "Systematic Review",
"title": "Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review",
"authors": [
"Albandri Mohammed Alowid",
"Mamata Hebbal",
"Fatimah Salim Almufarji",
"Ghadeer Ghalab Almutairi",
"Shahad Saad Alkait",
"Praveen Jodalli",
"Albandri Mohammed Alowid",
"Mamata Hebbal",
"Fatimah Salim Almufarji",
"Ghadeer Ghalab Almutairi",
"Shahad Saad Alkait"
],
"abstract": "Background Silver diamine fluoride (SDF) is recognized for its potent antibacterial properties and is commonly used in dentistry to treat carious lesions. This review aims to evaluate the antimicrobial effect of SDF on dentine caries in permanent teeth. The objective is to provide a comprehensive analysis of the existing literature to assess the efficacy of SDF in combating cariogenic flora within dentin lesions.\n\nMaterials and Methods A systematic electronic search was conducted using Google Scholar, Cochrane Library, and PubMed databases to identify relevant studies published between January 2010 and September 2022. The search strategy focused on retrieving in vitro and in vivo studies assessing the antimicrobial effect of SDF on dentinal caries. The inclusion criteria encompassed studies that compared SDF with other antimicrobial agents, such as sodium fluoride varnish, potassium iodide, silver nitrate, chlorhexidine, plasma jet, and deionized water. The Cochrane Collaboration assessment tool was employed to evaluate the risk of bias in the included studies.\n\nResults Nine studies met the inclusion criteria, consisting of seven in vitro and in situ studies investigating the antimicrobial effect of SDF on dentinal caries, and two in vitro and in vivo studies examining its antibacterial effect on root caries. These studies collectively demonstrated the promising antimicrobial potential of SDF against cariogenic flora present in dentin lesions. However, variations in study design, methodology, and outcome measures were observed across the included studies.\n\nConclusion The review underscores the significant antimicrobial efficacy of SDF in combating cariogenic bacteria within dentin lesions of permanent teeth. Despite the promising findings, there remains a lack of comprehensive understanding regarding the precise characteristics and mechanisms underlying the antimicrobial action of SDF, particularly concerning nano-silver. Future research, including long-term clinical trials, is warranted to elucidate optimal dosage regimens and therapeutic approaches for the routine application of SDF in managing dental caries.",
"keywords": [
": Prevention",
"Silver diamine fluoride",
"Remineralization",
"Antimicrobial effect",
"Dentine caries"
],
"content": "Introduction\n\nDental caries is the predominant chronic disease affecting both children and adults, leading to significant health burdens globally. Researchers continually strive to find effective management strategies, with minimally invasive techniques emerging as a conservative approach to treating carious teeth. These techniques aim to preserve some of the carious dentin structure before applying a restoration. As part of this approach, antimicrobial agents such as silver diamine fluoride (SDF), sodium hypochlorite, and chlorhexidine are implemented to disinfect the cavity and halt the progression of caries. Silver diamine fluoride, a topical solution comprising fluoride and silver ions, has a long-standing history in medicine and dentistry due to its notable antibacterial properties. Before the advent of antibiotics and amid rising antimicrobial resistance, silver compounds were extensively used for their therapeutic attributes. Today, silver is once again esteemed as an antimicrobial agent for its broad-spectrum activity, low toxicity, and lack of bacterial cross-resistance, particularly within the field of dentistry. Since the 1960s, the combination of silver with fluoride has been promoted as an anti-caries agent, demonstrating significant effectiveness.1\n\nSDF is conventionally used at a 38% concentration, although a 12% formulation is also available. However, clinical studies have indicated that the lower concentration is not as efficacious as the 38% solution in arresting dental caries in children.2,3 It is particularly indicated for patients with cavitated lesions who face medical management challenges, have difficult carious lesions, carry multiple cavitated carious lesions, are at high risk of caries, or have limited access to dental care.2 Its affordability, straightforward application, non-invasive nature, and minimal application time make SDF an optimal solution for quick, cost-effective, and efficient caries prevention and arrest.2,3\n\nClinical studies have demonstrated that SDF can prevent and arrest coronal caries in preschool children’s primary teeth and in the permanent teeth of older children.4 SDF has been shown to be a more effective option for caries control than intermediate restorative treatments, such as glass ionomer sealants, in deciduous teeth.,5 Oliveira et al. conducted a systematic review and meta-analysis evaluating the effectiveness of SDF in caries prevention for primary dentition, finding that 38% SDF application reduced the dental caries by 77% in treated children compared to untreated ones.6 Moreover, Chibinski et al. reported that SDF is effective compared to fluoride treatments by 89%.7 However, these studies predominantly focus on caries arrest and prevention in primary dentition and do not comprehensively assess the antimicrobial effect of SDF on permanent teeth, particularly regarding dentinal caries arrest. The objective of this systematic review is to determine the antimicrobial effect of silver diamine fluoride on dentine caries in permanent teeth.\n\nGiven the rising incidence of dental caries and the need for effective, non-invasive treatments, this systematic review aims to bridge the knowledge gap regarding the antimicrobial effects of SDF on permanent teeth. While substantial evidence supports its efficacy in primary teeth, less is known about its performance in adult dentition, especially in arresting dentinal caries. Understanding this aspect could enhance clinical protocols and offer a broader application of SDF, providing a potent tool in dental public health. This review will critically assess existing studies, aiming to provide a comprehensive evaluation of SDF’s antimicrobial capabilities in permanent teeth, thereby guiding future research and clinical practice.\n\n\nMethods\n\nAn electronic search was conducted using the Google Scholar, Cochrane Library, and PubMed databases. All published in vitro and in vivo studies from January 2010 to September 2022 were included. The review question was formulated using the PICO framework: “Does silver diamine fluoride (I) have an antimicrobial effect (O) on dentinal caries in permanent teeth (P)?” The search keywords used were: (permanent teeth) AND (caries arrest) AND ((SDF) OR (silver diamine fluoride)) AND ((antimicrobial effect) OR (microbial reduction)) AND ((dentin caries) OR (dentinal caries)).\n\nThe inclusion criteria were:\n\n• In vitro and in vivo studies\n\n• Published in English\n\n• Focus on dentinal caries in permanent teeth\n\n• Examination of antimicrobial effects\n\n• Caries arrest using silver diamine fluoride\n\nThe exclusion criteria were:\n\n• Resources other than articles (e.g., books)\n\n• Non-English language publications\n\n• Studies on enamel/cementum caries or primary/bovine teeth\n\n• Studies not mentioning the antimicrobial effect\n\n• Studies not related to caries arrest\n\n• Studies combining silver diamine fluoride with other materials\n\nResearch articles were collected using Mendeley Desktop 1.19.8 for Windows. The electronic data search and analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy and results are summarized in a PRISMA flow diagram (Figure 1).\n\nInitially, 566 records were identified and collected from the three databases. After removing 16 duplicates, 40 non-English language articles, 55 theses, 31 books, and 4 conference proceedings, the remaining records were screened. Titles and abstracts were reviewed, and articles meeting the predetermined inclusion criteria were selected. Nine studies were retrieved, and their full texts were screened to ensure they met the eligibility criteria. References from the selected articles were also reviewed to identify additional studies for inclusion.\n\nData extraction and analysis were conducted by two authors independently in multiple steps. Any discrepancies were resolved by a third reviewer, who independently reviewed the articles, and a decision was made based on the majority consensus. The extracted data included study design, sample size, interventions, outcomes, and conclusions.\n\nThe risk of bias was assessed using the Cochrane Collaboration assessment tool to evaluate the methodological quality of the included studies. Each researcher conducted the risk assessment independently, and any disagreements were discussed and resolved to reach a mutual decision. The risk of bias for each study was documented as low, unclear, or high and summarized in Table 1.\n\nA narrative synthesis of the results was performed due to the heterogeneity of the included studies. The antimicrobial effect of SDF on dentinal caries in permanent teeth was evaluated based on the reported outcomes. Meta-analysis was not conducted due to the variability in study designs, sample sizes, and outcome measures. Table 2\n\nAs this study is a systematic review, it does not involve direct human or animal subjects, and thus, ethical approval was not required. However, all included studies were checked for their ethical approvals and declarations of informed consent.\n\n\nResults\n\nThe primary objective of this systematic review was to determine the antimicrobial effect of silver diamine fluoride (SDF) on dentinal carious lesions in permanent teeth. The results are presented in two stages: in vivo and in vitro studies, with a summary of the information, reviewers’ assessments, and critical appraisals. Additionally, we investigated whether SDF behaves differently on occlusal dentinal caries compared to root dentinal caries.\n\nSeven clinical studies were retrieved to investigate the effect of SDF treatment on dentinal caries in permanent teeth.\n\nMei et al., 2013 evaluated the effect of 38% SDF on cariogenic biofilms and dentin carious lesions using five common cariogenic bacteria. Twelve dentin blocks were treated with SDF, and 12 with water, then incubated for 21 days. The results showed reduced bacterial growth and improved tooth mineral content in the SDF group compared to the control group (p < 0.01).8\n\nIn 2011, Chu et al. conducted a study to examine the effects of SDF on dentine caries induced by Streptococcus mutans and Actinomyces naeslundii using artificially demineralized human dentine blocks. The results indicated reduced biofilm counts in the SDF group compared to the control (p < 0.01). Surfaces of carious lesions due to S. mutans were harder (p < 0.05) in the SDF group, while calcium and phosphate content also showed significant reductions after SDF treatment (p < 0.05). These findings suggest that SDF has antimicrobial activity against cariogenic biofilms of both bacteria and slows down dentine demineralization.9\n\nYu et al., 2018 conducted a study on the effects of SDF solution followed by NaF varnish in treating dentine caries. They used 104 dentine blocks from human third molars, with different groups receiving various treatments and assessments for demineralization and biofilm. The results indicated that the combination of SDF and NaF had a more significant effect on lesion depth compared to individual treatments, showing higher antibacterial effects as well.10\n\nAbdullah et al., 2020 conducted a study to assess the antimicrobial effectiveness of various SDF materials. They used in-situ biofilms from five participants and allowed them to grow for 6 hours. The study compared the anti-biofilm efficacy of different concentrations of SDF, as well as combinations with potassium iodide. The results indicated that all samples treated with 38% SDF showed a significant decrease in viable bacteria compared to the negative control (sterile distilled water). There was also no additional antibacterial effect observed when KI was supplemented with SDF.11\n\nMei et al., 2013 conducted an in vitro study to investigate the antimicrobial effect of SDF on Streptococcus mutans and Lactobacillus acidophilus co-cultured dual-species biofilm and dentine caries lesions. Dentine blocks from human third molars were inoculated with bacteria, divided into test and control groups, treated with SDF or water, and incubated for 7 days at 37°C. The results showed a significant reduction in CFU counts of both bacteria in the SDF group compared to the control group. SEM images indicated that more bacteria were dead in the SDF group than in the control group. CLSM images also demonstrated a higher dead-to-live ratio after SDF application compared to water. FTIR analysis revealed differences between the log Amide I:HPO42- ratio of the two groups, as did gold-labeling density.12\n\nMei et al. (2013) further investigated the antagonistic impact of 38% SDF on demineralized dentin. The experiment included 18 blocks of demineralized human dentine that were divided into four groups: one that received a 38% SDF solution, another that received a 10% sodium fluoride solution, a fourth that received a 42% silver nitrate solution, and the control group received deionized water. In the SDF group, smooth, unexposed collagen fibers of dentin were observed. Some collagen fibers were exposed and relatively rough in the sodium fluoride group. In contrast, demineralization resulted in evident exposure of collagen fibers in the silver nitrate and water groups. The mean lesion depth of the silver nitrate and water groups were 259 ± 42 mm and 265 ± 40 mm, respectively, which were significantly higher than those of the SDF and sodium fluoride groups, which were 182 ± 32 mm and 204 ± 26 mm, respectively. The amount of hydroxyproline (HYP), a non-proteinogenic amino acid, in the remineralization solution was used to measure collagen degradation. In contrast to the water (469 ± 63 mg/mL) and sodium fluoride (189 ± 85 mg/mL) groups, the amounts in the SDF (346 ± 57 mg/mL) and silver nitrate (349 ± 18 mg/mL) groups were noticeably higher.13\n\nIrene Zhao et al. (2017) performed an in vitro investigation to see whether a silver nitrate solution and a sodium fluoride varnish might halt the progression of caries. A total of fifty-four dentine slices taken from human third molars were demineralized and processed. After that, the slices were split into three groups: SF, which consisted of 25% silver nitrate and 5% sodium fluoride varnish; SDF, which was a 38% silver diamine fluoride solution and was used as a positive control; and deionized water, which as a negative control. The water group showed exposed dentine collagen fibres, but the SF and SDF groups showed intact and smooth fibres, according to scanning electron microscopy. Both the SDF and SF groups showed less depth of lesion in typical micro-CT images when compared to the water group. There was a statistically significant difference between the water group’s lesion depth (258 ± 53 μm) and the SDF and SF groups, with the former having a mean lesion depth of 135 ± 24 μm and the latter of 128 ± 19 μm, respectively. Moreover, in comparison to the water group (339 ± 16 μg/ml), the SF and SDF groups had a noticeably reduced concentration of hydroxyproline (HYP) in the remineralization solution (312 ± 11 μg/ml and 317 ± 16 μg/ml, respectively).14\n\nHertel et al.’s 2018 in vitro study aimed to assess the bactericidal efficacy of silver diamine fluoride (SDF), cold atmospheric plasmas (CAPs), and chlorhexidine (CHX) in root caries lesions. They created artificial root carious lesions in 50 human dentin samples, dividing them into four groups: two test groups (plasma jet and dielectric barrier discharge source) and two control groups (CHX and SDF varnishes), with a negative control group treated using a blank micro brush to remove nonadherent biofilm. All applied agents resulted in significantly lower colony-forming unit (CFU) counts compared to the control (p ≤ 0.01). When comparing the four treatment agents, only SDF showed a significant decrease in CFU counts (p = 0.004) compared to the dielectric barrier discharge source.15\n\nOn the other hand, Karched et al.’s 2019 in vivo study aimed to determine the antimicrobial efficacy of SDF and SDF with potassium iodide. They conducted their study on five patients, each with at least five lesions. Four different agents (SDF, SDF + potassium iodide, chlorhexidine, and sterile saline) were applied to four carious lesions separately in each patient. The mean inhibition zone of S. mutans CCUG 11877 was 25.7 mm, displaying the highest susceptibility to SDF. In the SDF + KI group, the inhibitory zone decreased to 15.15 mm. The inhibition zone of chlorhexidine was 23 mm, while no inhibition was observed in the negative control saline group. The total viable counts of anaerobes were reduced by over 90% after treatment with SDF or SDF + KI, with complete reduction observed in total viable counts of mitis salivarius-bacitracin (MSB) agar. Treatment with SDF decreased the median CFU counts from 9 × 105 to 1.6 × 102 per mg dentin, while in the SDF + KI group, the counts reduced from 2.9 × 105 to 9.2 × 10 per mg dentin. Treatment with chlorhexidine also significantly reduced the median CFU counts. Lesions treated with sterile saline showed no effect on viable counts. Following treatment with SDF, complete inhibition of bacterial growth on Brucella agar was observed in two out of five subjects, with all subjects treated with SDF showing no bacterial growth on MSB agar plates. Complete inhibition of bacterial growth was evident in four out of five subjects following SDF + KI treatment.16 Neither study mentioned a difference in the mechanism of action or behavior of SDF in the crown or root of the tooth. All studies revealed bacterial inhibition after using SDF in both root and occlusal caries.\n\n\nDiscussion\n\nSDF has been called silver diamine fluoride, ammoniated silver fluoride, and ammoniacal silver fluoride since 1969.1 The accurate terminology is silver diamine fluoride, which has two ammine groups (NH3), however it is sometimes mispronounced. This led to the term “diamine” being used extensively in both academic and marketing contexts. The common ingredients in SDF are ammonia, silver, and fluoride, though the exact amount of fluoride might fluctuate across brands.2,16 SDF is effective because it combines fluorides and silver nitrates, which is the composition of the compound. By inhibiting collagenase, reducing dentin collagen matrix, and promoting remineralization, SDF inhibits or prevents dental caries.3 It also has an antibacterial effect against dental caries. Particulate silver ions have several proposed means of microbial death, but the specific mechanisms by which they kill bacteria and fungi remain unclear. Some of these mechanisms involve the capacitive binding of silver ions to anionic components of microbial cell membranes. This can cause cell death, cell motility to be rendered ineffective (in motile bacteria), and leakage of cell contents.17 Additionally, some silver ions may act as toxic poisons, inhibiting metabolic enzymes and blocking electron transport chains.18\n\nFurthermore, Chu et al. suggested in their laboratory study that SDF directly inhibits the growth of Streptococcus mutans or Actinomyces naeslundii mono-species biofilms and promotes acid attack resistance in dentin through the reaction of calcium fluoride with hydroxyapatite.9 The high pH of SDF also negatively affects bacterial viability by disintegrating bacterial cell envelopes through the phosphorous and sulfur components of the bacterial cell wall, combined with the reactivity of silver ions, resulting in an antibacterial effect.19 It has been reported that SDF and the combination of SDF with potassium iodide have eliminated bacteria in mitis salivarius-bacitracin (MSB).16 However, an in-situ study found no additional value in using KI with SDF in terms of antimicrobial effect.11 Similarly, an in vivo study showed a better antibacterial effect of SDF and the combination of SDF with potassium iodide compared to chlorhexidine, although this difference was not statistically significant.16\n\nSeveral studies have demonstrated the superior antimicrobial effect of SDF compared to chlorhexidine as an antimicrobial agent.20,21 Abdullah et al. found no significant difference in the residual viable biofilm bacteria between the SDF and CHX groups in situ samples.11 Numerous in vitro and in vivo studies have investigated the use of silver compounds in managing human dental caries in permanent teeth.22,23 However, to our knowledge, there has not been a systematic review that comprehensively examines the antibacterial effect of SDF in arresting dentin caries on permanent teeth and its mechanism of action in both root and crown caries.\n\n\nConclusion\n\nThe review of available studies underscores the promising antimicrobial potential of silver-based formulations, such as SDF, against the cariogenic flora prevalent in dentin lesions. However, there remains a significant gap in our understanding regarding the precise size, concentration, antibacterial mechanisms, and toxicological characteristics of nano-silver. To establish a robust foundation for the regular utilization of silver-based compounds as anti-cariogenic agents, it is imperative to generate conclusive evidence through meticulous standardization of experimental protocols, outcome evaluation criteria, and analyses. Clearly, long-term clinical trials are indispensable to gather substantial evidence for making definitive recommendations. Such trials should aim to address the existing knowledge gaps concerning the optimal dosage and therapeutic regimens for the routine application of SDF against polymicrobial consortia present in caries-affected dentin. Through rigorous scientific inquiry and comprehensive clinical investigations, we can advance our understanding and maximize the efficacy of SDF in combating dental caries effectively.\n\n\nReporting guidelines\n\nRepository: PRISMA checklist for ‘Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review’. https://doi.org/10.6084/m9.figshare.27814644.24\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nZhao IS, Mei ML, Burrow MF, et al.: Effect of silver diamine fluoride and potassium iodide treatment on secondary caries prevention and tooth discoloration in cervical glass ionomer cement restoration. Int. J. Mol. Sci. 2017 Feb 6; 18(2): 340. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMishra A, Sahoo P, Ray P, et al.: Silver Diamine Fluoride: Journey from Silver bullet to Magic Bullet. Int. J. Sci. Res. 2019.\n\nRosenblatt AT, Stamford TC, Niederman R: Silver diamine fluoride: a caries “silver-fluoride bullet”. J. Dent. Res. 2009 Feb; 88(2): 116–125. PubMed Abstract | Publisher Full Text\n\nLlodra JC, Rodriguez A, Ferrer B, et al.: Efficacy of silver diamine fluoride for caries reduction in primary teeth and first permanent molars of schoolchildren: 36-month clinical trial. J. Dent. Res. 2005 Aug; 84(8): 721–724. PubMed Abstract | Publisher Full Text\n\nChou R, Cantor A, Zakher B, et al.: Preventing dental caries in children< 5 years: systematic review updating USPSTF recommendation. Pediatrics. 2013 Aug 1; 132(2): 332–350. Publisher Full Text\n\nOliveira BH, Rajendra A, Veitz-Keenan A, et al.: The effect of silver diamine fluoride in preventing caries in the primary dentition: a systematic review and meta-analysis. Caries Res. 2019 Jun 6; 53(1): 24–32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChibinski AC, Wambier LM, Feltrin J, et al.: Silver diamine fluoride has efficacy in controlling caries progression in primary teeth: a systematic review and meta-analysis. Caries Res. 2017 Oct 4; 51(5): 527–541. PubMed Abstract | Publisher Full Text\n\nMei ML, Li QL, Chu CH, et al.: Antibacterial effects of silver diamine fluoride on multi-species cariogenic biofilm on caries. Ann. Clin. Microbiol. Antimicrob. 2013 Jan; 12: 1–7. Publisher Full Text\n\nChu CH, Mei LE, Seneviratne CJ, et al.: Effects of silver diamine fluoride on dentine carious lesions induced by Streptococcus mutans and Actinomyces naeslundii biofilms. Int. J. Paediatr. Dent. 2012 Jan; 22(1): 2–10. Publisher Full Text\n\nOllie YY, Zhao IS, Mei ML, et al.: Caries-arresting effects of silver diamine fluoride and sodium fluoride on dentine caries lesions. J. Dent. 2018 Nov 1; 78: 65–71. Publisher Full Text\n\nAbdullah N, Al Marzooq F, Mohamad S, et al.: The antibacterial efficacy of silver diamine fluoride (SDF) is not modulated by potassium iodide (KI) supplements: A study on in-situ plaque biofilms using viability real-time PCR with propidium monoazide. PLoS One. 2020 Nov 3; 15(11): e0241519. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMei ML, Chu CH, Low KH, et al.: Caries arresting effect of silver diamine fluoride on dentine carious lesion with S. mutans and L. acidophilus dual-species cariogenic biofilm. Med. Oral Patol. Oral Cir. Bucal. 2013 Nov; 18(6): e824–e831. PubMed Abstract | Publisher Full Text\n\nMei L, Ito L, Cao Y, et al.: Effect of silver-diamine-fluoride on dentine demineralisation and collagen degradation. J. Dent. Res. 2013; 41: 809–817. PubMed Abstract | Publisher Full Text\n\nZhao IS, Mei ML, Li QL, et al.: Arresting simulated dentine caries with adjunctive application of silver nitrate solution and sodium fluoride varnish: an in vitro study. Int. Dent. J. 2017 Aug 1; 67(4): 206–214. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHertel M, Schwill-Engelhardt J, Gerling T, et al.: Antibacterial efficacy of plasma jet, dielectric barrier discharge, chlorhexidine, and silver diamine fluoride varnishes in caries lesions. Plasma Med. 2018; 8(1): 73–82. Publisher Full Text\n\nKarched M, Ali D, Ngo H: In vivo antimicrobial activity of silver diammine fluoride on carious lesions in dentin. J. Oral Sci. 2019; 61(1): 19–24. PubMed Abstract | Publisher Full Text\n\nNuvvula S, Mallineni SK: Silver diamine fluoride in pediatric dentistry. Journal of South Asian Association of Pediatric Dentistry. 2019 Jul; 2(2): 73–80. Publisher Full Text\n\nFakhruddin KS, Egusa H, Ngo HC, et al.: Clinical efficacy and the antimicrobial potential of silver formulations in arresting dental caries: a systematic review. BMC Oral Health. 2020 Dec; 20: 1–3. Publisher Full Text\n\nMorones JR, Elechiguerra JL, Camacho A, et al.: The bactericidal effect of silver nanoparticles. Nanotechnology. 2005 Aug 26; 16(10): 2346–2353. Publisher Full Text\n\nHamama HH, Yiu CK, Burrow MF: Effect of silver diamine fluoride and potassium iodide on residual bacteria in dentinal tubules. Aust. Dent. J. 2015 Mar; 60(1): 80–87. PubMed Abstract | Publisher Full Text\n\nBesinis A, De Peralta T, Handy RD: Inhibition of biofilm formation and antibacterial properties of a silver nano-coating on human dentine. Nanotoxicology. 2014 Nov 1; 8(7): 745–754. PubMed Abstract | Publisher Full Text\n\nFakhruddin KS, Egusa H, Ngo HC, et al.: Clinical efficacy and the antimicrobial potential of silver formulations in arresting dental caries: a systematic review. BMC Oral Health. 2020 Dec; 20: 1–3. Publisher Full Text\n\nShah S, Bhaskar V, Venkatraghavan K, et al.: Silver diamine fluoride: a review and current applications. J. Adv. Oral Res. 2014 Jan; 5(1): 25–35. Publisher Full Text\n\nPraveen J: Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review. [Dataset]. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "364143",
"date": "07 Feb 2025",
"name": "Nishant Mehta",
"expertise": [
"Reviewer Expertise Public Health Dentistry & Preventive Dentistry",
"Tobacco & Oral Microbiome Research",
"Cancer & Oral Mucositis Research"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview summary: The topic's area and scope are well justified, given the high burden of dental caries among adults and the limited cost-effective strategies available. The introduction is built upon existing literature and highlights the need for the study. The methods section adequately describes the search strategy, inclusion/exclusion criteria, and risk of bias assessment. Provides valuable insights about future implications and effectively summarizes key findings of the study. Recommendations: Abstract:\nPlease modify the conclusion to reflect upon the study objectives.\nMethods:\nPlease provide the search strategy as a supplementary file. Please remove duplicates from the Exclusion criteria; a) Studies not mentioning the antimicrobial effect and b) Studies not related to caries arrest Please mention if any restrictions on study design were made in the inclusion criteria to limit heterogeneity in included studies Kindly consider registering the review with PROSPERO if the same has not been done. Consider using JBI or QUIN tool for quality assessment of invitro studies.\nResults:\nKindly concise summary of included studies.\n\nPlease explicitly mention variability in the included studies leading to not carrying out pooled analysis.\nDiscussion:\n1st paragraph of discussion section gives an elaborated description of SDF mechanism which is beyond scope of this study. Please compare the effectiveness of SDF to other antimicrobial agents. Please elaborate upon study limitations e.g., short follow-up duration in studies, in vitro vs. in vivo differences etc.\nConclusion:\nPlease remove or refine speculative claims about nano-silver unless directly supported by the reviewed studies\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
},
{
"id": "364146",
"date": "07 Feb 2025",
"name": "Kiran Iyer",
"expertise": [
"Reviewer Expertise Oral Epidemiology",
"Bio-Statistics",
"Oral Health Utilization",
"AI in Oral Health"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAim: This review aimed to evaluate SDF’s antimicrobial capabilities in permanent teeth comprehensively, guiding future research and clinical practice. Search: In total 9 articles satisfied the final inclusion and exclusion criteria and were included for final review. The PICO-based search strategy has been found to include appropriate keywords. RoB: The risk of bias was assessed using the Cochrane Collaboration assessment tool to evaluate the methodological quality of the included studies- appropriate for interventional studies. Conclusion: this is very appropriate and in line with findings from studies, there is a need for many other variables to be considered before concluding on the role of nano silvers. Though promising there remains a significant gap in our understanding regarding the precise size, concentration, antibacterial mechanisms, and toxicological characteristics of nano-silver.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1495
|
https://f1000research.com/articles/13-1494/v1
|
06 Dec 24
|
{
"type": "Correspondence",
"title": "Comments about the comparative bulk RNA sequencing between palmoplantar pustulosis and dyshidrotic palmoplantar eczema",
"authors": [
"Kazuki Yatsuzuka",
"Jun Muto",
"Masamoto Murakami",
"Jun Muto",
"Masamoto Murakami"
],
"abstract": "This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell–related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE. We elaborate on histopathological differences, especially intraepidermal vesicle formation in PPP linked to IL–1–mediated pathways and the absence of hyaluronan expression, contrasting with Th2 cytokines-driven spongiosis in DPE. By addressing IL-4, hyaluronan synthases, and keratinocyte adhesion molecules, this correspondence aims to deepen understanding of PPP and DPE pathophysiology.",
"keywords": [
"palmoplantar pustulosis",
"dyshidrotic eczema",
"psoriasis",
"RNA sequencing",
"intraepidermal vesicle"
],
"content": "\n\nTo the Editor:\n\nWe read with great interest the recent report by Straalen et al.1 describing molecular overlap among inflammatory palmoplantar diseases, including palmoplantar pustulosis (PPP), palmoplantar psoriasis (palmPP), and dyshidrotic palmoplantar eczema (DPE). Their findings highlight shared upregulation of proinflammatory cytokines, chemokines, and T-cell–associated genes. Research in this field often lacks rigorous inclusion criteria, such as consistent diagnostic and sampling standards, making studies such as theirs—which has high reproducibility—extremely valuable for advancing global clinical trials. We sincerely commend their work. In addition to identifying shared molecular characteristics, the study elucidated unique features of each disease, such as enriched neutrophil processes in PPP (and, to a lesser extent, in palmPP) and lipid antigen processing in DPE.1 These findings further clarify the histological and pathophysiological differences between PPP and DPE, which are of particular interest to us.\n\nPPP is a persistent pustular skin condition that primarily affects the palms and soles. It is marked by the presence of erythema, pustules, and irregular peeling of the skin with or without psoriasis vulgaris.2 In Japan, PPP rarely co-occurs with psoriasis, whereas in Western countries, it is frequently associated with psoriasis. Our group has proposed subdividing PPP into type A (rarely associated with psoriasis) and type B (frequently associated with psoriasis).2 Type A PPP is distinguished by the clinical feature of intraepidermal vesicles preceding pustule formation.2 We recently demonstrated that interleukin (IL)-1 present in eccrine sweat could infiltrate the epidermis via the acrosyringium, impairing E-cadherin expression on keratinocytes and contributing to the development of intraepidermal vesicles in type A PPP.3 Conversely, the mechanisms underlying intraepidermal vesicle formation in DPE remain poorly understood. Spongiosis, a hallmark of eczema, is associated with hyaluronan production and reduced E-cadherin expression, driven by IL-4, IL-13, and interferon-γ (IFN-γ)-stimulated keratinocytes.4 Notably, we previously observed that keratinocytes around PPP-associated vesicles lack hyaluronan expression, unlike those in DPE.5 These findings strongly suggest that the mechanisms of intraepidermal vesicle formation differ between PPP and DPE.\n\nStraalen et al. confirmed and redefined clinical diagnoses of PPP and DPE using biopsy samples, diagnosing PPP based on “intraepidermal vesicles” without spongiosis and with potential microabscesses at the edges.1,6 These criteria align with type A PPP, increasing our interest in their study. The authors reported higher expression of IL-13 and IFN-γ in DPE than in PPP,1 which aligns with our understanding and represents an intriguing confirmation of these findings.\n\nTo elucidate further the pathophysiology of PPP and DPE, we invite the authors to share their opinions and any detailed findings regarding IL-4 expression, hyaluronan synthases 1 to 3, and intercellular adhesion factors of epidermal keratinocytes, such as cadherins and desmogleins.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Acknowledgements\n\nNone.\n\n\nData availability\n\nNo data are associated with this article.\n\n\nReferences\n\nvan Straalen KR , Kirma J, Yee CM, et al.: Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases. J. Allergy Clin. Immunol. 2024; 154(5): 1204–1215.e9. PubMed Abstract | Publisher Full Text\n\nMurakami M, Terui T: Palmoplantar pustulosis: Current understanding of disease definition and pathomechanism. J. Dermatol. Sci. 2020; 98(1): 13–19. PubMed Abstract | Publisher Full Text\n\nYatsuzuka K, Kawakami R, Niko Y, et al.: A fluorescence imaging technique suggests that sweat leakage in the epidermis contributes to the pathomechanism of palmoplantar pustulosis. Sci. Rep. 2024; 14(1): 378. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOhtani T, Memezawa A, Okuyama R, et al.: Increased hyaluronan production and decreased E-cadherin expression by cytokine-stimulated keratinocytes lead to spongiosis formation. J. Invest. Dermatol. 2009; 129(6): 1412–1420. PubMed Abstract | Publisher Full Text\n\nMurakami M, Muto J, Masuda-Kuroki K, et al.: Pompholyx vesicles contain small clusters of cells with high levels of hyaluronate resembling the pustulovesicles of palmoplantar pustulosis. Br. J. Dermatol. 2019; 181(6): 1325–1327. PubMed Abstract | Publisher Full Text\n\nMasuda-Kuroki K, Murakami M, Kishibe M, et al.: Diagnostic histopathological features distinguishing palmoplantar pustulosis from pompholyx. J. Dermatol. 2019; 46(5): 399–408. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "352002",
"date": "07 Jan 2025",
"name": "Yulong Sun",
"expertise": [
"Reviewer Expertise psoriasis"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe advent of high-throughput omics technologies, particularly bulk transcriptome sequencing, has revolutionized our understanding of complex diseases over the past two decades. This innovative approach has been crucial for elucidating disorders with overlapping clinical presentations, such as palmoplantar pustulosis (PPP), non-pustular palmoplantar psoriasis (palmPP), and wet palmoplantar eczema (DPE). In this context, the work of Straalen et al. offers valuable insights into the transcriptomic profiles of these closely related conditions. Their study includes a comprehensive analysis of disease samples, comprising lesion samples from PPP (n = 533), palmPP (n = 555), and DPE (n = 528), alongside skin samples from 10 healthy individuals and 5 healthy non-acral sites. This systematic mapping enhances our understanding of these three diseases and highlights the distinctive features of their immune microenvironments 1.\nKazuki Yatsuzuka et al. have provided a comprehensive summary of the work by Straalen et al., effectively analyzing the clinical characteristics and challenges associated with diagnosing and treating three specified skin diseases 2. They articulate the clinical significance of this research, emphasizing its relevance for improving diagnostic and therapeutic strategies in this field. The authors recommend a more nuanced molecular classification of Palmoplantar Psoriasis (PPP), particularly considering the frequent co-occurrence of psoriasis, which may enhance awareness and understanding of this condition. Furthermore, the authors elucidate the differing mechanisms underlying intraepidermal vesicle formation in each disorder by examining the pathophysiological and histological distinctions between PPP and Dyshidrotic Eczema (DPE). This insight offers a valuable foundation for accurately diagnosing and treating these often-confused conditions. Overall, this work has significant implications for advancing our understanding of dermatological research and clinical practice.\n\nIs the rationale for commenting on the previous publication clearly described? Yes\n\nAre any opinions stated well-argued, clear and cogent? Yes\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Yes\n\nIs the conclusion balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "13135",
"date": "14 Jan 2025",
"name": "Kazuki Yatsuzuka",
"role": "Author Response",
"response": "Thank you for taking your valuable time to review our paper. Sincerely, Kazuki Yatsuzuka"
}
]
},
{
"id": "352003",
"date": "13 Jan 2025",
"name": "Sueli Carneiro",
"expertise": [
"Reviewer Expertise Dermatology",
"Rheumatology and Immunodermatology and Immunorheumatology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors agree with the findings of Straalen et al. and confirm that the redefinition of the clinical diagnoses of PPP and DPE were of great clinical and histopathological value. The authors further state that such findings, criteria and definitions align with their type A PPP criteria, including in relation to greater expression of IL-13 and IFN-γ in DPE than in PPP. They close the communication by inviting authors to share their opinions and any other detailed findings on the expression of interleukins and cell aggregation factors.\n\nIs the rationale for commenting on the previous publication clearly described? Yes\n\nAre any opinions stated well-argued, clear and cogent? Yes\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Yes\n\nIs the conclusion balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "13136",
"date": "14 Jan 2025",
"name": "Kazuki Yatsuzuka",
"role": "Author Response",
"response": "Thank you for taking your valuable time to review our paper. Sincerely, Kazuki Yatsuzuka"
}
]
}
] | 1
|
https://f1000research.com/articles/13-1494
|
https://f1000research.com/articles/13-1490/v1
|
06 Dec 24
|
{
"type": "Brief Report",
"title": "Diagnosis of brain death in wistar rats at different levels of death induction",
"authors": [
"Nayara Maria Gil Mazzante",
"Fernanda Zuliani",
"Rogerio Antonio de Oliveira",
"Júlia Soares Bodaneze",
"Giovanna Farina Panebianco",
"Natália Freitas de Souza",
"Fernando Carmona Dinau",
"Paola Alejandra Montenegro Cuellar",
"Nadia Yumi Yamamo dos Santos",
"Ana Beatriz de Souza da Silva",
"Fernanda de Freitas Alves Vieira",
"Natália Camargo Faraldo",
"Gabriela Abreu Botelho",
"Fernanda Barthelson Carvalho de Moura",
"Noeme Sousa Rocha",
"Nayara Maria Gil Mazzante",
"Fernanda Zuliani",
"Rogerio Antonio de Oliveira",
"Júlia Soares Bodaneze",
"Giovanna Farina Panebianco",
"Natália Freitas de Souza",
"Fernando Carmona Dinau",
"Paola Alejandra Montenegro Cuellar",
"Nadia Yumi Yamamo dos Santos",
"Ana Beatriz de Souza da Silva",
"Fernanda de Freitas Alves Vieira",
"Natália Camargo Faraldo",
"Gabriela Abreu Botelho",
"Noeme Sousa Rocha"
],
"abstract": "Objective This study aimed to evaluate hematologic, biochemical, and gasometric parameters in Wistar rats to better understand brain death parameters and reduce early misdiagnoses.\n\nMethods Fifteen adult male Wistar rats (Rattus norvergicus; HanUnib: WH) were randomly distributed into three groups of five animals: the control group (G0) with evaluation performed before brain death, and two groups (G1 and G2) with brain death induced at different times: immediately after induction (G1) and one hour after induction (G2). Venous and arterial blood samples were taken to perform complete blood count, biochemical, and blood gas assays. Samples were taken at specific times based on the group each rat belonged to.\n\nResults Statistically significant mean values were observed (P<0,05) for segmented cells (G1>G2 and G0>G2), monocytes (G2>G1 and G0>G1), creatinine (G2>G0), aspartate aminotransferase (G1>G0), potassium (G2>G0), and bicarbonate (G0>G1).\n\nDiscussion Furthermore, brain death showed a unique response in each organism, complicating its precise determination even more.",
"keywords": [
"brain death",
"hematologic analysis",
"Wistar rats"
],
"content": "Introduction\n\nBrain death (BD), the complete and irreversible loss of brain function, is a complex process characterized by an inflammatory state leading to cellular and molecular disturbances that alter the physiology and biochemistry of the organic system.1 However, criteria for determining BD vary among countries, each having national laws or guidelines, resulting in a lack of standardization. In 50% of countries, clinical examination is sufficient to determine BD, whereas the other 50% require complementary tests.2\n\nCurrently, the American Association of Neurology (AAN) defines BD with three cardinal signs: interruption of brain functions, including the brainstem, coma or unresponsiveness, and apnea.3 In Brazil, social changes and advancements in medicine led the Federal Council of Medicine (CFM) to update the criteria for diagnosing BD in 2017, with Resolution No. 2,173 of November 23, replacing No. 1,408/97. The changes included specific physiological prerequisites for patients, requirements for doctors to provide care before diagnosing BD, the necessity of complementary tests, and specific training for doctors making this diagnosis.4,5\n\nDetermining the moment of BD is complicated by significant complex pathophysiological changes involving excitation of the sympathetic nerves, hormonal imbalance, hemodynamic instability, and metabolic disorders with the release of cytokines,6 which peak at alternating times due to the type of reaction and injury severity.7,8 During BD progression, a systemic inflammatory response can worsen, leading to disseminated intravascular coagulation mediated by inflammatory mediators from the ischemic brain, ischemic reperfusion injury, metabolic changes during the catecholamine storm, and an inadequately restored cardiovascular state. This also produces sudden changes in blood pressure, hypoxemia, hypothermia, coagulopathy, and electrolyte and hormonal disorders.9,10\n\nMore studies are needed to accurately determine the moment of BD, especially due to the scarcity of data. The literature on BD in animals is even more limited. Given the social importance of animals and the growing demand for scientific data to determine and establish death in animals, this has become an important issue for veterinarians. This importance is underscored by the increase in the animal market (farming, pet market, etc.) and the evolution of veterinary medicine (freelancers, clinics, hospitals, and research centers). Therefore, this study aimed to evaluate the hematological, biochemical, and gasometric parameters in rats, as these can be determinants of BD and help elucidate its concept, reducing errors in early diagnosis.\n\n\nMethods\n\nFifteen Wistar adult male rats (Rattus norvegicus) of the HanUnib: WH line were acquired from the Multidisciplinary Center for Biological Research at the State University of Campinas (CEMIB - UNICAMP). They were housed in the Central Experimental Vivarium of the Experimental Research Unit (UNIPEX) at the Medical School (FMB) of São Paulo State University (UNESP). The rats were kept in polypropylene cages with metal grid covers in a room maintained at 22 °C and 55% humidity under a light-dark cycle. The protocols used in this study are in accordance with the Ethical Principles in Animal Research adopted by the Brazilian College of Animal Experimentation (COBEA) and were approved by the Ethics Committee on the Use of Animals (CEUA) of the Faculty of Medicine (FMB) of UNESP, Botucatu Campus, protocol No. 0259/2018 on 16th January of 2019.\n\nFood and water were provided ad libitum, and environmental enrichment was performed using polyvinyl chloride (PVC) pipes and paper balls during the experimental period. Individual body weights were recorded weekly to monitor hygiene, adjust the number of animals per cage, and ensure their welfare. After an acclimatization period of 2 weeks, the animals were randomly divided into three groups, each with five animals: control group (G0) (n=5), evaluated before BD, and two groups with BD induction, immediately after induction (G1) (n=5) and 1 h after induction (G2) (n=5).\n\nBefore the induction of BD, the animals were anesthetized, initially in an induction box with isoflurane (9–5%) and then with an isoflurane mask (5–2.5%). Intubation was performed using a 14G or 16G catheter, and rats were maintained in the inhalation anesthesia circuit with isoflurane (3–1.5%). Trichotomy and asepsis were performed using chlorhexidine degermante and 70% alcohol in the area of access to the aorta and femoral vein. A 24G catheter was used to access the aorta and femoral vein, and a three-way tap circuit was set up to monitor blood pressure and collect blood for blood gas analysis, along with venous blood collection for blood count and biochemical tests. Animals with mean arterial pressure (MAP) >70 mmHg were used for hematological, biochemical, and hemogasometric parameters. Those without stable MAP were excluded from the experiment.\n\nBlood samples were collected from each animal according to their respective group timings: G0 at time 0 (M0, before BD), G1 at time 1 (M1, shortly after BD induction), and G2 at time 2 (M2, 1 h after BD induction). Venous blood samples were drawn from the femoral vein into 0.5 ml ethylenediaminetetraacetic acid (EDTA) tubes and refrigerated (6–10 °C) for subsequent erythrogram examination (including red blood cells [RBC], hemoglobin [Hb], hematocrit [HCT], mean corpuscular volume [MCV], mean corpuscular hemoglobin concentration [MCHC], mean corpuscular hemoglobin [MCH], total plasma protein [TPT], red cell distribution width [RDW], and platelets) and leukogram (covering total leukocytes, neutrophils, segmented, lymphocytes, eosinophils, and monocytes).\n\nProcessing was performed using a Hemacounter 60-RT 7600 hematological analyzer (Hemogram, China). Hematocrit was determined by centrifuging microhematocrit samples at 12,000 rpm for 5 min. Platelet counts were performed manually by diluting 20 μL of blood in 2 mL of Brecher solution and counting in a Neubauer chamber. The differential leukocyte count was executed on panotype-stained blood smears (Laborclin) under an optical microscope with immersion (1,000× magnification).\n\nThe biochemical examination was conducted using the BS200E Analyzer (Mindray, Brazil). Venous blood samples from the femoral vein were collected in dry tubes, refrigerated (6–10 °C), and centrifuged at 2,500 rpm for 5 min. This process was followed by analyzing urea, creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum total protein (TP), albumin, globulin, creatine kinase (CK), and CK-MB.\n\nBlood gas analysis was performed using the ABL80 Flex Analyzer - BASIC Version (RADIOMETER). Arterial blood samples were collected from the aortic artery in 1 mL heparinized syringes (volume collected 0.7 mL), immediately packed in a styrofoam container with crushed ice, and analyzed for blood gases (pH, pCO2, and pO2), electrolytes, and metabolites (Na+, K+, Ca2+, Cl-, Lac), and derived values (HCO3 and sO2).\n\nBD induction followed the protocol described by Esmaeilzadeh et al.10 A Fogarty 14G catheter (Baxter Health Corp., CA, USA) was inserted via frontolateral trepanation into the skull using a surgical drill. Intracranial pressure (ICP) was increased by slowly inflating with 400–700 μL of saline. The catheter balloon inflation began with 100 μL of saline solution, and after 1 min, an additional 100 μL of solution was added. This procedure was repeated until the absence of corneal reflexes confirmed the BD, maximally dilated fixed pupils and 60 s apnea.\n\nFollowing BD confirmation, all animals had their body temperature maintained using a thermal mattress, and blood pressure (BP) and heart rate (HR) were continuously monitored with a multiparameter monitor, adjusted according to the respective group. Animals in the BD-induced groups were supported with mechanical ventilation after anesthesia withdrawal. After BD, the animals received a heated infusion of sodium chloride 0.9% supplemented with potassium chloride at a rate of 3–5 mL/kg/h, along with dopamine infusion (5–15 mcg/kg/min), with bolus administration as needed, to conclude animals’ euthanasia.\n\n\nResults\n\nIn the comparison among G0, G1, and G2, no statistically significant differences (P<0.05) were observed in the mean values of RBC, Hb, HCT, MCV, MCHC, MCH, TPP, RDW, and platelets among the experimental animals ( Table 1, Figures 1 and 2).\n\nDifferences in group least squares means, adjusted for multiple comparisons - Tukey-Kramer of the variables.\n\nNotably, animals in G1 exhibited thrombocytopenia. In the leukogram ( Table 2), comparisons among G0, G1, and G2 regarding total leukocytes, segmented leukocytes, lymphocytes, eosinophils, and monocytes from the experimental animals revealed variations in segmented leukocytes and monocytes (p<0.05) (Figure 3).\n\nDifferences in group least squares means, adjusted for multiple comparisons - Tukey-Kramer of the variables.\n\n* Substantial statistical difference (when p<0.05).\n\nThe biochemical tests ( Table 3) compared G0, G1, and G2 regarding urea, Cr, ALT, AST, ALP, GGT, serum TP, albumin, globulin, CK, and CK-MB from the experimental animals (Figure 4). Only Cr and AST exhibited variations in their values.\n\nDifferences in group least squares means, adjusted for multiple comparisons - Tukey-Kramer of the variables.\n\n* Substantial statistical difference (when p<0.05).\n\nOverall, blood gas analysis ( Table 4) showed that most animals in all groups had low hydrogen potential (pH) levels, increased oxygen partial pressures (PaO2), and carbon dioxide partial pressures (PaCO2).\n\nIn some animals, bicarbonate (HCO3) levels were decreased, and the oxygen saturation index (sO2) and lactate values tended to increase. Moreover, sodium levels showed a tendency to increase in most animals, potassium increased in only one, calcium decreased uniformly across all, and chloride tended to rise in the majority.\n\nIn the bivariate analysis, the initial analysis of the nine erythrogram variables in group 0 using the Spearman test showed positive correlations with hemoglobin (Hb), platelets, mean corpuscular volum (MCV), and mean corpuscular hemoglobin (MCH) ( Tables 5 and 6).\n\n* Substantial statistical difference (when p<0.05).\n\n\nDiscussion\n\nThe meticulous control and interpretation of laboratory test changes are intrinsic to diagnosing BD.11,12 Individual examination within each group revealed a tendency towards polycythemia in most animals, particularly notable in G2, consistent with findings from Fiocruz.13 This can be explained by hypoxemia resulting from BD, leading to secondary absolute polycythemia. One subject in G1 showed anemia and hypoproteinemia. One study found hemoglobin and hematocrit concentrations also decreased after BD induction.7 There were also animals in this group that showed thrombocytopenia. Another research revealed 38.5% of organ donors exhibited anemia and 30.8% had thrombocytopenia.28 This phenomenon is attributed to common coagulation disorders following BD, driven by factors such as thromboplastin release, damaged brain tissue fibrinogen release, disseminated intravascular coagulation (DIC), and platelet and coagulation factor consumption due to fluid resuscitation volumes.12\n\nRegarding the analysis of variables in the leukogram examination, the reduction in segmented neutrophils in G2 may be related to increased bone marrow immunosuppression 1 h after BD. An increase in the number of circulating hematopoietic precursor cells, followed by bone marrow dysfunction, has been observed in patients with severe trauma, hemorrhagic shock, or burns. Stroke induces systemic inflammatory response and subsequent immunosuppression.14,15\n\nEvaluating the animals in each group individually, two animals (A6 and A11) in G1 and G2, respectively, presented leukocytosis. This change is justified by the inflammatory state resulting from the BD process, which activates inflammatory mediators like thromboxanes and leukocyte factors. Among the potential human donors, 66.2% had leukocytosis.16,17 Conversely, Menegat and Sannomiya observed BD-induced leukopenia in rats, resulting in a reduction in lymphocytes, monocytes, and granulocytes.18\n\nThe difference in Cr values between G0 and G2 in this study may be associated with renal function failure due to hemodynamic instability and hypotension, leading to decreased perfusion.19 Another factor that can affect the kidneys and cause a sudden elevation of plasma Cr, which is widely used as an indicator of acute renal failure and changes in diuresis volume, is rhabdomyolysis.20 In this study, most of the gas tests presented an acid-base imbalance. Most animals tended towards respiratory acidosis, and some presented metabolic acidosis. These disorders are associated with an increased risk of organ and system dysfunction, and metabolic acidosis is an indicator of unfavorable clinical outcomes.21,22\n\nIn BD, gasometry values vary considerably, as the lungs are among the first organs to suffer changes in the body. The lungs seek to compensate and preserve a physiologically acceptable pH when the renal ability to maintain homeostasis is lost.23 However, the lung tissue can be affected by pathophysiological and endocrine changes and the inflammatory reactions caused by BD.24 Additionally, perfusion-ventilation imbalance and hypoxemia are the main manifestations of pulmonary changes due to intense adrenergic discharge, leading to increased venous return to the right ventricle consequently increased pulmonary flow. Along with elevated left atrial pressure from intense peripheral vasoconstriction, this results in increased capillary hydrostatic pressure, promoting capillary rupture, interstitial edema, and alveolar hemorrhage.25\n\nAbnormal partial oxygen pressure promotes the release of tumor necrosis factor-alpha and IL-1 beta, which are inflammatory cytokines that mediate lung lesions.20 According to Mascia et al.19 and Botha et al.,6 30–45% of potential donors develop lung injury, with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) being the most frequent. Nogueira and Pereira25 observed that 69.2% of patients had hyperoxia due to oxidative stress in the clinical picture of BD. In this study, lactate levels tended to increase. This is mainly due to altered energy metabolism, where excessive prolongation of anaerobic metabolism overcomes the body’s ability to remove lactate, leading to metabolic acidosis, which can become severe and cause fatigue, even when buffering mechanisms are well-developed.26,27 According to Hodgson and Rose, an anaerobic threshold is commonly reached when lactate.28 concentration is between 2–4 mmol/L. In our study, higher lactate levels were observed.\n\nIn most animals, hypernatremia was observed, and an increase in potassium was seen in only one animal, contradicting Westphal et al.,19 who observed hyperkalemia and hypomagnesemia as common disorders associated with BD, potentially leading to arrhythmia. Additionally, calcium decreased in all animals, whereas chlorine levels tended to increase in most cases. Hypernatremia was observed in most animals, and an increase in potassium was seen in only one animal. This contradicts Westphal et al.,19 be related to progressive dysfunction of the hypothalamic-pituitary axis after BD and, in 80% of cases, the development of diabetes insipidus, which results in a decline in circulating antidiuretic hormone.29 The polyuria resulting from this endocrine/metabolic change can lead to serious electrolyte disorders, such as hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hypomagnesemia.13 In a study by Vasconcelos et al. with possible human donors, 47.7% had hypernatremia, similar to the values obtained in this study.30\n\nTherefore, this study recognizes and highlights the deleterious effects caused by BD, noting that these effects are multiple and cause various complications in the body, so an evaluation using different combined analyses is important, as shown in this study, to also diagnose different critical diseases prior to the brain death itself. Early detection is important to avoid progressive somatic deterioration and ensure better organ function.30,31 The experimental model used in this study, which is interesting for evaluating a short period of time, did not produce more significant results for many variables. The speed of diagnosing BD may not lead to major changes in tests within 1 h after BD. Additionally, the number of animals (n) used was a limiting factor. In conclusion, BD showed a unique response in each organism, complicating its precise determination even more.\n\n\nEthics\n\nWe confirm that all efforts were made to ameliorate suffering of animals applying the rules settled to animal pain management and suffering in the “Brazilian Guide to Good Animal Euthanasia Practices” (available online in: https://www.cfmv.gov.br/guia-brasileiro-de-boas-praticas-para-a-eutanasia-em-animais/comunicacao/publicacoes/2020/08/03/#1) dictated by the Brazilian Federal Council of Veterinary Medicine (CFMV). Ethical Principles in Animal Research adopted by the Brazilian College of Animal Experimentation (COBEA) and were approved by the Ethics Committee on the Use of Animals (CEUA) of the Faculty of Medicine (FMB) of UNESP, Botucatu Campus, protocol No. 0259/2018 on 16th January 2019.",
"appendix": "Data availability\n\nFigshare: Parâmetros hematológicos, gasométricos e bioquímicos na indução da morte encefálica em ratos Wistar, DOI: https://doi.org/10.6084/m9.figshare.27586602.v632\n\nThis project contains the following underlying data:\n\n• PARÂMETROS HEMATOLÓGICOS, GASOMÉTRICOS E.docx\n\n• Underlying data spreadsheet.xlsx\n\n• IACUC\n\n• mazzante_nmg_dr_bot_sub-english.docx\n\n• Underlyingdataspreadsheet-english.xlsx\n\n• ARRIVE Checklist\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Arrive checklist for ‘ Parâmetros hematológicos, gasométricos e bioquímicos na indução da morte encefálica em ratos Wistar’, DOI: https://doi.org/10.6084/m9.figshare.27586602.v6\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe thank the School of Veterinary Medicine and Animal Science of São Paulo State University for their support and encouragement during this study.\n\n\nReferences\n\nAbram MB, Fox RC, Garcia-Palmier M, et al.: Defining death: medical, legal and ethical issues in the determination of death. Washington, DC: Georgetown University; 1981. Accessed January 22, 2019. Reference Source\n\nCiterio G, Crippa IA, Bronco A, et al.: Variability in brain death determination in Europe: looking for a solution. Neurocrit. Care. 2014; 21: 376–382. PubMed Abstract | Publisher Full Text\n\nWijdicks EFM, Varelas PN, Gronseth GS, et al.: Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010; 74: 1911–1918. PubMed Abstract | Publisher Full Text\n\nSeção 1: Brasil. Resolução n°2. 2017;173, de 23 de novembro de 2017. Diário Oficial da União, Poder Executivo, Brasília, DF:50–275.\n\nCFM - Conselho Federal de Medicina: Resolução n° 1.480/1997. Define Critérios para Diagnóstico de Morte Encefálica. Brasília (DF): CFM; 1997. Accessed August 17, 2016. Reference Source\n\nChen L, Feng X, Wang Y, et al.: Study of the Role of Transforming growth factor β-1 in Organ Damage Protection in Porcine Model of Brain Death. Transplant. Proc. 2016; 48: 205–209. PubMed Abstract | Publisher Full Text\n\nEsmaeilzadeh M, Sadeghi M, Galmbacher R, et al.: Time-course of plasma inflammatory mediators in a rat model of brain death. Transplant. Immunol. 2017; 43-44: 21–26. Publisher Full Text\n\nMurugan R, Venkataraman R, Wahed AS, et al.: Increased plasma interleukin-6 in donors is associated with lower recipient hospital-free survival after cadaveric organ transplantation. Crit. Care Med. 2008; 36: 1810–1816. PubMed Abstract | Publisher Full Text\n\nTuttle-Newhall JE, Collins BH, Kuo PC, et al.: Organ donation and treatment of the multi-organ donor. Curr. Probl. Surg. 2003; 40: 266–310. Publisher Full Text\n\nAgnolo CM, de Freitas RA , Almeida DF, et al.: Morte encefálica: assistência de enfermagem. Braz. J. Transplant. 2010; 13: 1258–1262. Publisher Full Text\n\nLima CM, Lima AK, Melo MGD, et al.: Valores de referência hematológicos e bioquímicos de ratos (Rattus novergicus linhagem Wistar) provenientes do biotério da Universidade Tiradentes. Sci. Plena. 2014; 10: 1–9.\n\nFiocruz: Centro de Criação de Animais de Laboratório da Fundação Oswaldo Cruz. Resultado de exames hematológicos para ratos Wistar - Laudo Clínico. Portal da Fundação Oswaldo Cruz; 2004. Accessed January 22, 2019. Reference Source\n\nNogueira EC: Captação de órgãos em Sergipe e fatores associados à efetivação de potenciais doadores; 2008. 103f. Dissertação (Mestrado) - Universidade Federal de Sergipe. Aracaju.\n\nBadami CD, Livingston DH, Sifri ZC, et al.: Hematopoietic progenitor cells mobilize to the site of injury after trauma and hemorrhagic shock in rats. J. Trauma. 2007; 63: 596–602. discussion 600. PubMed Abstract | Publisher Full Text\n\nDenes A, McColl BW, Leow-Dyke SF, et al.: Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses. J. Cereb. Blood Flow Metab. 2011; 31: 1036–1050. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRech TH, Rodrigues Filho EM: Manuseio do potencial doador de múltiplos órgãos. Rev. Bras. Ter. Intensiva. 2007; 19: 197–204. PubMed Abstract\n\nVasconcelos Q, Freire ILS, Araújo RO, et al.: Avaliação laboratorial de potenciais doadores de órgãos e tecidos para transplantes. Rev. Rene. 2014; 15: 273–281.\n\nMenegat L, Sannomiya P: Estudo dos processos de mobilização. Ativação e Apoptose Das Células da Medula Óssea em Modelo de Morte Encefálica em Ratos; 2016. 90f. Tese (Doutorado) - Universidade de São Paulo. São Paulo.\n\nWestphal GA, Caldeira Filho M, Vieira KD, et al.: Diretrizes para manutenção de múltiplos órgãos no potencial doador adulto falecido. Parte II. Ventilação mecânica, controle endócrino metabólico e aspectos hematológicos e infecciosos. Rev. Bras. Ter. Intensiva. 2011b; 23: 269–282. PubMed Abstract | Publisher Full Text\n\nNogueira EC, Pereira CU: Potencial para obtenção de órgãos em um hospital de urgência de Sergipe. Braz. J. Transplant. 2007; 10: 756–761. Publisher Full Text\n\nBarbosa MBG, Alves CAD, Filho HQ: Avaliação da acidose metabólica em pacientes Graves: método de Stewart-Fencl-Figge versus a abordagem tradicional de Henderson-Hasselbalch. Rev. Bras. Ter. Intensiva. 2006; 18: 380–384. Publisher Full Text\n\nRocco JR: Diagnóstico dos distúrbios do metabolismo ácido-base. Rev. Bras. Ter. Intensiva. 2003; 15: 184–192.\n\nViegas CA: Gasometria arterial. J. Pneumol. 2012; 28: 233–238.\n\nMascia L, Sakr Y, Pasero D, et al.: Extracranial complications in patients with acute brain injury: a post-hoc analysis of the SOAP study. Intensive Care Med. 2008; 34: 720–727. PubMed Abstract | Publisher Full Text\n\nGuetti NR, Marques IR: Assistência de enfermagem ao potencial doador de órgãos em morte encefálica. Rev. Bras. Enferm. 2008; 61: 91–97. PubMed Abstract | Publisher Full Text\n\nBeard LA, Hinchcliff KW: Effect of NaCl and NaHCO3 on serum ionised calcium and blood gas status during sprinting. Equine Vet. J. 2002; 34: 519–523. Publisher Full Text\n\nWestphal GA, Caldeira Filho M, Vieira KD, et al.: Diretrizes para manutenção de múltiplos órgãos no potencial doador adulto falecido: Parte I. Aspectos gerais e suporte hemodinâmico. Rev. Bras. Ter. Intensiva. 2011; 23: 255–268. PubMed Abstract | Publisher Full Text\n\nHodgson DR, Rose RJ: The athletic horse: principles and practice of equine sports medicine. 1st ed.Philadelphia: W. B. Saunders Company; 1994; 245–258.\n\nHowlett TA, Keogh AM, Perry L, et al.: Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy. Transplantation. 1989; 47: 828–833. PubMed Abstract | Publisher Full Text\n\nVasconcelos Q, Freire ILS, Araújo RO, et al.: Avaliação laboratorial de potenciais doadores de órgãos e tecidos para transplantes. Rev. Rene. 2014; 15: 273–281.\n\nDa Silva JRF, Silva MHM, Ramos VP: Familiaridade dos profissionais de saúde sobre os critérios de diagnósticos de morte encefálica. Enferm. Foco. 2010; 1: 98–103. Publisher Full Text\n\nBarthelson Carvalho de Moura F, Maria Gil Mazzante N, Rocha NS: Parâmetros hematológicos, gasométricos e bioquímicos na indução da morte encefálica em ratos Wistar. figshare. 2024 [cited 2024Nov22]. Reference Source"
}
|
[
{
"id": "347400",
"date": "17 Dec 2024",
"name": "Chiara Lazzeri",
"expertise": [
"Reviewer Expertise organ procurement and transplantation",
"cardiac arrest",
"ECMO",
"respiratory failure",
"critical care echocardiography"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe topic is quite interesting. The main limitation of the present study is the small number of animals included. This should be addressed in the discussion section. Major issues can be raised: a) in the discussion section each altered parameter is described and discussed. Regarding polycytemia, other hypothesis should be considered, especially volemia b) in regard to coagulation disorders, Authors should add other hypothesized mechanism(s), including the cause of brain death (i.e. trauma) c) what about treatment of brain death d) the Authors should better elucidate the novelty of their investigation in respect to existing evidence on this topic\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1490
|
https://f1000research.com/articles/13-119/v1
|
19 Feb 24
|
{
"type": "Review",
"title": "Enter the Matrix: Fibroblast-immune interactions shape ECM deposition in health and disease.",
"authors": [
"Anthony Altieri",
"Grace V. Visser",
"Matthew B. Buechler",
"Anthony Altieri",
"Grace V. Visser"
],
"abstract": "Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function. In this review, we will highlight recent studies which elucidate the mechanisms by which fibroblast-derived ECM factors (e.g., collagens, fibrillar proteins) regulate ECM architecture and subsequent immune responses, with a focus on macrophages. As examples of fibroblast-derived ECM proteins, we examine Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Transforming Growth Factor-β-inducible protein (TGFBI), also known as BIGH3. We address the need for investigation into how diverse fibroblast populations coordinate immune responses by modulating ECM, including the fibroblast-ECM-immune axis and the precise molecular mediators and pathways which regulate these processes. Finally, we will outline how novel research identifying key regulators of ECM deposition is critical for therapeutic development for fibrotic diseases and cancer.",
"keywords": [
"Fibroblasts",
"Fibroblast heterogeneity",
"Extracellular Matrix (ECM)",
"Immunology",
"Macrophages",
"BigH3",
"Cthrc1"
],
"content": "Introduction\n\nFibroblasts orchestrate ECM deposition in steady state and disease: Fibroblasts are non-hematopoietic mesenchymal stromal cells which are found in all tissues, regulate tissue structure, and influence the phenotype and localization of tissue resident cell types.1–3 As a result, fibroblasts play a critical role in tissue homeostasis and tissue repair. Fibroblasts accomplish these functions in part by producing and secreting extracellular matrix (ECM) proteins, which alter the structure and composition of the composite tissue ECM.3 Here, the ECM refers to the diverse network of proteins that generates the three-dimensional structure of tissues.4–6 In addition, fibroblasts secrete a variety of molecules, including cytokines and chemokines, which can bind the ECM to influence immune cell function and recruitment.2,3,7\n\nUnder homeostatic conditions, fibroblast-derived ECM proteins provide essential support to resident cells and tissues. However, dysregulation of the ECM can contribute to pathogenic outcomes, including fibrosis. When tissues are injured, local tissue fibroblasts become activated and increase their contractility, secretion of inflammatory mediators, and synthesis of ECM components.3,8 These changes initiate the wound healing response.1 When damage is limited and non-repetitive, wound healing is efficient, a transient increase in the deposition of ECM components transpires to facilitate the restoration of functional tissue architecture. However, when injury is repetitive or severe such as in chronic inflammatory diseases, ECM components continue to accumulate, which can lead to structural alterations of the ECM, disruption of tissue architecture, organ dysfunction, and ultimately, organ failure.1,4 In these situations, fibroblasts produce excessive ECM, and changes to the fibrillar collagen network result in pathological tissue stiffness, loss of mechanical compliance, and loss of tissue function.2 As a result, fibrotic disease affects almost all organ systems and is a contributing factor in 45% of all deaths in high income countries.8,9 Therefore, an appreciation of the interconnectivity between fibroblasts, the ECM, and immune cells is required to understand the causality of fibrotic disease.3 Here we integrate the current understanding of the fibroblast-ECM-immune axis and review the evidence supporting current models defining fibroblast-immune interactions. These studies serve as the basis for future exploration into immune cell regulation by fibroblast-derived ECM molecules.\n\nECM form & function: The ECM is a dynamic 3-dimensional network of more than 300 different core proteins and matrix-modifying enzymes (often referred to as the matrisome).5,6,10 These components are in part produced and assembled by fibroblasts and may either be long lived or transient, making ECM dynamic and sensitive to local and systemic changes.2 Components of the ECM include collagens, proteoglycans (PGs), glycosaminoglycans (GAGs), elastin and elastic fibers, laminins, fibronectin, mucus and other proteins and glycoproteins, such as matricellular proteins.2,4,5 The diversity of proteins in these functional groups is immense. For example, there are approximately 28 types of collagens, molecules which provide structural support to tissues. These components may also combine for additional diversity. For example, fibril-forming collagens have abilities to form covalent cross-links and create matrix structures and include collagens I, II, III, V, and XI. These ECM components have a variety of disparate functions while providing architectural support to tissues. For example, collagens provide tissue strength and resilience, PGs form hydrated gels which cushion tissues, and mucus protects barrier surfaces.2,4 In addition, these components contribute to fundamental processes for tissue development, including cell proliferation, survival, migration, differentiation, autophagy, and angiogenesis.4 These concepts have been reviewed extensively elsewhere.4\n\nThere are a variety of other fibroblast-derived molecules and enzymes which modify ECM structure and regulate their degradation, such as matrix metalloproteinases (MMPs).1 Moreover, fibroblasts produce molecules which bind ECM components to alter the composition and function of ECM-resident cells. For example, fibroblasts produce and secrete cytokines, chemokines, and growth factors, which are an implicit part of immune cell regulation.2 It is also notable that immune cells are often connected to the unique matrix surrounding them, and every cell to varying degrees is coated in a glycocalyx, a complex network of sugar rich molecules either free or bound to proteins and/or lipids.2,11 As a result, the ECM regulates the signaling, functions, properties, and morphology of residing immune cells in addition to providing structural support for tissues.4 These properties may be altered in a tissue-specific manner.3 Specific ECM phenotypes configure the different tissues, including epithelial, muscle, connective, and more to meet the requirements for optimal tissue function.4 Here, the prevalence of different, tissue-specific heterogeneous fibroblast subsets with unique gene expression signatures can further alter the ECM and therefore tissue characteristics.12 Finally, fibroblasts have unique functions depending on disease states. Fibroblasts that become activated due to repeated injury and chronic inflammation are typically referred to as myofibroblasts and have altered gene expression profiles that drive fibrotic disease. Below, we highlight critical immune-facing functions of fibroblast- and myofibroblast-derived ECM components in steady-state and disease.5\n\nFibroblast derived cytokines and chemokines decorate the ECM to influence fibroblast-macrophage interactions. Fibroblasts produce cytokines and chemokines which bind the ECM and are critical for immune cell recruitment and function in steady-state and disease2,13 (Figure 1). For example, multiple in vitro and tissue-restricted in vivo studies have demonstrated that a relationship exists between fibroblasts and macrophages, an innate immune cell which orchestrates long-lived adaptive immune responses through phagocytosis, antigen presentation, and immunological mediator secretion.13 Fibroblasts and macrophages are found in almost all tissues and multiple studies indicate that fibroblast-derived CSF1, which can decorate the ECM, is a critical factor for macrophage survival. Using in vitro studies, Zhou et al. demonstrated that macrophages and fibroblasts form stable cell circuits that are resistant to perturbations and that cell-to-cell contact increased cell circuit survival because of local exchange of growth factors, including CSF1.14 In addition, in vivo studies have demonstrated that fibroblastic reticular cells (FRC) are required to establish the lymph node (LN) macrophage niche. D’Rozario et al. demonstrated that genetic ablation of FRC using a genetic tool in which Chemokine (C-C motif) ligand 19 (Ccl19)-expressing cells could be depleted using diphtheria toxin resulted in rapid loss of monocytes and macrophages from LN in two separate in vivo models.15 Moreover, single-cell RNA sequencing (scRNA-seq) of murine brachial lymph nodes revealed that FRC subsets broadly expressed master macrophage regulator CSF1 and functional assays containing purified FRC and monocytes showed that CSF1R signaling was sufficient for macrophage survival.15 Comparative analysis demonstrated these effects were conserved between mice and humans.15\n\nFibroblasts use several mechanisms to recruit macrophages to the ECM. Fibroblast-derived cytokines and chemokines bind the ECM and enhance accumulation of ECM-associated macrophage. Fibroblast contraction remodels collagen fibers to enhance macrophage recruitment. Fibroblasts secrete MMPs to cleave ECM- and ECM bound proteins to enhance macrophage accumulation in the ECM.\n\nMonocytes, which can give rise to macrophages, have also been shown to require stromal cell derived CSF1. Emoto et al. demonstrated that CSF1 produced by sinusoidal endothelial cells was required for the survival of Ly6C- monocytes. Conversely, CSF1 produced by both endothelial and Lepr+ perivascular stromal cells were required for the survival of Ly6Chi monocytes.16 Taken together, these studies demonstrated that macrophage survival in specific tissues is regulated by stromal-derived CSF1.\n\nAs different tissue-specific fibroblast subsets can produce different levels of CSF1,17 additional studies are required to delineate which subsets are critical for macrophage homeostasis. Moreover, the functional role of macrophages sustained by fibroblast-derived CSF1 in disease requires further study. Previous work by Zhu et al. has demonstrated that a pharmacologically induced CSF1 blockade in mouse pancreatic tumour models results in increased antigen presentation and productive antitumour T cell responses.18 Despite this, the precise contribution of fibroblast-derived CSF1 in antitumour immunity is not well understood. Furthermore, the functional contributions of these macrophages in chronic inflammation and cancer also require subsequent study.\n\nIn addition to cytokines, activated fibroblasts, including myofibroblasts, produce ECM-binding macrophage chemoattractants indicating that fibroblasts are capable of recruiting monocytes and macrophages during injury, infection, and inflammation.19,20 For example, the bacterial ligand lipopolysaccharide (LPS), which activates toll-like receptor (TLR)4, has been shown to enhance expression of macrophage chemoattractants Ccl2 and Ccl4 in myofibroblast progenitor cells in a mouse model of liver fibrosis.19 As LPS-mediated TLR4 activation occurs widely in anti-bacterial immunity, this suggests that fibroblasts can respond to pathogen-associated molecular patterns (PAMP) to recruit immune cell subsets, including macrophages, in a variety of anti-infective contexts. However, the role of fibroblast-mediated macrophage recruitment in additional anti-infective immune responses, as well as chronic inflammation, requires future investigation.\n\nFibroblasts influence macrophage migration through mechanical cues. Previous studies have also demonstrated that fibroblasts can influence macrophage dynamics by regulating the physical mechanics of the ECM (Figure 1). Pakshir and colleagues showed that contractile myofibroblasts drive mechanical cues through local remodeling of collagen fibers resulting in increased macrophage migration directly towards myofibroblasts using 3D collagen gels in vitro.21 Migration occurred independently of chemotaxis and required macrophage-mediated attachment to collagen via the α2β1 integrin and stretch-sensitive ion channels.21 Similar observations have been described in several fibroblast-like cells,22–24 indicating the importance of these biomechanical mechanisms for cell communication and movement across tissues.\n\nFibroblast-derived matrix metalloproteinases degrade ECM proteins to enhance macrophage recruitment. Matrix metalloproteinases (MMPs) are a family of enzymes which degrade ECM proteins. These enzymes are either secreted or attached to cell surfaces, confining their activity to membranes, secreted proteins, or proteins within the extracellular space.25 MMPs have a complex role in regulating inflammation by acting on a multitude of immunological mediators, including antimicrobial host defense peptides, cytokines, chemokines, and ECM proteins as reviewed in detail here.25 In addition, matrix metalloproteinases are enhanced in stromal cells, including fibroblasts, in response to pro-inflammatory cytokines.26,27 As a result, modulation of the ECM during inflammation alters immune cell migration and ECM resident cell types, including macrophages (Figure 1). For example, Shubayev et al. demonstrated that TNF-α-mediated MMP9 (also known as gelatinase B) production enhances macrophage recruitment in a model of peripheral nerve injury.28 Gong et al. demonstrated that mice deficient for the ECM-bound protease plasminogen (Plg) had decreased trans-ECM macrophage migration and decreased MMP9 activation.29 In addition, the authors demonstrated that MMP9 administration to Plg deficient mice resulted in increased macrophage accumulation in the ECM,29 suggesting that Plg activates MMP9 to increase ECM resident macrophages. Moreover, Tan et al. demonstrated that MMP9 can also cleave the ECM protein osteopontin (OPN) to enhance macrophage recruitment in a mouse model of renal fibrosis.30 Despite this, additional studies are required to understand how MMP-mediated degradation of other ECM components alters immune cell recruitment and fibrotic disease development.\n\n\nFibroblast heterogeneity dictates ECM deposition\n\nIn addition to fibroblast-derived components, immune-derived cytokines and growth factors shape play a critical role in fibrosis and fibrotic diseases by altering fibroblast heterogeneity and therefore ECM deposition. Below, we highlight the relationship between inflammation, fibroblast heterogeneity, and ECM deposition (Figure 2). Moreover, we outline the role that modulators of growth factor signaling play in shaping ECM deposition and subsequent fibrotic disease.\n\nFibroblasts become activated in response to repetitive injury, chronic inflammation or can be activated by cytokines to enhance the production of ECM components. As a result, heterogeneous fibroblast subsets can alter the physical properties of the ECM, as well as ECM-resident cells. In addition, fibroblasts produce molecules including TGFBI/BIGH3 and CTHRC1 which play multifaceted roles in regulating fibroblast-mediated ECM deposition.\n\nImmunological and inflammatory cues dictate fibroblast heterogeneity and ECM deposition. ECM composition is regulated by diverse fibroblast subsets in health and disease. Here, pro-inflammatory cytokines, growth factors, and other ECM proteins can convert fibroblasts into myofibroblasts.31 Relative to fibroblasts found in unperturbed tissues, myofibroblasts exhibit increased expression of contractile protein genes, such as alpha smooth muscle actin (Acta2)32 as well as other of ECM proteins.33 For example, fibrotic cells are heterogeneous and distinct between uninjured and injured skin. Building on previous experiments in mice which demonstrated that embryonic mesenchymal precursors expressing Engrailed (En1) or Delta-like homolog 1 (Dlk/Pref1) generate skin fibroblast and adipocyte lineages, Shook et al. demonstrated that the predominant population of ECM-producing myofibroblasts in the skin are adipocyte precursor cells (AP) derived from En1-lineage traced fibroblasts.34 In addition, this study demonstrated that wound bed myofibroblasts upregulated Acta2 and Col1a1 mRNA expression compared to fibroblast populations from uninjured skin.34 Further, the authors compared the transcriptional profiles of 2 major populations of fibrotic mesenchymal cells that are enriched in skin wound beds: APs and CD29high cells. APs had greater expression of ECM components/regulators including collagens Col5a2, Col14a1, as well as matrix metalloproteinases Mmp2, Mmp3, Mmp23, Mmp27. Conversely, CD29high fibroblasts expressed elevated levels of Col6a3, Col7a, Mmp13, and Tnc. Moreover, platelet-derived growth factor C (pdgfc) secreted by CD301b-expressing macrophage triggered the proliferation of APs, but not other myofibroblasts, highlighting the role of immune-derived growth factors in shaping fibroblast heterogeneity.\n\nTransforming growth factor beta (TGF-β) is another major immune-derived growth factor which drives the expression of myofibroblast-associated genes. TGF-β is produced by a variety of cells, including macrophages, under inflammatory conditions and drives myofibroblast activation.13 In the canonical TGF-β pathway, TGF-β targets the TGF-β receptor complex in cells to drive the activation of intracellular kinases, including SMAD2/3, co-SMAD, and SMAD4 to upregulate ECM and myofibroblast-associated genes, such as Col1a1 and Acta2.35,36 In addition, TGF-β can also signal through non-canonical signaling pathways and activate all three mitogen-activated protein kinase (MAPK) pathways and proteins, including extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun-N-terminal kinase (JNK).35 TGF-β-mediated signaling through these pathways may occur in either a Smad-dependent or -independent fashion.35 TGF-β also activates Rho GTPase signaling and the PI3 kinase/Akt pathway.35 As TGF-β is crucial for myofibroblast development and ECM production, modulators of TGF-β-signaling may be co-factors that affect myofibroblast phenotypes and ECM production from these cells. We define co-factors as proteins that are required for optimal signaling of another protein, such as TGF-β.\n\nFibroblast-derived CTHRC1 as a regulator of ECM deposition. Collagen triple helix repeat containing 1 (CTHRC1), a secreted ECM protein, has recently been identified as a critical modulator of ECM protein modulation and wound healing.37,38 Human CTHRC1 contains a N-terminal 30 amino acid hydrophobic signal peptide secretory domain, a short collagen triple helix repeat (CTHR) domain consisting of 12 repeats of the Gly-X-Y motif, and a highly conserved C-terminal domain with similar structure of the globular C1q domain of Collagen VIII.39,40 CTHRC1 is expressed in macrophages, myofibroblasts, endothelial cells as well as mesenchymal-derived cells41 and as a result, CTHRC1 expression occurs in multiple tissues, including the bone,42 the lung,43 and tumours.44\n\nPrevious studies suggest that CTHRC1 modulates TGF-β signaling (Figure 3A). For example, Cthrc1 modulates TGF-β signaling by promoting the degradation of canonical signaling intermediates, including Smad2/3, and has been suggested to influence Wnt and β-integrin signaling to affect cancer cell proliferation and metastasis.41 Guo et al. showed that Cthrc1 modulated β-integrin signaling by enhancing phosphorylation of Focal adhesion kinase (FAK) to promote metastasis of epithelial ovarian cancer (EOC) cells.45 In fibroblast and smooth muscle cells, CTHRC1 levels are associated with increased cell migration in vitro.46 Other reports suggest that CTHRC1 may negatively regulate TGF-β-mediated signaling pathways. For example, Leclair et al. demonstrated that overexpression of CTHRC1 in smooth muscle cells reduced levels of phosphorylated Smad2/3, which is required for TGF-β-mediated gene expression and collagen production.47 As Cthrc1 expression is enhanced in response to TGF-β in vitro,46 mechanistic evidence suggests that TGF-β and CTHRC1 may act in a negative-feedback loop to limit TGF-β-induced ECM deposition. Due to conflicting reports on the role of CTHRC1 in a disease context, additional studies are required. Future queries delineating the precise relationship between CTHRC1 in TGF-β-mediated signaling and the role of CTHRC1 in a disease context must focus on cell- and tissue-specific mechanisms.\n\n(A) TGF-β signaling enhances production of extracellular matrix proteins, as well as CTRHC1, resulting in negative feedback loop which may limit its own production. Secreted CTHRC1 can bind to collagens and integrins and has been implicated in cancer cell proliferation and migration by influencing Wnt and integrin β signaling pathways. (B) TGF-β signaling enhances BIGH3 production which subsequently binds collagens and integrins. Proposed pathways of BIGH3-mediated collagen production include inactivation of the GPSM2 signaling pathway and activation of Snail, a transcription factor which influences collagen production. Legend: dashed lines represent prospective/predicted interactions.\n\nCTHRC1 has been shown to mark lung myofibroblasts in the context of models of lung fibrosis in murine systems and idiopathic pulmonary fibrosis (IPF) in humans.17,43,48–50 Cthrc1 expression may also distinguish two disease-associated myofibroblast clusters across tissues.17 One disease-associated myofibroblast cluster is marked by the simultaneous expression of Lrrc15 (leucine-rich repeat 15) and Cthrc1 expression, whereas the other is only marked by Cthrc1 and not Lrrc15 expression.17 scRNA-seq-based characterization of collagen-producing cells in fibrotic mouse lungs demonstrated that the Cthrc1+ fibroblast cluster expresses the highest levels of ECM proteins, including Col1a1 and Col3a1.43\n\nTsukui et al. used transgenic mice to track and ablate Cthrc1-expressing fibroblasts in lung fibrosis. Lineage tracing using Ctrhrc1-CreER mice crossed to Rosa26-tdTomato mice demonstrated that Cthrc1-expressing lung fibroblasts expand in a mouse model of bleomycin-induced pulmonary fibrosis. Cthrc1-Cre-ER-labeled cells showed elevated expression of ECM genes, including Col1a1 and Postn (periostin). Further, depletion of Cthrc1-expressing lung fibroblasts using Ctrhrc1-CreER mice crossed to Rosa26-tdTomato and Diphtheria toxin receptor expressing mice attenuated hydroxyproline, a marker of collagen deposition following administration of bleomycin.49 Taken together, these results suggest that Cthrc1 expressing cells drive ECM deposition and may promote fibrosis.\n\nConversely, different studies have demonstrated that CTHRC1 may limit ECM deposition and fibrosis. Global Cthrc1 knock-out (KO) resulted in increased hydroxyproline levels and tissue remodeling in the lungs of mice following bleomycin administration.48 In a mouse model of vascular fibrosis, Cthrc1 was transiently expressed by adventitial fibroblasts following injury and was associated with decreased collagen deposition in cross-sections of carotid arteries.46 The discrepancies between these studies may highlight the cell-, tissue-, and disease-specific role of Cthrc1. As such, further studies are needed to determine the precise role of CTHRC1 in diverse fibrotic diseases. In addition, specific genetic tools, including fibroblast-specific Cthrc1 KO mice or fluorescently-labelled Cthrc1-expressing cells are required to properly assess the pathogenicity of Cthrc1+ myofibroblasts in different tissues and disease models.\n\nFibroblast- and macrophage-derived BIGH3 is associated with increased collagen deposition. Transforming growth factor beta inducible protein (TGFBI), is also known as keratoepithelian,51 and is referred to here as beta-inducible growth hormone 3 (BIGH3) is produced by fibroblasts and macrophages.52 BIGH3 was discovered in 1992 as a gene highly upregulated by A594 lung adenocarcinoma cells following TGF-β stimulation.53 The structure of BIGH3 has not been solved; however, early characterization of this protein using cDNA sequence analysis suggested that it contains a secretory signal peptide, four fasciclin 1 (FAS1) domains that mediate binding to extracellular matrix proteins, such as collagens, and a RGD motif that enables the binding of this protein to integrin receptors.53–55 BigH3 has been shown to be expressed by fibroblasts upon TGF-β exposure56 and by macrophages in ‘M2’ polarization conditions in vitro.57–59 In monocytes, BigH3 is produced following ingestion of apoptotic cells.52 Upon secretion by fibroblasts and macrophages, BIGH3 binds ECM components, such as collagens,60 and subsequently regulates the αvβ5-dependent adhesion and migration of mesenchymal and ectodermal-lineage cells, including fibroblasts, chrondrocytes, osteoblasts, keratinocytes, and endothelial cells.58,59,61\n\nThis gene is also a paralog of periostin (POSTN).62 Studies investigating the role of BIGH3 in disease indicated tissue-specific functions. Schwanekamp et al. demonstrated that BigH3 was enhanced in response to myocardial infarction in the heart. Despite this, cardiac-specific deletion of BigH3 did not alter cardiac disease or fibrosis post-myocardial infarction.63 In the colon, TGF-β signalling plays a major role in promoting fibrotic lesions in inflammatory bowel diseases (IBD).36 Aligned with this BigH3, as well as ECM genes COL1A1, COL1A2, and COL3A1 are upregulated in patients with fibrotic IBD, suggesting that combined BIGH3 and TGF-β signalling may accelerate colon fibrosis.36,64 In the lungs, Ahlfeld et al. demonstrated that BigH3 is elevated in response to lung injury63 and BigH3 KO mice at early ages had documented lung developmental abnormalities, lack of elastin-positive tips, reduced proliferation, and abnormally persistent aSMA myofibroblasts, which resolve by adulthood.65 The authors also demonstrated that lungs in BigH3 deficient mice had reduced elastic recoil and gas exchange efficiency.65 Zhang et al. demonstrated that BigH3 deficient mice had stunted growth in vivo, as well as enhanced proliferation and cyclin D1 expression ex vivo, suggesting that BIGH3 may limit cellular proliferation.66 It remains to be seen if adult animals exhibit these defects or compensatory effects mask phenotypes seen in younger animals.\n\nIn addition to impacting lung development, in vitro studies have demonstrated that BIGH3 can promote collagen deposition in lung fibroblasts.67 Yang et al. found that siRNA-mediated knockdown (KD) of BigH3 in human lung fibroblast cultures resulted in decreased TGF-β- collagen 1 (Col 1) and αSMA production, demonstrating that BIGH3 is necessary to produce these ECM proteins.67 The molecular mechanism by which BIGH3 mediates Col1a1 deposition downstream of TGF-β is unclear. It has been posited based upon in vitro studies using lung fibroblast cell lines that BIGH3 mediates its effects via a multi-part mechanism. Briefly, TGF-β first elicits BIGH3 expression, then BIGH3 binds a multitude of integrin receptors, including α1β1,68 α3β1,69,70 αvβ358 or αvβ558 integrin. BigH3 then drives activation of PI3K-signaling70 and increased Snail expression, encoded by Snail1, via downregulation of a Snail negative regulator G-protein signaling modulator 2 (GPSM2).58,67 Aligned with this, Nacu et al. demonstrated that lung fibroblasts stimulated with BIGH3 had increased Collagen 1 protein abundance.52 Taken together, these studies revealed that BIGH3 is both necessary and sufficient to induce collagen production in lung fibroblasts. However, further study is required to characterize the full scope of ECM deposition changes in response to BIGH3.\n\nMechanistic studies indicate that BIGH3 modulates TGF-β-mediated signal transduction pathways (Figure 3B). In addition to studies defining the tissue-specific nature of BIGH3 and the mechanisms of its effect on ECM deposition, further investigation is required into additional roles of BIGH3 in the context of fibroblasts and macrophage spatiality, including mechanical sensing, and/or monocyte/macrophage chemotaxis. As such, cell- and tissue-restricted BIGH3 KO models paired with high-resolution techniques, such as scRNA-seq are required to examine the role that BIGH3 plays in modulating ECM deposition, development, and disease.\n\n\nConclusions\n\nThe interface between fibroblasts, the immune system, and the ECM is wide and complex. As a result, an appreciation that fibroblasts and the immune system act in a finely tuned and integrated system for ECM deposition is required for understanding the biology of fibroblasts, as well as their roles in ECM deposition and fibrotic disease. Current research focus on the relationship between fibroblasts and macrophages. As a result, additional studies are required to determine whether the relationships between fibroblasts and other immune cell subsets can shape ECM deposition or if macrophages are required as an intermediate. Despite this, targeting the fibroblast-ECM-immune axis may provide opportunities to prevent fibrotic disease. For example, defining the mechanism of action of immune-derived ECM modulators, including CTHRC1 and BIGH3, may provide an opportunity to modulate disease-associated myofibroblast development and/or prevent excessive fibrosis. Indeed, an attractive approach to ameliorate TGF-β related fibrosis may be to target potential co-factors or effect modulators within the TGF-β signaling pathway, such as CTHRC1 or BIGH3. It is possible that fibrotic deposition by fibroblasts is akin to opening a safe that requires two keys: one representing TGF-β and the other representing an essential co-factor, such as CTHRC1 or BIGH3 (Figure 4). To this end, we envision that intervention strategies specifically targeting TGF-β signalling cofactors (or the myofibroblasts that produce them) may limit fibrotic disease and prevent off-target effects that are common among current therapies.\n\nThe role, mechanism, and source of cofactors, including CTHRC1 or BigH3 in health and fibrotic disease are not well defined. Further studies are required to determine key aspects of BIGH3 and CTHRC1 biology and how this drives ECM deposition and fibrotic disease in combination with other pro-fibrotic mediators.\n\n\nAuthor contributions\n\nWriting – Anthony Altieri, Grace Victoria Visser, Matthew B Buechler.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nHenderson NC, Rieder F, Wynn TA: Fibrosis: from mechanisms to medicines. Nature. 2020; 587: 555–566. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSutherland TE, Dyer DP, Allen JE: The extracellular matrix and the immune system: A mutually dependent relationship. Science. 2023; 379: eabp8964. Publisher Full Text\n\nDavidson S, et al.: Fibroblasts as immune regulators in infection, inflammation and cancer. Nat. Rev. Immunol. 2021; 21: 704–717. PubMed Abstract | Publisher Full Text\n\nKaramanos NK, et al.: A guide to the composition and functions of the extracellular matrix. FEBS J. 2021; 288: 6850–6912. PubMed Abstract | Publisher Full Text\n\nKular JK, Basu S, Sharma RI: The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering. J. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nTan TK, et al.: Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage. Lab. Investig. 2013; 93: 434–449. Publisher Full Text\n\nDesmoulière A, Geinoz A, Gabbiani F, et al.: Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J. Cell Biol. 1993; 122: 103–111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWnuk D, et al.: Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment. Sci. Rep. 2020; 10: 16492. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLendahl U, Muhl L, Betsholtz C: Identification, discrimination and heterogeneity of fibroblasts. Nat. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee J, et al.: CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors. Exp. Mol. Med. 2016; 48: e261. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuo B, et al.: Collagen triple helix repeat containing 1 (CTHRC1) activates Integrin β3/FAK signaling and promotes metastasis in ovarian cancer. J. Ovarian Res. 2017; 10: 69. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPyagay P, et al.: Collagen Triple Helix Repeat Containing 1, a Novel Secreted Protein in Injured and Diseased Arteries, Inhibits Collagen Expression and Promotes Cell Migration. Circ. Res. 2005; 96: 261–268. Publisher Full Text\n\nLeClair RJ, et al.: Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation. Circ. Res. 2007; 100: 826–833. Publisher Full Text\n\nBinks AP, Beyer M, Miller R, et al.: Cthrc1 lowers pulmonary collagen associated with bleomycin-induced fibrosis and protects lung function. Physiol. Rep. 2017; 5: e13115. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTsukui T, Sheppard D: Tracing the origin of pathologic pulmonary fibroblasts. bioRxiv. 2022; 2022.11.18.517147. Publisher Full Text\n\nBauer Y, et al.: A Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis. Am. J. Respir. Cell Mol. Biol. 2015; 52: 217–231. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuzina IG, et al.: Interleukin-33 Potentiates Bleomycin-Induced Lung Injury. Am. J. Respir. Cell Mol. Biol. 2013; 49: 999–1008. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNacu N, et al.: Macrophages produce TGF-beta-induced (beta-ig-h3) following ingestion of apoptotic cells and regulate MMP14 levels and collagen turnover in fibroblasts. J. Immunol (Baltim., Md: 1950). 2008; 180: 5036–5044.\n\nSkonier J, et al.: cDNA Cloning and Sequence Analysis of βig-h3, a Novel Gene Induced in a Human Adenocarcinoma Cell Line after Treatment with Transforming Growth Factor-β. DNA Cell Biol. 1992; 11: 511–522. Publisher Full Text\n\nKawamoto T, et al.: Structural and phylogenetic analyses of RGD-CAP/βig-h3, a fasciclin-like adhesion protein expressed in chick chondrocytes1The nucleotide sequence data reported in this paper will appear in the DDBJ, EMBL and GenBank nucleotide sequence databases with the following accession number AB005553.1. Biochim. Biophys. Acta (BBA) - Gene Struct. Expr. 1998; 1395: 288–292.\n\nSkonier J, et al.: βig-h3: A Transforming Growth Factor-β-Responsive Gene Encoding a Secreted Protein That Inhibits Cell Attachment in vitro and Suppresses the Growth of CHO Cells in Nude Mice. DNA Cell Biol. 1994; 13: 571–584. Publisher Full Text\n\nLeBaron RG, et al.: βIG-H3, a Novel Secretory Protein Inducible by Transforming Growth Factor-β, Is Present in Normal Skin and Promotes the Adhesion and Spreading of Dermal Fibroblasts In Vitro. J. Invest. Dermatol. 1995; 104: 844–849. PubMed Abstract | Publisher Full Text\n\nGratchev A, et al.: Alternatively Activated Macrophages Differentially Express Fibronectin and Its Splice Variants and the Extracellular Matrix Protein βIG-H3. Scand. J. Immunol. 2001; 53: 386–392. PubMed Abstract | Publisher Full Text\n\nKim J-E, et al.: Identification of motifs in the fasciclin domains of the transforming growth factor-beta-induced matrix protein betaig-h3 that interact with the alphavbeta5 integrin. J. Biol. Chem. 2002; 277: 46159–46165. PubMed Abstract | Publisher Full Text\n\nHanssen E, Reinboth B, Gibson MA: Covalent and non-covalent interactions of betaig-h3 with collagen VI. Beta ig-h3 is covalently attached to the amino-terminal region of collagen VI in tissue microfibrils. J. Biol. Chem. 2003; 278: 24334–24341. PubMed Abstract | Publisher Full Text\n\nBillings PC, et al.: The transforming growth factor-beta-inducible matrix protein (beta)ig-h3 interacts with fibronectin. J. Biol. Chem. 2002; 277: 28003–28009. Publisher Full Text\n\nGibson MA, Kumaratilake JS, Cleary EG: Immunohistochemical and ultrastructural localization of MP78/70 (betaig-h3) in extracellular matrix of developing and mature bovine tissues. J. Histochem. Cytochem.: Off. J. Histochem. Soc. 1997; 45: 1683–1696. PubMed Abstract | Publisher Full Text\n\nMosher DF, Johansson MW, Gillis ME, et al.: Periostin and TGF-β-induced protein: Two peas in a pod? Crit. Rev. Biochem. Mol. Biol. 2015; 50: 427–439. PubMed Abstract | Publisher Full Text\n\nSchwanekamp JA, et al.: TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury. PLoS One. 2017; 12: e0181945. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHaberman Y, et al.: Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn’s Disease. J. Crohn’s colitis. 2020; 14: S127. Publisher Full Text\n\nAhlfeld SK, Wang J, Gao Y, et al.: Initial Suppression of Transforming Growth Factor-β Signaling and Loss of TGFBI Causes Early Alveolar Structural Defects Resulting in Bronchopulmonary Dysplasia. Am. J. Pathol. 2016; 186: 777–793. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang Y, et al.: TGFBI Deficiency Predisposes Mice to Spontaneous Tumor Development. Cancer Res. 2009; 69: 37–44. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang K, et al.: Transforming growth factor-β induced protein regulates pulmonary fibrosis via the G-protein signaling modulator 2/Snail axis. Peptides. 2022; 155: 170842. PubMed Abstract | Publisher Full Text\n\nOhno S, et al.: RGD-CAP (βig-h3) enhances the spreading of chondrocytes and fibroblasts via integrin α1β1. Biochim. Biophys. Acta (BBA) - Mol. Cell Res. 1999; 1451: 196–205. PubMed Abstract | Publisher Full Text\n\nKim J-E, et al.: Identification of Motifs for Cell Adhesion within the Repeated Domains of Transforming Growth Factor-β-induced Gene,βig-h3. J. Biol. Chem. 2000; 275: 30907–30915. PubMed Abstract | Publisher Full Text\n\nOh J-E, Kook J-K, Min B-M: βig-h3 Induces Keratinocyte Differentiation via Modulation of Involucrin and Transglutaminase Expression through the Integrin α3β1 and the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. J. Biol. Chem. 2005; 280: 21629–21637. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "262986",
"date": "07 May 2024",
"name": "Mateusz S. Wietecha",
"expertise": [
"Reviewer Expertise wound healing",
"fibroblasts",
"bioinformatics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this review article, the authors describe the functions of fibroblasts in the context of ECM remodeling and their interaction with macrophages, and make the claim that CTHRC1 and TGFBI are important modulators of this axis. Overall, the manuscript is well-written. However, the manuscript is uneven in how it presents information. As I outline below, some sections of the manuscript are overly superficial in their discussion of important concepts and rely on citing review articles rather than primary research papers. Meanwhile, some of the other sections of the manuscript simply list findings from primary research studies without providing a proper context for the reader to understand the findings. The two main themes of fibroblast-macrophage interactions and CTHRC1/TGFBI functions read like two separate narratives, and the connection between the two needs to made much more clear by the authors.\nThe following are a few suggestions to improve the manuscript: 1. The title should be changed to reflect the rather narrow focus on either fibroblast-macrophage interactions and/or the roles of CTHRC1 and TGFBI. 2. In general, the manuscript cites too many other reviews, especially when referring to specific facts/findings that should really be citing the original research papers that originated these findings. 3. Intro, paragraphs 2-4, and section on \"fibroblast heterogeneity dictates ECM deposition\": the discussion about fibroblasts' heterogeneity and their myriad functions during wound repair and fibrosis is overly simplistic, as is the depiction in Figure 2. In addition to the discussed ref. 34, there are several other recent primary research papers that should be cited and discussed here that directly address fibroblast heterogeneity and its effects on ECM composition during wound repair; see for example references Guerrero-Juarez CF et.al., 2019 (Ref 1), Gay Det.al., 2020 (Ref 2), Foster DSet.al.,2021 (Ref 3), Wietecha MS et.al., 2023 (Ref 4), Phan QM et.al., 2021 (Ref 5), Hu KH et.al., 2023 (Ref 6) below. Many of these papers also mention fibroblast-macrophage interactions and list CTHRC1 and TGFBI as genes of interest, but this requires a deeper dive that may better set the stage for the more focused discussion about TGF-beta signaling, CTHRC1 and BIGH3. 4. The sections on CTHRC1 and BIGH3 are a list of facts about their function in fibroblasts in various model systems and have very little to do with macrophages or fibroblast-macrophage interactions dictating ECM composition in disease states. Besides a couple sentences stating that both CTHRC1 and BIGH3 may also be produced by macrophages, how does this fit within the larger narrative the authors have established thus far? Are macrophages even the primary producers of these cofactors in disease states, or are fibroblasts? Indeed, the \"proposed model for cofactor-mediated ECM deposition in fibroblasts\" (Fig 4) does not show macrophages as producers of CTHRC1/BIGH3. 5. The statement \"This gene is also a paralog of periostin (POSTN)\" lacks context and explanation.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": []
},
{
"id": "262987",
"date": "17 May 2024",
"name": "Valentina Pucino",
"expertise": [
"Reviewer Expertise Immunology",
"Immunometabolism",
"fibroblast biology",
"T cell biology",
"autoimmunity."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI find this review timely and well written. It summarizes the latest findings on fibroblast biology and fibroblast-derived molecules offering an insight on potential therapeutic options to target fibroblast-mediated diseases such as fibrosis where therapeutic treatments are lacking. This is a hot topic at the moment. See detailed report below.\n\nThis review from Altieri et al. recapitulates the most recent findings in the field of fibroblasts. In addition, the authors discuss how fibroblasts coordinate immune responses, especially macrophages’ functions, by modulating ECM, and outline the molecular mediators such as CTHRC1 and TGFB and pathways regulating these processes. This is a very well written and timely review. Minor points: Add and discuss the following references: Fibroblasts orchestrate ECM deposition in steady state and disease: I would add few more words on fibroblasts heterogeneity here. Some key references below: Gauthier V,et.al., 2023 [Ref 1], Korsunsky I, et.al.,2022 [Ref 2], Muhl L, et.al., 2020 [3] ECM form & function: it’s worth to mention and discuss the paper by Horsnell et al 2023 in addition to reference number 4. Fibroblast derived cytokines and chemokines decorate the ECM to influence fibroblast-macrophage interactions: please add and discuss the following references which focus on fibroblast/macrophage interactions. Ng MTH, et.al.,2024 [Ref 5],Zhou X, et.al.,2022 [Ref 6], Meizlish ML, et.al., 2024 [Ref 7] Recent evidence has demonstrated that metabolic intermediates can also fuel stromal cell responses and ECM deposition and can regulate cellular crosstalk. Kay EJ, et.al., 2022 [Ref 8], Schwörer S,et.al.,2021 [Ref 9], Pucino V, et.al., 2023 [Ref 10] Major point: The proposed model at the end of the article is not very clear and can be improved.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-119
|
https://f1000research.com/articles/13-1488/v1
|
05 Dec 24
|
{
"type": "Opinion Article",
"title": "Addressing common inferential mistakes when failing to reject the null-hypothesis",
"authors": [
"Amand Schmidt"
],
"abstract": "Failure to reject a null hypothesis may lead to erroneous conclusions regarding the absence of an association or inadequate statistical power. Because an estimate (and its variance) can never be exactly zero, traditional statistical tests cannot conclusively demonstrate the absence of an association. Instead, estimates of accuracy should be used to identify settings in which an association and its variability are sufficiently small to be clinically acceptable, directly providing information on safety and efficacy. Post-hoc power calculations should be avoided, as they offer no additional information beyond statistical tests and p-values. Furthermore, post-hoc power calculations can be misleading because of an inability to distinguish between results based on insufficient sample size and results that reflect clinically irrelevant differences. Most multiple testing procedures unrealistically assume that all positive results are false positives. However, in applied settings, results typically represent a mix of true and false positives. This implies that multiplicity corrections do not effectively differentiate between true and false positives. Instead, considering the distributions of p-values and the proportion of significant results can help to identify bodies of evidence unlikely to be driven by false-positive results. In conclusion, rather than attempting to categorize results as true or false, medical research should embrace established statistical methods that focus on estimation accuracy, replication, and consistency.",
"keywords": [
"Statistical inference",
"null-hypothesis",
"equivalence testing",
"statistical power",
"accuracy."
],
"content": "Background\n\nStatistical tests and p-values are used to estimate the compatibility of the available data with a specific null hypothesis. While statistical tests and p-values are strongly embraced by applied researchers, statistical science has raised important concerns about their interpretability, which may lead to incorrect statements about the presence, absence, or importance of an association.1 This has led some researchers to suggest the replacement of p-values with alternative metrics, such as the S-value (i.e., S for surprise).2,3 The current manuscript attempts to provide an accessible overview of the voiced concerns about statistical testing, particularly focusing on the appropriate interpretation of “non-significant” results when a p-value or statistical test does not provide sufficient reason to reject the posed null hypothesis. In line with previous guidance in this area, this manuscript suggests moving away from categorizing results as True or False, instead suggesting research focusses on obtaining sufficiently accurate results on potential benefits and harms.\n\nAs an illustrative example, we will consider results from the VOYAGER PAD4 trial, which randomized patients with peripheral artery disease (PAD) to twice-daily rivaroxaban (2.5 mg) or a placebo, evaluating differences in the incidence of ischemic cardiovascular disease. The reported hazard ratio (HR) for rivaroxaban was 0.85 (95%CI 0.76; 0.96), tested against a null hypothesis HR of 1.00 resulted in a p-value of 0.006. Here the p-value indicates the proportion of subsequent trials (using the same design, intervention, and types of patients) which would result in an HR of 0.85 or more extreme, assuming the true population HR is 1. By convention, a p-value smaller than 0.05 is considered “significant”, however more stringent or liberal choices may also be applied. Aside from whether the CI rejects an HR of 1, the size of the 95%CI provides an indication of the variability of the HR, which in this case supports a small (HR of 0.96) or larger (HR of 0.76) benefit. Irrespective of the effect magnitude, there is reason to question the null hypothesis HR of 1, where the data provides most support for an HR of 0.85.\n\nIn the aforementioned example, there is substantial evidence against the null hypothesis, and hence, inference is fairly straightforward and uncontested. Conversely, interpreting results of “non-significant” analysis, where the null hypothesis cannot be rejected, may leads to erroneous conclusions such as claiming a lack of “statistical significance” supports the null hypothesis. For example, based on an HR of 0.86 (95%CI 0.40;1.87; p-value=0.71), the VOYAGER-PAD authors concluded that for the subgroup of patients with endovascular PAD, there was “no increase in intracranial or fatal bleeding”.5 While it is clear that the null hypothesis of no difference cannot be rejected, with the CI including an HR of 1.87, it is also clear that there is little evidence to support the absence of a harmful effect. Instead of claiming an absence of a risk-increasing effect, the presented results suggest that additional research is needed before drawing conclusions on bleeding risks.\n\nIn the following, I will discuss three common mistakes when interpreting results from statistical tests that fail to reject the null hypothesis: 1) claiming that the null hypothesis is true, 2) claiming that the study was underpowered, and 3) using multiple testing corrections to support claims about true or false associations.\n\n\nWhy a non-significant result does not rule out a potentially meaningful association\n\nThere are two types of hypotheses: a strict null hypothesis, where a supposed population parameter μ (e.g., the mean, mean difference, or hazard ratio) takes on a single value (e.g., μ=0 ), and a composite null hypothesis, where μ follows a range of values (e.g., 0.9<μ<1.1 ).\n\nAs with the illustrative examples, most often a strict null hypothesis is (implicitly) evaluated. Given that a strict null hypothesis postulates that μ is equal to a single value, it can be readily demonstrated that a statistical test cannot support the strict null hypothesis. This understanding stems directly from the fact that for an arbitrary function ∫ its integral sum with limits a=b is zero (see Extended data for a formal proof ). More intuitively, to prove that μ is equal to any single value, one must obtain an estimate with zero bias and infinite precision. Essentially, this requires divine knowledge about the value of μ .\n\nWhile a strict null hypothesis cannot be supported by the data, no matter how much data is collected, there may often be a need to rule out certain effect(s). For example, the risk of bleeding when treating patients with rivaroxaban, or identifying interventions with limited efficacy. The solution is to simply use composite null hypotheses. Returning to the illustrative example, one might consider a risk-increasing effect of 1.25 or less as sufficiently modest to not offset the observed benefit on ischemic cardiovascular disease. In this case, the null hypothesis would be μ0≥1.25 , which would be rejected when both the estimated HR and the upper bound of the CI are smaller than 1.25. estimate 2 in Figure 1 reflects the VOYAGER PAD estimate of the rivaroxaban bleeding effect, and it is clear that the confidence interval includes HRs above 1.25; hence, the null hypothesis should not be rejected and there is no reason to conclude that rivaroxaban has a relatively small effect on bleeding risk. However, estimate 4 is HR 1.15 (95%CI 1.06; 1.24), which does exclude a HR larger than 1.25. Thus while showing an risk increasing effect, one can nevertheless conclude that the effect size is sufficiently small to suggest that rivaroxaban is relatively safe.\n\nN.b. Points represent hazard ratios (HR) with horizontal lines indicating 95% confidence intervals (CI). The orange vertical line indicates margins of equivalence at 0.80 and 1.25, with the vertical line at 1.00, indicating no difference. Estimates 1-2 are based on the VOYAGER PAD5 rivaroxaban results for ischemic cardiovascular disease and bleeding risk, respectively. Estimates 3-5 are purely hypothetical and included as illustrations.\n\nThis procedure is referred to as non-inferiority testing, where 1.25 is the bound of equivalence. Depending on what is deemed clinically non-inferior, such a bound can be substantially larger or smaller. For example, in the EBBINGHAUS trial of the PCSK9-inhibitor evolocumab the equivalence bound was set equal to 20% of the standard deviation of the cognitive function score measured in the placebo group.6 The key characteristic of non-inferiority testing for safety is that both the point estimate (here, the HR) and the upper bound of the CI should be smaller than the supposed bound of equivalence. Similarly, a non-inferiority test for effectiveness (e.g., compared with active interventions) would ensure that the point estimate and lower bound of the CI are larger than a bound of equivalence which is set towards a protective direction (e.g. an HR below 1). Given that one is not testing against a strict null hypothesis of no difference, whether confidence (or statistical test) refutes a neutral value is immaterial. The consideration of two bounds, one on each side of a neutral HR of 1, naturally leads to equivalence testing. For example, in Figure 1, both estimates 4 and 5 are deemed equivalent, despite both rejecting an HR of 1.0.\n\nIdeas on non-inferiority and equivalence can be further generalized by considering the entire range of CIs providing information on precision and the HRs supported by collected data2 ( Figure 2). For example, the rivaroxaban trial data support a wide range of bleeding risk HRs, and an HR of 1.25 would only be excluded using a 66%CI ( Figure 2, left panel). This can be contrasted by the small range of HRs supported by the rivaroxaban trial data for a protective effect on ischemic cardiovascular disease, indicating that the trial data are highly supportive of a protective effect ( Figure 2, right panel).\n\nVertical lines indicate a hazard ratio (HR) of 1.00, and a possible margin of equivalence for an HR of 1.25. The shaded area indicates the HRs supported for a given coverage probability, indicated on the y-axis.\n\n\nWhy post-hoc power provides the same information as a p-value or null hypothesis test\n\nFailure to reject a null hypothesis naturally raises concerns about whether the study was sufficiently powered to detect a difference, often tempting researchers to conduct “post-hoc” or “observed” power calculations utilizing the observed point estimates (e.g. HRs) and variance estimates. Briefly, power reflects the probability of rejecting the null hypothesis if it is false. This is the direct opposite of statistical tests and related quantities, such as p-values, which reflect the rejection probability assuming the null hypothesis is true.\n\nAs such, p-values and observed power are equivalent, and no additional information is obtained by considering both ( Figure 3). To see this, we observe a p-value of 0.05, which is short of the conventional level of significance indicated by an alpha (i.e., the type 1 error rate) of 0.05. In this case, observed power can be obtained by calculating the propbability of rejecting the null hypothesis assuming the point estimates and it standard error are the true population values (which implies that the null hypothesis is false), which in this case would be exactly 50% ( Figure 3). As such, while p-values evaluate the difference between the estimated values and the null hypothesis assuming the former is true, power evaluates the same difference assuming the null hypothesis is false. Hence, when p-values have been calculated, calculating observed power offers no additional information about the absence or presence of a difference.\n\nAlpha refers to the type 1 error rate of a test. The dashed lines on the x-axis indicate the locations where the p-value is exactly equal to the alpha. The dashed lines on the y-axis indicate an observed power of 50%.\n\nMore concerning is that post-hoc power calculations may lead to erroneous conclusions regarding the lack of statistical power. For example, the following two HR estimates both have a p-value of 0.71 and a power of 11%: HR 0.86 (95% CI 0.39; 1.91), HR 1.00 (95%CI 0.99; 1.01). Looking at the post-hoc power, one might conclude that both analyses were underpowered; however, the HR of 0.86 is non-significant due to considerable variability, whereas the latter HR of 1.00 simply reflects a clinically irrelevant association. Hence, a more relevant alternative to post-hoc power calculations is to evaluate the extent to which the CI includes clinically relevant effect estimates, which is in line with the afore mentioned equivalence/non-inferiority approach.\n\n\nWhy multiple testing correction does not differentiate between true and false results\n\nConsiderations of power and type 1 error rate are extremely relevant when designing a study, ensuring that a sufficiently accurate effect estimate may be realistically obtained given the available resources. Given that power and type 1 error make extreme assumptions where either all results are true or false positives, these concepts are less relevant after the data have been collected. It is important to realize that the type 1 error rate itself does not reflect the proportion of false positive results, but merely reflects the expected proportion of false positive results should all null hypotheses be true.\n\nWhen considering the results of two or more null hypothesis tests, in an attempt to decrease the number of false positive results, there is an expectation to perform multiple testing corrections. For example, the Bonferroni method is a popular multiplicity correction evaluating results against an alpha (e.g., 0.05) divided by the number of conducted tests. It is well known that post-hoc multiple testing correction (e.g., corrections not accounted for during the design stage by increasing the collected sample size) will decrease power ( Figure 3). An often overlooked point is that, depending on the unknown balance between false positives and true positives in a set of test results, applying multiplicity correction can sometimes increase the false positive rate instead of reducing it. For example, Figure 4A presents a naïve expectation of multiple testing corrections, where the false positive rate decreases from 1/3 to 0. However, there is no reason why the scenario depicted in Figure 4B may not occur; here, the false-positive rate increases from 1/3 to 1.\n\nIn each panel, four tests are true positives (orangered) and six are false positives (black). Horizontal lines are drawn at 0.05 and 0.005, the latter reflecting a Bonferroni correction for the 10 applied null hypothesis tests.\n\nAs shown in Figure 5, in which the distribution of p-values is generated in the absence and presence of an association, small p-values may occur in both settings. As such, while a small p-value (or equivalently, a extreme test statistic) is unlikely to occur when there is no association, observing a single small p-value is insufficient to differentiate between true and false positive results. Concepts such as indirect or direct replication and internal consistency are more relevant to differentiate between true and false positives. For example, in the case of rivaroxaban, associations with multiple types of ischemic cardiovascular events (e.g., myocardial infarction, ischemic stroke, and acute limb ischemia) will be more convincing than an association with any one outcome.\n\nN.b. The p-values were based on random draws from a normal distribution with a standard deviation of 1 and mean of either 0 or 2.\n\nWhile individual p-values and null hypothesis tests cannot differentiate between false and true positive results, a set of p-values ( Figure 5) can be compared against a uniform distribution to determine the likelihood that the entire set is driven by false positive results. Similarly, one can determine the proportion of p-values that are smaller than a predefined alpha; for example, in Figure 5, the proportion of p-values smaller than 0.05 is of course 0.05 for the top panel and 0.49 for the lower panel. Returning to our illustrative example, despite showing a potentially protective association with myocardial infarction, ischemic stroke, major amputation, and venous thromboembolism, the null hypothesis could only be rejected for the association between rivaroxaban and acute limb ischemia: HR 0.67 (95% 0.55; 0.82).4 Nevertheless, comparing the set of p-values for all the aforementioned outcomes against a uniform distribution resulted in a p-value of 0.02, suggesting that the protective effect of rivaroxaban is shared across multiple cardiovascular outcomes.\n\n\nDiscussion\n\nIn the current manuscript, I have explained why statistical tests cannot be used to support the strict null hypothesis. Instead, concerns regarding the safety or lack of efficacy should be evaluated using equivalence testing. This can be readily implemented in any study by combining confidence intervals with bounds of clinical insignificance. Such an approach provides direct information on whether a non-significant test is due to an association and its variability being sufficiently small or simply reflects a lack of accuracy. This approach also provides information whether it would be useful to repeat the analysis with a larger sample size, eliminating the need for post-hoc power calculations, which can lead to misleading conclusions. Furthermore, contrary to expectation and depending on the unknown proportion of true positive results, multiple testing corrections may increase the false positive rate. Finally, because power and type 1 error rate make extreme assumptions about whether all results are true or false positives, these concepts have limited relevance after the data have been collected and analyzed.\n\nThe current manuscript provides guidance on how standard null hypothesis testing can be used to provide clinically meaningful insights, and attempts to move beyond the current erroneous modus vivendi, categorizing associations as true and false. Contrary to recent calls to completely abandon significance testing,2 this contribution calls for a more considerate and bespoke application of the currently available and ubiquitously accepted methods. Specifically, researchers should routinely indicate the bounds between which an effect is sufficiently small to be considered clinically irrelevant. Related to this, the idea that any intervention should (or even can) be without harmful side effects needs to be dismissed and replaced with a notion of benefit versus harm, where clinically supported bounds off irrelevance can help to directly inform. Second, while notions of power and type 1 errors are essential at the study design phase because these deal in hypothetical scenarios where all results are either true or false, such metrics have limited relevance when interpreting results. Power and type 1 errors can be framed in terms of probabilities because the analysis has not yet been conducted. Once the experiment has been completed, these hypothetical probabilities are immaterial, and one is simply confronted with an unknown proportion of true-positive results. At this stage, concepts of power and type 1 error must be replaced by indicators of precision, such as confidence intervals. Instead of using confidence intervals as a proxy for null hypothesis testing (i.e., whether the null hypothesis value is excluded), inference should focus on determining to what extent there is sufficient precision to exclude meaningful differences. Finally, depending on the area of research overlooked, true positive results may be more harmful than false positive results. For example, protein drug targets identified in early drug development are often subjected to a substantial number of follow-up analyses, which filter out false-positive results. Such follow-up studies, however, rarely expand the number of candidates, hence suggesting a more inclusive approach might be more considerate. Of course, in settings more proximal to clinical implementation and less discovery oriented, such as phase 3 clinical trials, stringent multiple testing correction is clearly called for. Notwithstanding, it is important to realize that not every study needs to be designed as a clinical trial.\n\nIn conclusion, failure to reject a strict null hypothesis does not support the absence of a clinically meaningful association. Instead, researchers should routinely apply composite null hypothesis tests evaluated against meaningful bounds of insignificance. Genuine consideration of estimation accuracy, as provided through confidence intervals, precludes the need for questionable post-hoc power calculations. Finally, because power and type 1 errors unrealistically assume that all results are true or false, these concepts have limited value once data collection and analysis have been completed.\n\n\nAuthor contributions\n\nAFS designed the illustrations and wrote the manuscript.\n\n\nEthics and consent\n\nEthics and consent were not required.",
"appendix": "Data availability\n\nNo data associated with this article.\n\nAddressing common inferential mistakes when failing to reject the null hypothesis https://doi.org/10.5522/04/27854043.7\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nWasserstein RL, Lazar NA: The ASA Statement on p-Values: Context, Process, and Purpose. Am. Stat. 2016; 70: 129–133. Publisher Full Text\n\nRafi Z, Greenland S: Semantic and cognitive tools to aid statistical science: replace confidence and significance by compatibility and surprise. BMC Med. Res. Methodol. 2020; 20: 244. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCole SR, Edwards JK, Greenland S: Surprise!. Am. J. Epidemiol. 2021; 190: 191–193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBonaca MP, et al.: Rivaroxaban in Peripheral Artery Disease after Revascularization. N. Engl. J. Med. 2020; 382: 1994–2004. Publisher Full Text\n\nRymer J, et al.: Rivaroxaban Plus Aspirin Versus Aspirin Alone After Endovascular Revascularization for Symptomatic PAD: Insights From VOYAGER PAD. Circulation. 2023; 148: 1919–1928. PubMed Abstract | Publisher Full Text\n\nCalabro P, Gragnano F, Pirro M: Cognitive function in a randomized trial of evolocumab. N. Engl. J. Med. 2017; 377: 1996–1997. PubMed Abstract | Publisher Full Text\n\nAddressing common inferential mistakes when failing to reject the null hypothesis. DOI: 10.5522/04/27854043"
}
|
[
{
"id": "350489",
"date": "02 Jan 2025",
"name": "Ying Cui",
"expertise": [
"Reviewer Expertise Hypothesis testing",
"Biostatistics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe author have made very interesting points on common mistakes when interpreting results from statistical tests that fail to reject the null hypothesis. There are some minor comments as listed below:\n1. In Page 5, it was mentioned that \"Hence, a more relevant alternative to post-hoc power calculations is to evaluate the extent to which the CI includes clinically relevant effect estimates, which is in line with the aforementioned equivalence/non-inferiority approach.\". It can be helpful if the author could provide a specific example (e.g. further discussion with the two HR estimates using equivalence/non-inferiority approach) to further illustrate this.\n2. In the last line of Page 5, \"naïve\" should be \"naive\".\n3. In the last lines of Page 7, it was recommended that \"researchers should routinely apply composite null hypothesis tests evaluated against meaningful bounds of insignificance\". It would be helpful if the author could provide more discussion with suggestions on how to identify the \"bounds of insignificance\".\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "350494",
"date": "07 Jan 2025",
"name": "J. Alexander Heimel",
"expertise": [
"Reviewer Expertise Neuroscience"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript, “Addressing common inferential mistakes when failing to reject the null-hypothesis” contains two main messages. First, the author argues that post-hoc power calculations should be avoided, as “they offer no additional information beyond statistical tests and p-values” and they “can be misleading because of an inability to distinguish between results based on insufficient sample size and results that reflect clinically irrelevant differences”. Second, for interpreting the results of multiple comparison, the authors recommends to consider “the distribution of p-values and the proportion of significant results to identify bodies” rather than standard multiple testing procedures, because they “unrealistically assume that all positive results are false positive”. The paper is an interesting read, but I have a few remarks.\nI have two comments on the first point.\n“p-values and observed power are equivalent, and no additional information is obtained by considering both ( Figure 3).” No proof is given of this statement and it is not completely trivial. Can a (hint of a) proof be given or a reference with a proof cited? I believe the relationship shown and figure 3 between p and power depends on the number of samples, but this is not shown in the text or figure. Can you comment on this? The dependence on the sample number could give some added value for making this post-hoc power calculation, and p-values and observed power are thus not completely equivalent.\nAre there examples that people do this particular post-hoc power calculation using the measured effect and the measured standard deviation? What I have encountered, is post-hoc power calculations based on the measured standard deviation of the sample, and for an assumed effect size (rather than the measured effect). If there are publications doing the post-hoc power analysis in the way suggested by this publication, then please give some example references. Otherwise, the reader is left to wonder if this part of the manuscript is arguing against hypothetical reasoning that people do not actually use.\nThe second point of the paper is that “While individual p-values and null hypothesis tests cannot differentiate between false and true positive results, a set of p-values (Figure 5) can be compared against a uniform distribution to determine the likelihood that the entire set is driven by false positive results.” This can indeed be helpful. However, if assumptions like independence between tests or normality of the measurements for some tests fail, then this meta-analysis on the p-value may give a false positive outcome. Without a good understanding of the underlying data and statistics, I would use this test only to suggest that results are possibly false positives if the distribution of p-values is not distinguishable from a uniform distribution, rather than concluding that there must be some true positive effect if the distribution of p-values is not uniform, as is done by the author for the specific example for the effect of rivaroxaban.\nThese are my main comments. I also have a number of smaller remarks.\nThe manuscript also discusses whether null hypothesis testing can prove whether difference in means between two (infinite) populations is truly zero, but I fail to see the connection of this more philosophical point on the interpretation of hypothesis testing to the main messages. I think that the manuscript would be stronger if it is left out.\nThe meaning of the sentence “Given that power and type 1 error make extreme assumptions where either all results are true or false positives, these concepts are less relevant after the data have been collected. ” is not at all clear to me. Perhaps rephrase to clarify.\n“applying multiplicity correction can sometimes increase the false positive rate instead of reducing it.” In this sentence, and the ensuing section the term “false positive rate” is used differently from what is the common use in the statistical literature. In the literature, “false positive rate” is the expectation of a false positive result when repeating the procedure. The meaning that is taken in this manuscript is that of the fraction of the significant results of a given set of experiments that is a false positive. It is not clear that the interpretation chosen here, and which is shown by example to lead to a false expectation, actually often occurs in the scientific literature. Can some example references be provided?\nFig. 5: The number of samples used for producing the figure is missing.\n“comparing the set of p-values for all the aforementioned outcomes against a uniform distribution resulted in a p-value of 0.02,” Which test is used for the comparison.\n“researchers should routinely indicate the bounds between which an effect is sufficiently small to be considered clinically irrelevant” This is a valuable recommendation. Before the start of a study it is necessary to choose an expected effect size for determining the power of a study or the number of samples. If the expected effect size, is below the bound, then either the study should not be started (if one is looking to prove a positive effect) or the bound should be taken as the effect size for the power calculation.\n“Second, while notions of power and type 1 errors are essential at the study design phase because these deal in hypothetical scenarios where all results are either true or false, such metrics have limited relevance when interpreting results.” I do not fully agree. For a power analysis at the design phase, typically both an effect size and the variance need to be estimated. In my opinion, a post-hoc power analysis could be relevant for interpreting a negative result, to take into account the observed variance. If the variance is a lot larger than a priori expected, then the study could have been underpowered. Perhaps adjust the text, or explain why I am wrong.\nI do not understand “Finally, depending on the area of research overlooked, true positive results may be more harmful than false positive results”. Is meant that setting too stringent boundaries for significance can be harmful? Consider rephrasing to make its meaning clear.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1488
|
https://f1000research.com/articles/13-102/v1
|
16 Feb 24
|
{
"type": "Research Article",
"title": "Impact of contingent rewards and punishments on employee performance: the interplay of employee engagement",
"authors": [
"Debika Layek",
"Navin Kumar Koodamara",
"Debika Layek"
],
"abstract": "Background This paper investigated the connection between transactional leadership styles, contingent rewards, punishments, and employee performance while emphasizing employee engagement’s mediating role. Existing research has predominantly focused on isolated associations between contingent rewards, punishment, and employee performance, leaving gaps in the empirical exploration of these mediating mechanisms. To address this research gap, our study has introduced a conceptual framework to understand the multifaceted connection between contingent rewards, punishment, and their effects on employee performance, with a specific emphasis on the mediating function of employee engagement.\n\nMethods We involved 273 full-time non-clinical healthcare professionals employed in NABH-accredited hospitals in Jharkhand, India. A structured survey instrument was employed for data collection from the specific survey participants, with the investigation of the research hypotheses conducted through the application of partial least squares-structural equation modeling (PLS-SEM).\n\nResults Preliminary findings suggested that contingent rewards and punishment do not directly influence employee performance. Instead, our study highlighted the critical mediating role of employee engagement, particularly its dimensions of Vigor, absorption, and dedication.\n\nConclusions This research has underscored rewards and punishments as essential tools for influencing employee behaviour, motivation, and performance. Employee engagement, as a multifaceted construct, not only benefits individual employees but also significantly impacts overall organizational performance and success.",
"keywords": [
"Transactional leadership",
"Contingent rewards",
"Contingent punishments",
"Employee Engagement",
"Employee Performance."
],
"content": "Introduction\n\nThe rapid evolution of the economic landscape and the dynamic shifts within the business environment have engendered heightened levels of market competition. Considering these circumstances, the cultivation of apt leadership attitudes for navigating an uncertain environment has emerged as a formidable challenge. Consequently, there is an acute necessity for leaders who can not only meet anticipations but also confer a competitive advantage to enhance the performance of employees (Frangieh & Rusu, 2021; Xie, et al., 2018). Over the past few decades, the realm of leadership has commanded considerable scholarly and practical attention across diverse domains of organizational management. Amongst the numerous leadership paradigms, transformational and transactional leadership have surfaced as the most prominent and widely examined styles within the purview of organizational management (Baafi, Ansong, Dogbey, & Owusu, 2021; Tyssen, Wald, & Spieth, 2014).\n\nWhile existing research generally confirms the heightened efficacy of transformational leadership, the present study adopts a more focused approach, centering its inquiry upon transactional leadership. Transactional leaders, in their operational modality, concentrate on the delineation of unambiguous objectives through the interpretation of the reciprocal connection between conferred rewards/punishments and anticipated performance outcomes. Moreover, they consistently engage in the process of furnishing feedback to sustain the concentration of employees on the attainment of their assigned tasks. The influence of transactional leadership on employee performance finds its theoretical underpinning in the tenets of Social Exchange Theory (Young, Glerum, McCord, & Joseph, 2021). This framework posits that transactional leaders exhibit a profound understanding of the inherent needs and desires of their subordinates, and they proactively articulate how these requisites can be viably fulfilled as proportionate rewards for the enhancement of employee performance. Consequently, leaders operating within this paradigm must judiciously administer a system of rewards and punishments, thereby competently resolving the intricacies associated with the execution of tasks (Podsakoff, Bommer, Podsakoff, & MacKenzie, 2006).\n\nDrawing from existing research findings, it becomes apparent that while there exists substantiating evidence for the constructive influence of transactional leadership on employee performance, there are also divergent studies that present conflicting perspectives. These contrasting investigations state that transactional leadership can exert a noteworthy adverse impact on employee performance (Jia, Chen, Mei, & Wu, 2018) or, alternatively, posit that transactional leadership may not have any apparent effect on employee performance (Baig et al., 2021; Jacobsen, Andersen, Bøllingtoft, & Eriksen, 2022).\n\nIn this context, the pivotal roles played by engaged employees are of notable significance. When employees establish a meaningful link with their organization, they tend to exhibit an increased inclination toward enhancing their effectiveness (Demerouti, Cropanzano, Bakker, & Leiter, 2010). Presently, a substantial body of research literature is progressively corroborating the affirmative influence of Employee Engagement (EE) on Employee Performance (EP) (Christian, Garza, & Slaughter, 2011; Kanten & Sadullah, 2012). Engaged employees consistently demonstrate a heightened commitment to optimizing their performance and expanding their responsibilities (Anitha, 2014). This underscores the feasibility of utilizing employee engagement as a predictive factor for employee performance. Notwithstanding the considerable attention accorded to engagement by both practitioners and researchers as a pivotal factor in the realm of work-related dynamics, it is imperative to acknowledge that the definitions and measurement methodologies pertaining to engaged employees, particularly within the context of healthcare services, remain inadequately comprehended. Hence, this research study aims to undertake an exhaustive analysis to elucidate the impact of a transactional leadership style, characterized by contingent rewards and punishments, on employee performance. Furthermore, this study endeavors to illuminate the mediating role of engagement in the context of employee performance.\n\nThis study is important to assess the influence of employee engagement on transactional leadership style and performance of employees. This research study represents a novel undertaking, as it constitutes the first effort to assess the variables pertaining to interpersonal relationships within the specific context of India, with a primary emphasis on nonclinical healthcare professionals.\n\n\nLiterature review\n\nThe concept of transactional leadership, as initially formulated by (Burns & MacGregor, 1978) centers on a dynamic where subordinates willingly engage in a reciprocal relationship with their leaders, anticipating various forms of rewards, whether monetary or non-monetary (Burns & MacGregor, 1978). This agreed interconnection does not elicit a shift in the roles of the subordinates; rather, it hinges on the transactional leader’s reliance on conventional rewards and punishments to ensure compliance with organizational directives and the attainment of its objectives (Pathak, Madan, & Srivastava, 2023). This notion, as posited by Bass (1985) posits the existence of an exchange-based association between leaders and their followers. The exchange theory underpinning transactional leadership is pragmatically oriented, emphasizing mutual goal achievement for both parties involved (Abdelwahed, Soomro, & Shah, 2022). Bass (1985) contends that transactional leaders motivate their followers by establishing clear objectives, outlining direct pathways to goal attainment, providing lucid performance evaluations and feedback, and guaranteeing rewards upon target realization. In this role, these leaders assume the position of evaluators, elucidating the responsibilities of their followers in pursuit of predetermined objectives and administering rewards and punishments based on performance outcomes. Thus, the exchange of interests emerges as a pivotal facet that mutually benefits both leaders and followers (Politis, 2002).\n\nIn Blau (1968) the Social Exchange Theory (SET) is explained as a conceptual framework elucidating the dynamics of reciprocity among individuals within various contextual settings. This theoretical construct posits a comprehensive interpretation of the impact of employees’ levels of engagement on their workplace performance (Saks, 2006). The level of engagement is intricately developed through the lens of exchange theory. Kahn (1990) is credited with pioneering the terminology of ‘employee engagement,’ characterizing it as the extent to which employees manifest tangible involvement, cognitive capability, and emotional attachment to their job responsibilities. Engaged employees are filled with a sense of skill in strategic planning, and decision-making processes. Such motivated individuals exhibit an inclination to channel their utmost efforts and leverage their exceptional abilities to transcend the minimal requisites for organizational advancement (Breevaart et al., 2014; Kalia & Verma, 2017). In addition to this conceptualization, Schaufeli et al. (2002) define engagement as a positive and enriching cognitive state in the occupational context, characterized by three fundamental dimensions. Vigor, the first dimension, manifests through heightened levels of physical and mental energy, coupled with a robust capacity for resilience while engaged in work-related tasks. Dedication, the second dimension, encompasses an emotional landscape characterized by a profound sense of significance, enthusiasm, inspiration, pride, and a constant thirst for challenges associated with one’s professional endeavors. The third dimension, absorption, reflects a state of complete immersion and contented absorption in the execution of one’s occupational responsibilities, signifying a holistic and harmonious alignment between the individual and their work environment (Schaufeli, Salanova, Roma, & Bakker, 2002).\n\nPerformance is a complex construct encompassing various facets, such as task performance and the contextual roles assumed by employees (Chaudhary, 2020). It signifies the actions and behaviors exhibited by employees concerning their job-related responsibilities, as well as non-job-related aspects pertinent to the organizational objectives. Furthermore, performance is characterized by the capacity of employees to adapt their conduct in order to meet the requirements of their work (Park, Lim, Kim, & Kang, 2020). This adaptability contributes to the generation and implementation of innovative and valuable ideas that align with the formal requisites of the job and the proficient fulfillment of assigned duties (Abdurachman et al., 2023).\n\nLeaders who employ a contingent reward system demonstrate a tendency for establishing explicit objectives and effectively communicating the anticipated outcomes to their followers, thereby eliciting motivation among their subordinates (Bass & Avolio, 1994). This aligns with the findings of a comprehensive meta-analysis conducted by Judge and Piccolo (2004), which validates the notion that contingent rewards play a pivotal role in enhancing the motivation levels of individuals engaged in the workforce. In contrast, the concept of contingent punishment revolves around an employee’s perception of a leader who meticulously delineates behavioral and performance standards, and subsequently administers various forms of negative feedback, such as criticism or expressions of displeasure, when the employee fails to follow to these established standards (MacKenzie, Podsakoff, & Rich, Transformational and Transactional Leadership and Salesperson Performance, 2001). This approach underscores the significance of apparent negative reinforcement cues exhibited by leaders, wherein employees face warnings and social disapproval for straying from established regulations and expectations (Podsakoff, Bommer, Podsakoff, & MacKenzie, 2006). This suggests the extent of an employee’s commitment to their work hinges significantly on the prospect of receiving either rewards or punishments. Consequently, organizations may encounter challenges in fostering change since their leaders are predominantly preoccupied with procedural aspects, tend to focus on identifying faults for punitive measures, and prioritize acknowledging achievements for reward purposes rather than actively cultivating engaged employees (Thanh & Quang, 2022).\n\nConsiderable attention has been directed towards examining the connection between employee engagement and the evaluation of employee performance. The engagement of employees within the organizational framework yields advantages not only for the employer but also for the employees themselves (Demerouti, Cropanzano, Bakker, & Leiter, 2010). An establishment of a meaningful connection between employees and the organization invariably promotes a desire for heightened effectiveness among the employees. In contrast, engaged employees consistently outperform their non-engaged counterparts (Demerouti, Cropanzano, Bakker, & Leiter, 2010). This underscores the intrinsic connection between engagement and employee performance. Studies validate that the initial consequence of employee engagement manifests as augmented employee performance, thereby culminating in amplified organizational performance (Robbins, Judge, & Vohra, 2019). Engagement offers employees the opportunity to invest themselves in their work and fosters a sense of self-efficacy. Research exploring the ramifications of employee engagement suggests that it can yield positive outcomes in terms of employee well-being and cultivate favourable attitudes towards work and the organization (Nguyen & Nguyen, 2022). Employee engagement, in essence, denotes the extent to which individuals exhibit identification with their work, actively participate therein, and ascribe importance to their performance as a reflection of their self-worth (Yandi & Havidz, 2022). A comprehensive synthesis of these findings leads to the inference that work involvement comprises employee participation, marked by a profound dedication to their tasks, transcending personal interests, and emphasizing the overarching importance of the organization. When employees demonstrate a heightened degree of engagement with their employer, their focus extends beyond mere work-related goals, encompassing positive perceptions and emotions, thereby motivating them to exert greater effort in their professional endeavours (Anitha, 2014). Consequently, a detailed examination of the factors underpinning engagement becomes imperative, as they serve as crucial determinants for predicting employee performance.\n\nTransactional leadership can be conceptualized as a form of consensual arrangement between leaders and their subordinates aimed at attaining organizational objectives (Northouse, 2021). In this leadership paradigm, leaders incentivize employees through the provision of rewards contingent upon the successful execution of tasks that contribute to the maintenance or enhancement of overall employee performance. Transactional leadership model revolves around the fundamental notion of exchanges wherein rewards, both psychological and material, are offered by leaders to their followers in return for their labour (Donkor & Zhou, 2020). Furthermore, the efficacy of this leadership style is fortified through the implicit or explicit threat of punishments. This theoretical framework operates under the assumption that effective leadership necessitates the cultivation of desired follower behaviours while concurrently mitigating undesirable ones, achieved through the withholding of rewards and the imposition of tangible or psychological penalties (Alrowwad, Abualoush, & Masa’deh, 2020). In practice, it is typically immediate supervisors who are endowed with the authority to delineate performance objectives for employees, deliver constructive feedback, extend support in exchange for employee efforts, appraise individual performance, and extend recommendations for rewards based on performance evaluations (Han, Bartol, & Kim, 2015). Leaders who exhibit a propensity for contingent punishment are positively associated with enhanced employee performance (Podsakoff, Podsakoff, & Kuskova, 2010). They posit that negative feedback, when merited, can exert more constructive effects on employee performance than unwarranted positive feedback. The accountability imposed by leaders upon employees for subpar performance is typically met with greater employee satisfaction concerning their superiors, colleagues, and prospects for career progression (Podsakoff, Podsakoff, & Kuskova, 2010).\n\nHypothesis:\n\nH1: Contingent rewards (CR) have a positive effect on employee performance (EP) of non-clinical healthcare professionals in the healthcare sector.\n\nH2: Employee Engagement (vigor, absorption, and dedication) positively mediates the relationship between contingent rewards (CR) and employee performance (EP) of non-clinical healthcare professionals in the healthcare sector.\n\nH2a: CR ➔ Vigor ➔ EP\n\nH2b: CR ➔ Absorption ➔ EP\n\nH2c: CR ➔ Dedication ➔ EP\n\nH3: Contingent punishments (CP) have a positive effect on employee performance (EP) of non-clinical healthcare professionals in the healthcare sector.\n\nH4: Employee Engagement (vigor, absorption, and dedication) positively mediates the relationship between contingent punishments (CP) and employee performance (EP) of non-clinical healthcare professionals in the healthcare sector.\n\nH4a: CP ➔ Vigor ➔ EP\n\nH4b: CP ➔ Absorption ➔ EP\n\nH4c: CP ➔ Dedication ➔ EP\n\n\nMethods\n\nThis research has been carried out in strict adherence to established ethical guidelines, having received the requisite ethical clearance from the Institutional Ethics Committee at Kasturba Medical College and Kasturba Hospital, Manipal, Karnataka, India as documented under Reference Number IEC1:171/2022. In conducting this non-experimental, survey-based research, we obtained written informed consent from all participants, which was included within the questionnaire document. Participants were granted the option to discontinue their participation in the survey at any juncture, with the assurance that their personal information would be treated with utmost confidentiality.\n\nTo examine the hypotheses, we undertook an empirical study with non-clinical healthcare professionals. The population was composed of all the National Accreditation Board for Hospitals & Healthcare Providers (NABH) -accredited private hospitals located in Jharkhand, India. The data collection process involved obtaining online informed consent from the participants, and an online web-based Microsoft form was prepared and circulated through email. The purpose of the research was explained to the respondents. The present study employed a purposive sampling methodology to gather responses from employees within distinct departments, such as operations, general administration, patient care services, medical insurance, and quality assurance. This approach was chosen due to constraints in the number of available respondents. The primary emphasis of participant selection centered on nonclinical healthcare professionals who are not directly engaged in patient treatment and care services. This targeted sampling strategy was implemented to ensure the acquisition of the most relevant and insightful information for the research.\n\nThe final sample consisted of 273 employees. The questionnaire consisted of information on demographic factors, details on the respondent’s gender, age, current organizational designation, total working experience (Layek & Koodamara, 2023b). The questionnaire consisted of information on demographic factors, details on the respondent’s gender, age, current organizational designation, and total working experience. Data collection took place over a one-month period, commencing on February 10, 2023, and concluding on March 12, 2023. Participants were drawn from five distinct functional departments—operations, general administration, patient care services, medical insurance, and quality assurance. Exclusion criteria encompassed individuals encountering difficulties comprehending the English language. The dataset (Layek & Koodamara, 2023a) underwent analysis utilizing Partial Least Squares-Structural Equation Modeling (PLS-SEM), and the entire dataset exhibited an absence of missing values which enhances its integrity, contributing to a thorough and precise portrayal of inter-variable relationships and, consequently, facilitates the explanation of findings derived from the PLS analysis.\n\nWe used well-established scales to measure the study variables. Contingent rewards and punishments of transactional leadership style were measured using eight items proposed by Podsakoff et al. (1990) and MacKenzie, Podsakoff, and Rich (2001). Employee engagement was measured using the 17 items scale proposed by Schaufeli et al. (2002). Employee performance was assessed with 18 items scale proposed by Villagrasaa et al. (2019). The respondents assessed all items on a five-point Likert scale (5 = Strongly agree; 4 = Agree, 3 = Neutral, 2 = Disagree, 1 = Strongly disagree) to enhance the functionality and clarity of the questionnaire.\n\nCommon method variance bias was effectively assessed Since the data was collected from the respondents in a one-time survey. We used procedural and statistical methods to control for potential common method bias (Podsakoff, MacKenzie, Podsakoff, & Lee, 2003). Regarding the procedural techniques employed, we took measures to guarantee the confidentiality of the information furnished by the respondents. Furthermore, the study constructs were arranged randomly into the questionnaire to prevent respondents from inferring cause-effect relationships among the constructs. Regarding the statistical procedures, we implemented a full collinearity test based on variance inflation factors (VIFs), following (Kock & Lynn, 2012). It specifies when a VIF value is greater than 3.3, it indicates collinearity suggesting the existence of common method bias. Our estimations demonstrated that the VIF values fall below the designated threshold, indicating that the issue of common method bias is not of significant concern in this study.\n\n\nResults\n\nThe engagement of nonclinical healthcare professionals is crucial for several reasons, and it plays a significant role in enhancing their overall performance. When employees are motivated and committed, they are more likely to provide excellent service. The current study reveals the natural inclination of nonclinical healthcare professionals towards roles aligning with their personal preferences, suggesting a propensity for engagement beyond external rewards. These findings emphasize the organizational duty to provide work environments infused with enthusiasm, creating a setting conducive to dynamic and engaged professional experiences.\n\nThe research model was tested using partial least squares (PLS). Smart PLS 4 was used (Figure 1).\n\nTable 1 reports the results of the measurement model. To evaluate the adequacy of the measures of the construct model, we assessed the indicator’s individual reliability by examining the loadings of the measures on their corresponding latent constructs. All the construct composite reliability ratios exceeded 0.7, which confirms an adequate correlation between indicators and their respective variables. Convergent validity was assessed which is defined byHenseler, Ringle, & Sinkovics (2009) as a collection of indicators that represent the same mentioned constructs. The latent variables also prove convergent validity as the AVE extracted by the variables is above 0.5 (Hair Jr. et al., 2021). The discriminant validity of the constructs was assessed and Fornell- Larcker Criterion was employed. Table 1 shows the values for all constructs were less than 0.90, confirming the discriminant validity of the study model. Table 1 indicates that there were no collinearity issues as all the inner VIF (collinearity statistics) values were less than five (Hair Jr. et al., 2021) and even less than three (Hair, Risher, Sarstedt, & Ringle, 2019).\n\nFurthermore, prior to assessment, the structural model was assessed the bootstrap method was used to evaluate the path coefficients of the structural model. Table 2 shows the t-values, and p-values (95% bias-corrected confidence intervals were evaluated to determine the sign and significance of the path coefficients (Hair, Risher, Sarstedt, & Ringle, 2019). The value of the structural model offers no support for hypothesis H1 (Contingent Rewards ➔ Employee Performance: β = -0.026, t = 0.529, p = 0.597) and hypothesis H3 (Contingent Punishment ➔ Employee Performance: β = 0.052, t = 1.259, p = 0.208) i.e., there is no significant relationship of the direct effects of contingent rewards and punishments with employee performance.\n\nIn order to establish the presence of a mediation effect, three criteria should be met (Preacher & Hayes, 2008). Firstly, it is important to have a statistically significant association between the independent variable and the mediator. Secondly, the mediator must exhibit a statistically significant relationship with the dependent variable, even after accounting for the influence of the independent variable. Lastly, the indirect effect must attain statistical significance when subjected to rigorous assessment through a bootstrapping procedure.\n\nTable 3 shows the results of the mediation analysis estimations. Aligning with our expectations, all the subdimensions of employee engagement i.e., vigor, absorption, and dedication fully mediate the influence of contingent rewards on employee performance. One of the important conditions for any intervening variable is, that when indirect paths are controlled, the relationship between the predictor variable and outcome variable is no longer significant (Baron & Kenny, 1986). As shown in Table 3, the direct path between contingent rewards and employee performance is no longer significant (β = -0.026, t = 0.529, p = 0.597). When the path between an independent variable and a dependent variable is reduced to zero, there is a piece of strong evidence for a dominant intervening variable (Baron & Kenny, 1986). It means the perfect mediating holds when contingent rewards do not affect the employee performance of the employees when their engagement is controlled. Table 3 shows employees’ vigor (V), absorption (A), and dedication (D) as significant mediators in the relationship between contingent rewards and employee performance. In line with these results, hypotheses H2a, H2b, and H2c are accepted.\n\n* p-value less than 0.05.\n\nFurthermore, Table 4 exhibits the full mediation effect of employee vigor, absorption, and dedication in the relationship between contingent punishments and employee performance, where the direct path between contingent punishments and employee performance is no longer significant (β = 0.052, t = 1.259, p = 0.208). but the total effect between contingent punishments and employee performance is significant (β = 0.335, t = 5.550, p = 0.000). The result leads us to accept hypotheses H4a, H4b, H4c which are supported.\n\n* p-value less than 0.05.\n\n\nDiscussion\n\nThis study investigates the underlying mechanisms and conditions that explain why and under what circumstances transactional leadership style specifically the contingent rewards and punishments has impact on employee performance. Specifically, the present study represents one of the first efforts to examine the mediating role of employee engagement of non-clinical healthcare professionals in the relationship between contingent rewards, punishments, and employee performance in the Indian healthcare scenario.\n\nThe findings of the study indicate that contingent rewards did not directly forecast employee performance. However, it was observed that all components of employee engagement, namely vigor, absorption, and dedication, showed a full mediation relationship between contingent rewards and employee performance. This observation underscores the significance of employee engagement as a pivotal mechanism linking the impact of contingent rewards to the performance of employees. Notably, individuals exhibit motivation to engage in a task when they possess the confidence that their efforts will yield performance improvements (Malik, Butt, & Choi, 2015). Empirical evidence further supports the notion that rewards can exert an influence on individual behaviour, contingent upon the perceived value and relevance of these rewards to the recipients (Schwab, Olian-Gottlieb, & Heneman, 1979). The relationship between rewards and performance has been a subject of debate. It is proposed that the concept of rewards positively predicting employee performance on a situational basis is contingent upon employees possessing high levels of self-engagement and regard. Such attributes are influenced by an intrinsic locus of control, thereby enhancing employee performance (Malik, Butt, & Choi, 2015). The study underscores the significance of individuals in comprehending leadership phenomena, particularly in the context of rewards being contingent on performance. In this regard, the clarification of task requirements assumes important. In this dynamic, superiors exercise control over rewards, while subordinates employ control over performance. This reciprocal dynamic results in both parties mutually influencing and exerting control over one another (Yammarino, Spangler, & Dubinsky, 1998).\n\nFurthermore, the study’s results shed light on the impact of contingent punishments which is not directly linked to employees’ performance. Instead, this relationship is indirectly influenced through a full mediation effect involving employee engagement, encompassing factors such as vigor, absorption, and dedication, ultimately affecting employee performance. It is worth noting that punishment, as a managerial practice, possesses popularity and is not easily replaceable by alternative approaches like rewards (Baron, 2009). However, it is important to recognize that punishment can sometimes have detrimental effects on employee performance (Podsakoff, Bommer, Podsakoff, & MacKenzie, 2006). The effects of punishment on performance, though, are not straightforward, and the existing literature presents a mixed picture (Podsakoff, Todor, & Skov, 2017). It is essential for leaders to exercise careful judgment when contemplating the implementation of contingent punishment as a strategy to enhance performance. They must take into account various contextual factors, the nature of the work environment, and the specific individuals involved in the decision-making process to determine the appropriateness and effectiveness of such approach.\n\nIn this study, employee engagement assumes the role of a mediating variable, thereby coordinating the underlying mechanism that connects the influence of contingent punishments to employee performance. This finding reaffirms the notion that employees who are deeply engaged in their work are subsequently more inclined to surpass their fundamental job performance (Scrimpshire, Edwards, Crosby, & Anderson, 2023). The performance of employees is intrinsically linked to their level of engagement, as it is influenced by a multitude of external factors that converge to foster an internal orientation aimed at achieving and delivering high levels of performance. Consequently, the transactional leadership style proves effective in augmenting the performance of non-clinical healthcare professionals, primarily when the influence of contingent rewards and punishments is mediated by employee engagement. This research contributes to the advancement of our comprehension regarding the circumstances under which contingent punishment is associated with job performance. Based on the results, theoretical and managerial implications are discussed.\n\nThis research makes several noteworthy contributions to the existing scholarly literature. First and foremost, it responds to the growing demand for a deeper investigation into the various influence mechanisms inherent to transactional leadership (Zheng, Wu, Xie, & Li, 2019). This study investigates the intricate pathways connecting contingent rewards and punishments with the performance of non-clinical healthcare professionals within the hospital and healthcare sector. Prior research has demonstrated that transactional leadership behaviours are predictive of both task performance and the contextual performance of employees, mediated by constructs such as leader-member exchange (Kim & Park, 2015), and organizational commitment (Donkor & Zhou, 2020). Building upon the tenets of social exchange theory, this study extends the existing literature by examining the significance of three distinct sub-dimensions of employee engagement—namely, employee vigor, absorption, and dedication—among healthcare professionals and their consequential impact on performance within the healthcare sector.\n\nSecondly, it is worth noting that there is a limited body of research that has separately probed into the mediating roles of vigor, absorption, and dedication concerning the association between transactional leadership style and employee performance, with a specific emphasis on the contingent rewards and punishment approach (Deng et al., 2019; Yozgat & Kamanli, 2016). To the best of our knowledge, within the Indian context, there appears to be a dearth of investigations into how two distinct contingent aspects of transactional leadership style function to enhance employee job performance when employee engagement is taken into consideration. Our findings affirm the presence of full mediation effects of employee engagement in augmenting the influence of contingent rewards and punishments on employee performance within the hospital sector.\n\nThis study presents a range of managerial implications, furnishing professionals in the healthcare industry with a comprehensive framework for comprehending how non-clinical healthcare professionals perceive leadership styles and their consequent influence on job performance.\n\nFirstly, considering our research findings, it is evident that the contingent rewards and punishments approach inherent to transactional leadership does not directly yield improvements in employee performance. Transactional leadership is fundamentally structured around a system of rewards and punishments, and while it can be efficacious in certain contexts, it may not consistently translate into heightened employee performance. In response, managers are advised to consider supplementing transactional leadership with alternative leadership styles that emphasize inspiration and motivation, rather than exclusively relying on the mechanism of rewards and punishments.\n\nSecondly, it is imperative for managers to engage in a critical examination of the performance metrics employed within the context of a transactional leadership model. This assessment should encompass an alignment of these metrics with the organizational objectives, ensuring that they authentically capture the contributions made by employees. The extensive use of transactional leadership, particularly when taken to an excessive degree, can culminate in employee disengagement. Our research reveals a full mediation effect concerning employee engagement, implying that employees may become primarily engaged by external rewards while concurrently experiencing a diminishment in their intrinsic interest in their work or the overarching mission of the organization. Consequently, managers must undertake proactive measures to reignite employee engagement. In cases where employees exhibit dissatisfaction with a transactional leadership style that does not directly foster performance improvement, there is an elevated susceptibility to disengagement among the employees. Addressing this difficulty may necessitate a managerial reassessment of leadership approaches and the overall work environment.\n\nThirdly, in instances where transactional leadership fails to yield direct improvements in employee performance, it befits managers to exhibit readiness for leadership adaptation. Such adaptation should encompass the exploration of supplementary leadership styles, with a deliberate emphasis on employee engagement. Within the horizon of transactional leadership, rewards are frequently contingent upon specific, tangible outcomes. Consequently, managers may find it advantageous to broaden their range by incorporating diverse modes of recognition and appreciation, aimed at acknowledging and motivating employees, even when the immediate, direct influence on performance remains less obvious.\n\nWhile the present study exhibits robust research design, it is essential to admit certain limitations. Primarily, it is important to recognize that the research employs a cross-sectional design, which, while advantageous in elucidating associations, does not establish causal relationships with certainty. Employing longitudinal research methodologies could provide a more thorough examination of the underlying causal dynamics. Secondly, it is pertinent to note that this study predominantly focuses on analyzing the impact of transactional leadership on the performance of non-clinical healthcare professionals. Future inquiries may opt to delve into the ramifications of transformational leadership on work outcomes or performance within the healthcare domain. This broader perspective would furnish a more comprehensive and comparative understanding of leadership dynamics within healthcare contexts. Despite these acknowledged constraints, this study augments our comprehension of the determinants influencing the performance of non-clinical healthcare professionals, particularly through its emphasis on employee engagement. It underscores the pivotal role played by engaged employees within organizational contexts, thereby offering valuable insights for organizational management and leadership practices.\n\n\nConclusion\n\nThis study represents transactional leadership and its constituent components’ impact on the performance of followers, with particular attention directed towards work engagement. The results emphasize the crucial role played by leaders who utilize contingent rewards and punishments in promoting enhanced employee performance, concurrently highlighting the importance of nurturing employee engagement. Our investigation illuminates the inherent inclination of non-clinical healthcare professionals towards roles that resonate with their personal preferences, indicating a tendency towards engagement irrespective of contingent rewards and punishments. These insights underscore the organizational responsibility to offer work experiences infused with enthusiasm, thereby fostering an environment conducive to vibrant and engaged professional lives. It is important to acknowledge that employees serve as the foundational pillar of any organizational entity. Failure to provide them with opportunities for the integration of work and enjoyment within the workplace can engender an escalating sense of disengagement among the employees. Consequently, the cultivation of employee engagement should be perceived not as a single undertaking but as an ongoing, multifaceted process characterized by continual learning, refinement, and proactive measures.",
"appendix": "Data availability\n\nDRYAD: Contingent reward, punishment and employee performance. https://doi.org/10.5061/dryad.g4f4qrfwk (Layek & Koodamara, 2023a).\n\nThe project contains the following underlying data:\n\n• Data file 1.csv (273 Coded respondent’s datasheet).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nZenodo: Contingent reward, punishment and employee performance. https://doi.org/10.5281/zenodo.10225424 (Layek & Koodamara, 2023b).\n\nThis project contains the following extended data:\n\n• Blank_Questionnaire_with_likert_scale_(1).docx (Well-established measurement scales for study variables)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAbdelwahed N, Soomro B, Shah N: Predicting employee performance through transactional leadership and entrepreneur’s passion among the employees of Pakistan. 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Publisher Full Text\n\nKock N, Lynn G: Lateral Collinearity and Misleading Results in Variance-Based SEM: An Illustration and Recommendations.2012; 13: 546–580. Publisher Full Text\n\nLayek D, Koodamara N: Contingent reward, punishment and employee performance. [Dataset]. Dryad. 2023a. Publisher Full Text\n\nLayek D, Koodamara N: Contingent reward, punishment and employee performance. Zenodo. 2023b. Publisher Full Text\n\nMacKenzie SB, Podsakoff PM, Rich GA: Transformational and transactional leadership and salesperson performance. J. Acad. Mark. Sci. 2001; 29(2): 115–134. Publisher Full Text\n\nMalik M, Butt A, Choi J: Rewards and employee creative performance: Moderating effects of creative self-efficacy, reward importance, and locus of control. J. Organ. Behav. 2015; 36(1): 59–74. Publisher Full Text\n\nNguyen H, Nguyen L: Employer attractiveness, employee engagement and employee performance. Int. J. Product. Perform. Manag. 2022; 72: 2859–2881. Publisher Full Text\n\nNorthouse PG: Leadership: Theory and Practice. Sage publications; 2021.\n\nPark Y, Lim D, Kim W, et al.: Organizational Support and Adaptive Performance: The Revolving Structural Relationships between Job Crafting, Work Engagement, and Adaptive Performance. Sustainability. 2020; 12(12). Publisher Full Text\n\nPathak D, Madan P, Srivastava S: Examining the inter-relationship between leadership styles, organisational learning capability and job satisfaction: an empirical study of Indian IT companies. Int. J. Learn. Chang. 2023; 15(1): 51–69. Publisher Full Text\n\nPodsakoff M, Bommer WH, Podsakoff N, et al.: Relationships between leader reward and punishment behavior and subordinate attitudes, perceptions, and behaviors: A meta-analytic review of existing and new research. Organ. Behav. Hum. Decis. Process. 2006; 99(2): 113–142. Publisher Full Text\n\nPodsakoff N, Podsakoff P, Kuskova V: Dispelling misconceptions and providing guidelines for leader reward and punishment behavior. Bus. Horiz. 2010; 53: 291–303. Publisher Full Text\n\nPodsakoff PM, MacKenzie SB, Moorman RH, et al.: Transformational leader behaviors and their effects on followers’ trust in leader, satisfaction, and organizational citizenship behaviors. Leadersh. Q. 1990; 1(2): 107–142. Publisher Full Text\n\nPodsakoff P, MacKenzie S, Podsakoff N, et al.: Common Method Biases in Behavioral Research: A Critical Review of the Literature and Recommended Remedies. J. Appl. Psychol. 2003; 88(5): 879–903. PubMed Abstract | Publisher Full Text\n\nPodsakoff P, Todor W, Skov R: Effects of Leader Contingent and Noncontingent Reward and Punishment Behaviors on Subordinate Performance and Satisfaction. Acad. Manag. J. 2017; 25(4): 810–821. PubMed Abstract | Publisher Full Text\n\nPolitis JD: Transformational and transactional leadership enabling (disabling) knowledge acquisition of self-managed teams: the consequences for performance. Leadersh. Organ. Dev. J. 2002; 23(4): 186–197. Publisher Full Text\n\nPreacher K, Hayes A: Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav. Res. Methods. 2008; 40: 879–891. PubMed Abstract | Publisher Full Text\n\nRobbins SP, Judge TA, Vohra N: Organizational behaviour. India: Pearson; 2019.\n\nSaks AM: Antecedents and consequences of employee engagement. J. Manag. Psychol. 2006; 21(7): 600–619. Publisher Full Text\n\nSchaufeli WB, Salanova M, Roma VG, et al.: The measurement of engagement and burnout: A two sample confirmatory factor analytic approach. J. Happiness Stud. 2002; 3: 71–92. Publisher Full Text\n\nSchwab D, Olian-Gottlieb J, Heneman H: Between-subjects expectancy theory research: A statistical review of studies predicting effort and performance. Psychol. Bull. 1979; 86(1): 139–147. Publisher Full Text\n\nScrimpshire A, Edwards B, Crosby D, et al.: Investigating the effects of high-involvement climate and public service motivation on engagement, performance, and meaningfulness in the public sector. J. Manag. Psychol. 2023; 38(1): 1–20. Publisher Full Text\n\nThanh N, Quang N: Transformational, Transactional, Laissez-faire Leadership Styles and Employee Engagement: Evidence From Vietnam’s Public Sector. SAGE Open. 2022; 1–18. Publisher Full Text\n\nTyssen A, Wald A, Spieth P: The challenge of transactional and transformational leadership in projects. Int. J. Proj. Manag. 2014; 32(3): 365–375. Publisher Full Text\n\nVillagrasaa PJ, Barrada JR, Río E F-d, et al.: Assessing Job Performance Using Brief Self-report Scales: The Case of the Individual Work Performance Questionnaire. J. Work Organ. Psychol. 2019; 35(3): 195–205. Publisher Full Text\n\nXie Y, Xue W, Li L, et al.: Leadership style and innovation atmosphere in enterprises: An empirical study. Technol. Forecast. Soc. Chang. 2018; 135: 257–265. Publisher Full Text\n\nYammarino F, Spangler W, Dubinsky A: Transformational and contingent reward leadership: Individual, dyad, and group levels of analysis. Leadersh. Q. 1998; 9(1): 27–54. Publisher Full Text\n\nYandi A, Havidz H: Employee performance model: Work engagement through job satisfaction and organizational commitment (A study of human resource management literature study). Dinasti International Journal of Management Science. 2022; 3(3): 547–565. Publisher Full Text\n\nYoung H, Glerum D, McCord M, et al.: A Meta-Analysis of Transactional Leadership and Follower Performance: Double-Edged Effects of LMX and Empowerment. J. Manag. 2021; 47(5): 1255–1280. Publisher Full Text\n\nYozgat U, Kamanli A: The effect of entrepreneur’s passion and transactional leadership style on the performance of employees. Issues in Business Management and Economics. 2016; 4(2): 9–17. Publisher Full Text\n\nZheng J, Wu G, Xie H, et al.: Leadership, organizational culture, and innovative behavior in construction projects The perspective of behavior-value congruence. Int. J. Manag. Proj. Bus. 2019; 4: 1–32."
}
|
[
{
"id": "335649",
"date": "08 Nov 2024",
"name": "Shilpi Saha",
"expertise": [
"Reviewer Expertise Organization Behaviour",
"Employee engagement",
"Multiple Organizational commitments",
"Turnover intention"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article is grounded in well-established theories like Social Exchange Theory, which adds depth to its exploration of transactional leadership's effect on employee performance through employee engagement. The paper clearly addresses a significant gap by focusing on non-clinical healthcare professionals in India, which is a novel and relevant contribution to the field.\nThe chosen methodology, a non-experimental, survey-based design with a purposive sampling approach is appropriate for the research question. The study sample of 273 non-clinical healthcare professionals from NABH-accredited hospitals in Jharkhand aligns well with the research aim. 1. The methodology section is generally well-executed, though it could improve by detailing the selection criteria for participants more explicitly. 2. Additionally, while the ethical considerations are well-addressed, explaining potential survey biases and how these were managed would enhance transparency.\nWriting style : The article is well-organized, following a logical flow from the introduction and literature review to the discussion and implications. The division of findings by the mediating role of vigor, absorption, and dedication in relation to contingent rewards and punishments enhances clarity. 1. Some transitions between sections could be smoother, particularly in the results and discussion segments. Adding connecting sentences to emphasize key findings may further aid readability.\nThis study represents a strong contribution to understanding transactional leadership in non-clinical healthcare contexts. Minor refinements as suggested above will enhance its rigor and readability.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "335650",
"date": "21 Nov 2024",
"name": "Rekha Aranha",
"expertise": [
"Reviewer Expertise Organisation culture",
"STARA",
"Diversity and inclusivity",
"employee wellbeing at work"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe introduction effectively establishes the broader context of leadership in the modern business environment. There is a clear identification of the research gap and a focus on transactional leadership. The authors have made a good integration of the theoretical framework (Social Exchange Theory) with strong literature support with recent citations and clear statement of the study's novelty in the Indian healthcare context. The healthcare context is introduced too late. Consider, mentioning it earlier in the introduction explaining why transactional leadership is particularly relevant in healthcare and describing the unique characteristics of nonclinical healthcare professionals The sample frame is well-defined with sample frame (NABH-accredited private hospitals in Jharkhand). There is a clear description of the data collection process with established measurement scales The theoretical framework can be strengthened by explaining why this theory is particularly relevant to your context, connecting it more explicitly to employee engagement\nMinor Suggestions\nConsider adding recent statistics about healthcare sector growth in India to strengthen context Add more specific details about the nonclinical healthcare professional population Consider using subheadings to improve readability Explain why 273 participants are adequate for PLS-SEM Clarify why purposive sampling was chosen over other methods\nThe article is well-written, the minor changes will enhance the readability\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12856",
"date": "05 Dec 2024",
"name": "Navin Koodamara",
"role": "Author Response",
"response": "Title: Impact of contingent rewards and punishments on employee performance: the interplay of employee engagement Reviewer’s Suggestion: 1. Consider adding recent statistics about healthcare sector growth in India to strengthen context Author’s Response: We appreciate your insightful concern. The following statistical insights information has been added to strengthen the context. “The rapid growth of India’s healthcare sector highlights the urgent need for effective employee performance measurement. As of 2024, the sector is one of India’s largest employers, with a workforce of 7.5 million people. Due to a significant shortage of healthcare workers, the demand for Indian healthcare professionals is projected to double nationally and globally by 2030 (Healthcare Industry in India, 2024). This growth, driven by population increase, an aging demographic, rising healthcare costs, and technological advancements, has amplified the demand for high-quality and efficient care. Consequently, measuring employee performance is crucial to addressing these emerging challenges.” Reflected section: Acknowledging the suggestion, we have highlighted the content mentioned in the 1. Introduction” of the manuscript. Reviewer’s Suggestion:2. Add more specific details about the nonclinical healthcare professional population. Author’s Response: The authors have added the following details of the non-clinical healthcare professionals working in the various functional departments of a hospital setting. “This study focuses on non-clinical healthcare professionals who play a vital role in supporting patient care alongside clinical staff. These individuals contribute significantly to delivering high-quality healthcare by managing administrative duties, coordinating care activities, overseeing technology, and performing various other essential tasks. By prioritizing the performance of non-clinical healthcare professionals, medical practices can enhance their overall quality of care.” Reflected section: Acknowledging the suggestion, we have highlighted the content mentioned in “ 3.1. Sample and Data Collection” of the manuscript. Reviewer’s Suggestion:3. Consider using subheadings to improve readability Author’s Response: Thank you for the insights. Subheadings have been added to the “4. Results” section to produce the findings and improve readability. These are: 4.1 Assessment of measurement model 4.2 Assessment of Structural Model 4.3 Mediation effect. Reflected section: We have highlighted the subheadings mentioned in “ 4. Results” of the manuscript. Reviewer’s Suggestion:4. Explain why 273 participants are adequate for PLS-SEM. Author’s Response: We greatly appreciate your insightful consideration concerning the use of PLS-SEM. This statistical tool is endorsed for its suitability in contexts characterized by limited sample sizes (Wong, 2013). This approach facilitated the examination of hypotheses by estimating path coefficients and T-values. Reflected section: we have highlighted the content mentioned in “ 3.1. Sample and Data Collection” of the manuscript. Reviewer’s Suggestion:5. Clarify why purposive sampling was chosen over other methods Author’s Response: We appreciate the concern about the sampling technique adopted for the study. The authors has explained the intention behind choosing purposive sampling in the following way : “Purposive sampling was adopted for this study as it allows for the intentional selection of participants with specific characteristics relevant to the research focus. By targeting non-clinical healthcare professionals involved in administrative, operational, and support roles, the study ensures that the findings are designed for this group, whose experiences and challenges differ from those of clinical staff. This method enables the collection of focused and relevant insights, enhancing the specificity and relevance of the findings.” Reflected section: Acknowledging the suggestion, we have highlighted the content mentioned in “ 3.1. Sample and Data Collection” of the manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/13-102
|
https://f1000research.com/articles/13-1487/v1
|
05 Dec 24
|
{
"type": "Systematic Review",
"title": "Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis",
"authors": [
"Abdulsalam Aleid",
"Saud Nayef Aldanyowi",
"Abdulmajeed Aljabr",
"Hasan Ali Abdullah Alaidarous",
"Zainab Aleid",
"Abdulaziz Alharthi",
"Mutlaq Alsubaie",
"Lama AlOraini",
"Abdulrahman Almoslem",
"Abbas Al Mutair",
"Saud Nayef Aldanyowi",
"Abdulmajeed Aljabr",
"Hasan Ali Abdullah Alaidarous",
"Zainab Aleid",
"Abdulaziz Alharthi",
"Mutlaq Alsubaie",
"Lama AlOraini",
"Abdulrahman Almoslem",
"Abbas Al Mutair"
],
"abstract": "Background The practice of preoperative hair removal has been debated regarding its role in Surgical Site Infection (SSI) prevention. This study aimed to compare the different hair removing modalities and investigate the effect of preoperative hair removal on SSI rates.\n\nMethods A systematic review and meta-analysis were conducted according to PRISMA guidelines. Three databases—PubMed, Web of Science, and Cochrane Library—were searched for relevant studies comparing preoperative hair removal to no hair removal. Studies eligible for inclusion were randomized controlled trials (RCTs) and cohort studies reporting SSI rates. Odds ratios, mean differences, and p-values were analyzed using a random effect model.\n\nResults Seventeen studies involving 5,407 patients were included. No statistically significant difference in SSI rates was found between the hair removal and no removal groups (OR = 1.066, 95% CI 0.646–1.758, p = 0.803). When comparing clipping to no hair removal, there was no significant difference (OR = 0.967, 95% CI 0.642–1.455, p = 0.870). Razor shaving was associated with higher skin damage and slightly increased SSI risk compared to clipping but not statistically significant (OR = 0.749, 95% CI 0.346–1.623, p = 0.464). Depilatory creams, however, were favored over razor shaving (OR = 3.235, 95% CI 1.543–6.785, p = 0.002), as they were linked to less skin damage and easier application.\n\nConclusion Preoperative hair removal does not significantly impact SSI rates. Clipping appears to be a safer alternative to shaving, while depilatory creams show promise as an effective, less damaging option.",
"keywords": [
"Surgical site infection",
"hair removal",
"clipping",
"depilatory cream",
"razor shaving",
"meta-analysis."
],
"content": "Introduction\n\nSurgical site infections (SSIs) has been linked to influence patient morbidity, healthcare cost, length of hospital stays, and increased fatalities in extreme cases.1,2 The practice of removing axillary hair prior to surgery has been widely discussed and examined, particularly in relation to its impact on the rate of surgical site infections.3,4 Given the pressing need to evaluate the impact of preoperative hair removal techniques on surgical site infection outcomes, additional research has been recommended to definitively establish the effectiveness of these techniques.5,6 This systematic review and meta-analysis sought to compare the effectiveness of different pre-operative hair removing techniques in reducing the incidence of surgical site infections (SSI), with the goal of enhancing patient care and improving post-operative results.\n\n\nMethods\n\nThis systematic review and meta-analysis were carried out in strict accordance with the PRISMA 2020 guidelines (DOI: 10.6084/m9.figshare.27331266) as described by Page et al. (2021).7 The study was also registered in PROSPERO (CRD42024547805).\n\nA comprehensive electronic search for medical literature began on February 26th, 2024, to investigate the effects of hair removal versus no removal on surgical site infection (SSI) rates. Predetermined keywords ensuring high-quality and relevant results were employed, including surgical site infections, hair removal, razor shaving, depilatory creams, and preoperative therapies.\n\nThe literature search was conducted across three databases: PubMed, Web of Science (WoS), and the Cochrane Library. Truncation symbols and relevant MeSH terms were incorporated to ensure the search was comprehensive. To ensure a comprehensive and unbiased literature search, two independent reviewers employed EndNote 20 to identify and exclude duplicates from the initial search results. Reviewers then screened the remaining articles’ titles and abstracts against predetermined eligibility criteria. Subsequently, full texts of relevant articles underwent scrutiny for content quality. Any discrepancies arising during the screening process were resolved through discussion or consultation with a third party.\n\nMethodological guidelines were followed during the study selection and data collection phases to guarantee the validity and dependability of the systematic review and meta-analysis as guided by (Kim, 2023),8 and (Muka et al., 2019).9 After conducting the literature search and screening process, studies meeting the predefined criteria were selected for inclusion.\n\nTwo independent authors assessed the full texts of the articles to determine eligibility for inclusion in the systematic review and meta-analysis. In cases of disagreement regarding the inclusion of studies, a third author was consulted to resolve conflicts and achieve consensus.\n\nInclusion criteria included studies comparing preoperative hair removal with no hair removal, hair removal using razor when compared to other modalities (e.g., clipping, depilatory creams), those examining outcomes related to surgical site infections (SSIs) or complications from hair removal. Study designs included in this meta-analysis were randomized controlled trials (RCTs) and cohort studies. The target population consisted of adult patients undergoing any type of surgery, with the primary outcome being SSIs and the intervention being hair removal versus no removal. Studies were excluded if they were not in English or lacked full-text access. Also, case reports, case series, commentaries, expert opinions, review articles, systematic reviews/meta-analysis, economic analysis, cadaver studies, narrative review, and any study with less than 10 patients were all excluded.\n\nAfter the review process, the eligible studies were subjected to data extraction using a standardized data extraction form that used study characteristics to analyze data from the articles. The form specifically highlighted the methods of research adopted by each study (study designs), the sample sizes used by each study, age, sex, the specific method used to remove hair, and the results obtained. The two reviewers worked independently to retrieve the data to avoid inaccuracies in the process.\n\nThe primary outcomes focused on comparing different hair removal techniques individually against no hair removal, as well as assessing various combinations of methods, to determine which approach is most effective in preventing SSI.\n\nWe conducted a meta-analysis using Review Manager version 5.4, pooling the dichotomous variables to calculate the odds ratio (OR). A p-value of 0.05 or lower was considered statistically significant, with 95% confidence intervals (CI). Heterogeneity was assessed using I2, with significance determined by the p-value.\n\n\nResults\n\nA comprehensive search across various databases identified 6,058 initial records. After removing duplicates (n = 1,214) and non-English publications, title and abstract screening excluded 3,972 articles for irrelevance. Full-text review of the remaining studies (n = 872) identified issues like irrelevant information, invalid methodologies, and insufficient data, leading to the exclusion of 855 articles. This rigorous process yielded 17 final studies that met the eligibility criteria and were included in this systematic review and meta-analysis ( Figure 1).\n\nSeventeen studies met the eligibility criteria and were analysed for design, sample characteristics (sample size, age, gender), surgery type (e.g., abdominal, cranial), intervention methods (e.g., razor, clipping), follow-up period, and findings. The basic characteristics of the included studies are given in Table 1(extended data). Each study’s contribution to SSI prevention was assessed individually. Study designs included randomized controlled trials (RCTs), prospective RCTs, prospective comparative cohorts, prospective non-inferiority trials, and clinical trials. These studies encompassed 5,407 patients, with 265 developing SSI. Patient ages ranged from 6 months to 88 years, with a median of 44 years. The studies investigated various surgeries: cranial, spinal, abdominal, Lichtenstein hernia repair, intracranial, genital, appendectomy, chest, VP shunt insertion, and external/middle ear surgeries. Intervention methods included razor shaving, clipping, and depilatory creams. Follow-up periods varied greatly, ranging from 3 days to 10 months.\n\nThe analysis comparing hair removal versus no removal found no statistically significant difference, with an overall odds ratio (OR) of 1.066 [95% CI 0.646, 1.758; P = 0.803], and the heterogeneity was below 50% ( Figure 2). In a comparison of preoperative clipping to no hair removal, two studies, Abouzari et al. (2009)10 and Kowalski et al. (2016),11 showed no notable difference between the two methods, with an OR of 0.967 [95% CI: 0.642-1.455; P = 0.870] and no heterogeneity (I2=0.0%; P= 0.981) ( Figure 3). Additionally, when comparing hair clipping to razor shaving, the analysis favored hair clipping but indicated no statistically significant difference, yielding an overall OR of 0.749 [95% CI 0.346, 1.623; P = 0.464], with heterogeneity remaining under 50% (I2=34.363%; P= 0.179) ( Figure 4). In contrast, depilatory cream was preferred over razor shaving, resulting in an overall OR of 3.235 [95% CI; 1.543, 6.785; P = 0.002], and the heterogeneity among studies was zero (I2=0.0%; P = 0.473) ( Figure 5). Overall, the meta-analysis exhibited low publication bias, with studies showing large effect sizes across analyses. The comparison of hair removal versus no hair removal did not demonstrate any defined publication bias, as the studies were moderately scattered with minimal concentration around the mean effect size in the funnel plots. Furthermore, subgroup analysis plots revealed a few large studies that were uniformly distributed from the mean effect size ( Figures 6, 7, and 8).\n\n\nDiscussion\n\nIn recent years, numerous studies have explored the effect of preoperative hair removal on the occurrence of surgical site infections (SSIs).12–15 However, the results presented lack conclusiveness and consistency, leaving this intervention entirely obscure in the realm of surgical medicine.4,16–21 Some studies have reported a general lack of significant difference between shaved and non-shaved groups.6,14,16,22–26 Others have even reported possible risks of SSIs with razor-shaving.22,27–31 Moreover, multiple studies recommended excluding hair removal from preoperative preparation practices unless necessary.6,14,20,32\n\nPreoperative hair removal has long been considered a routine preventive treatment against surgical site infections.33 However, more current studies have revealed a contrary opinion on this event.6,15,32,34–36 The current review included studies comparing surgery with and without preoperative hair removal. The analysis found no significant difference in infection rates between the two groups. This suggests that removing hair before surgery may not offer any advantage in terms of preventing infections. Similarly, surgery with hair removal using clippers to surgery with no hair removal showed no significant difference in infection rates. These findings suggest that hair removal before surgery may be unnecessary. These findings support the results attained by Tang et al. (2001),37 and Horgan et al. (1999).38 Specifically, the study by Tang et al. (2001)37 lacked a significant difference between the shaved group and the unshaved one in all parameters that were investigated using a sample size of 90 patients. Additionally, the study by Horgan et al. (1999)38 presented no cases of SSI development in both the experimental and control groups.\n\nFurther analysis was done for the comparison groups involving different hair removal methods: shaving to clipping, shaving by using depilatory cream, and clipping by using depilatory cream. The primary outcomes were the development of SSI, whereas the secondary outcomes considered damage to the skin, effectiveness of hair removal, cost of the method, and simplicity of the procedure associated with each method in hair removal. In this meta-analysis, six studies were reviewed to compare hair clipping with razor shaving for preoperative hair removal.27,39–43 The meta-analysis revealed no clear advantage between the two methods, though the results slightly favored clipping. Notably, in the razor shaving group, significant skin damage was observed, which increased the likelihood of surgical site infections (SSIs) due to the compromised integrity of the skin. A comparison of razor shaving and depilatory cream was conducted using data from four studies aimed at evaluating the two methods.40,44–46 The findings revealed notable differences between them, with depilatory creams being generally preferred. Depilatory creams were found to offer greater ease of use, cause less skin trauma, and ensure effective hair removal. Due to these advantages, depilatory cream is recommended over razor shaving for preoperative hair removal, as it is linked to reduced skin damage and a lower risk of surgical site infections (SSIs). In a study conducted by Turhan et al. (2022), depilatory creams were compared to hair-clipping techniques. The researchers concluded that there was no significant difference between the two methods in terms of their effectiveness for hair removal. This similarity was observed in both the overall results and the effect size analysis.40\n\nThe overall heterogeneity in these meta-analyses was relatively low, with moderate variation observed in the primary comparison of hair removal versus no hair removal and the analysis of shaving. This variation may stem from differences between the individual studies. For example, studies with comparable sample sizes, follow-up durations, and participant demographics, such as sex, tended to produce more consistent results. On the other hand, studies with greater differences in these factors showed higher levels of heterogeneity.47,48\n\nThe traditional belief that preoperative hair removal reduces infection has been challenged in recent years.6 Contrary to this long-held view, recent studies, including findings from our meta-analysis, indicate that hair removal may not be essential, as there was no significant difference in infection rates between patients who underwent hair removal and those who did not. The study also suggests that if hair removal is needed, using clippers is better than shaving with a razor.6 Razors may increase the risk of infection by causing nicks and irritation. Depilatory creams seem like a promising alternative because they remove hair without damaging the skin, but more studies are needed on their long-term effects.49\n\nSeveral limitations were observed in studies investigating the connection between preoperative hair removal and SSIs. One key issue was the inconsistency in the quality of the evidence, with some studies not utilizing proper blinding or control groups. Additionally, many studies were constrained by small sample sizes. These shortcomings highlight the need for more robust studies to better understand the effect of preoperative hair removal on SSIs. Future studies should focus on well-designed randomized controlled trials (RCTs) that implement standardized hair removal techniques and include larger patient populations to clarify its role in SSI prevention.\n\n\nConclusion\n\nThis systematic review and meta-analysis revealed no substantial difference in surgical site infection (SSI) rates between patients who had preoperative hair removal and those who did not. However, razor shaving was linked to a higher risk of SSIs when compared to clipping, but it was not statistically significant. Clipping emerged as the preferred method for hair removal when necessary, while depilatory creams showed promise as a potential alternative to shaving. These results question the conventional view that preoperative hair removal prevents infections, suggesting it should be avoided unless deemed necessary.\n\n\nEthical statement\n\nNot applicable as this review involves already published studies and no ethical issue.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\nRepository name: Figshare, Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis, DOI: https://doi.org/10.6084/m9.figshare.27331266.v2.50\n\nThis project contains the following data:\n\n- Table 1: Basic characteristics of included studies\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nRepository name: Figshare, Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis, DOI: https://doi.org/10.6084/m9.figshare.27331266.v2.50\n\nThis project contains the following data:\n\n- PRISMA_hair removal_checklist\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgment\n\nThe authors acknowledge the Deanship of Scientific Research at King Faisal University for obtaining financial support for research, authorship, and the publication of research under Research Proposal Number (KFU241652).\n\n\nReferences\n\nHou Y, Collinsworth A, Hasa F, et al.: Incidence, and impact of surgical site infections on length of stay and cost of care for patients undergoing open procedures. Surg. Open Sci. 2023 Jan 1; 11: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCostabella F, Patel KB, Adepoju AV, et al.: Healthcare cost and outcomes associated with surgical site infection and patient outcomes in low-and middle-income countries. Cureus. 2023 Jul; 15(7). Publisher Full Text\n\nOkoli CC, Anyanwu SN, Emegoakor CD, et al.: Does preoperative chemical depilation make any difference in postoperative wound infection? Niger. J. Clin. Pract. 2020 Sep 1; 23(9): 1318–1323. PubMed Abstract | Publisher Full Text\n\nDohmen PM, Konertz W: A review of current strategies to reduce intraoperative bacterial contamination of surgical wounds. GMS Krankenhhyg. Interdiszip. 2007; 2(2). PubMed Abstract\n\nEdmiston CE Jr, Leaper DJ, Barnes S, et al.: Revisiting perioperative hair removal practices. AORN J. 2019 May; 109(5): 583–596. PubMed Abstract | Publisher Full Text\n\nTanner J, Melen K: Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst. Rev. 2021; 8(8): Cd004122. PubMed Abstract | Publisher Full Text\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372.\n\nKim G: How to perform and write a systematic review and meta-analysis. Child Health Nurs. Res. 2023 Jul; 29(3): 161–165. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuka T, Glisic M, Milic J, et al.: A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research. Eur. J. Epidemiol. 2020 Jan; 35: 49–60. PubMed Abstract | Publisher Full Text\n\nAbouzari M, Sodagari N, Hasibi M, et al.: Re: Nonshaved cranial surgery in black Africans: a short-term prospective preliminary study (Adeleye and Olowookere, Surg Neurol 2008;69-72) Effect of hair on surgical wound infection after cranial surgery: a 3-armed randomized clinical trial. Surg. Neurol. 2009; 71(2): 261–262. PubMed Abstract | Publisher Full Text\n\nKowalski TJ, Kothari SN, Mathiason MA, et al.: Impact of hair removal on surgical site infection rates: a prospective randomized noninferiority trial. J. Am. Coll. Surg. 2016 Nov 1; 223(5): 704–11. PubMed Abstract | Publisher Full Text\n\nJacob KR, Markose A, Mathew A, et al.: A randomized controlled trial to compare the effects of two methods of preoperative hair removal on surgical site infections in patients undergoing elective tympanoplasty. J. Evol. Med. Dent. Sci. 2018 Sep 10; 7(37): 4095–4101. Publisher Full Text\n\nWaltz PK, Zuckerbraun BS: Surgical site infections and associated operative characteristics. Surg. Infect. 2017 May 1; 18(4): 447–450. Publisher Full Text\n\nShi D, Yao Y, Yu W: Comparison of preoperative hair removal methods for the reduction of surgical site infections: a meta-analysis. J. Clin. Nurs. 2017 Oct; 26(19-20): 2907–2914. PubMed Abstract | Publisher Full Text\n\nLefebvre A, Saliou P, Lucet JC, et al.: Preoperative hair removal and surgical site infections: network meta-analysis of randomized controlled trials. J. Hosp. Infect. 2015 Oct 1; 91(2): 100–108. PubMed Abstract | Publisher Full Text\n\nDhamnaskar S, Mandal S, Koranne M, et al.: Preoperative surgical site hair removal for elective abdominal surgery: does it have an impact on surgical site infection? Surg. J. 2022 Jul; 08(03): e179–e186. Publisher Full Text\n\nUçkay I, Harbarth S, Peter R, et al.: Preventing surgical site infections. Expert Rev. Anti-Infect. Ther. 2010 Jun 1; 8(6): 657–670. Publisher Full Text\n\nHranjec T, Swenson BR, Sawyer RG: Surgical site infection prevention: how we do it. Surg. Infect. 2010 Jun 1; 11(3): 289–294. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHijas-Gómez AI, Lucas WC, Checa-García A, et al.: Surgical site infection incidence and risk factors in knee arthroplasty: A 9-year prospective cohort study at a university teaching hospital in Spain. Am. J. Infect. Control. 2018 Dec 1; 46(12): 1335–1340. Publisher Full Text\n\nNiel-Weise BS, Wille JC, Van Den Broek PJ: Hair removal policies in clean surgery: systematic review of randomized, controlled trials. Infect. Control Hosp. Epidemiol. 2005 Dec; 26(12): 923–928. PubMed Abstract | Publisher Full Text\n\nTucci G, Romanini E, Zanoli G, et al.: Prevention of surgical site infections in orthopaedic surgery: a synthesis of current recommendations. Eur. Rev. Med. Pharmacol. Sci. 2019 Apr 2; 23.\n\nKose G, Tastan S, Kutlay M, et al.: The effects of different types of hair shaving on the body image and surgical site infection in elective cranial surgery. J. Clin. Nurs. 2016 Jul; 25(13-14): 1876–1885. PubMed Abstract | Publisher Full Text\n\nRojanapirom S, Danchaivijitr S: Pre-operative shaving and wound infection in appendectomy. J. Med. Assoc. Thai. 1992 Mar 1; 75 Suppl 2: 20–23. PubMed Abstract\n\nLee DH, Yoo S, Shin E, et al.: Nonshaved ear surgery: effect of hair on surgical site infection of the middle ear/mastoid surgery and patients’ preference for the hair removal. J. Audiol. Otol. 2018 Jul; 22(3): 160–166. PubMed Abstract | Publisher Full Text\n\nKattipattanapong W, Isaradisaikul S, Hanprasertpong C: Surgical site infections in ear surgery: hair removal effect; a preliminary, randomized trial study. Otolaryngol. Head Neck Surg. 2013 Mar; 148(3): 469–474. Publisher Full Text\n\nLee YH, Kwon YS, Cho JM: Ventriculoperitoneal Shunt without Hair Shaving Using Absorbable Suture Materials. J. Korean Neurosurg. Soc. 2021; 64(1): 120–124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVaria DM, Kacheriwala S: Pre-operative shaving versus trimming and their relation to post-operative surgical site infection (SSI), a randomized controlled trial. Int. J. Res. Med. 2016; 5(3): 151–154.\n\nSeidelman JL, Mantyh CR, Anderson DJ: Surgical site infection prevention: a review. JAMA. 2023 Jan 17; 329(3): 244–252. Publisher Full Text\n\nLove KL: Patient care interventions to reduce the risk of surgical site infections. AORN J. 2016 Dec 1; 104(6): 506–515. Publisher Full Text\n\nÇelik SE, Kara A: Does shaving the incision site increase the infection rate after spinal surgery? Spine (Phila Pa 1976). 2007; 32(15): 1575–1577. PubMed Abstract | Publisher Full Text\n\nWalia DS, Saini JR, Mohi RS, et al.: Shaving before Surgery-Merits & Pitfalls. Ann. Int. Med. Dent. Res. 2021; 7(1): 24.\n\nSmall SP: Preoperative hair removal: a case report with nursing implications. J. Clin. Nurs. 1996 Mar; 5(2): 79–84. PubMed Abstract | Publisher Full Text\n\nMarecek GS, Weatherford BM, Fuller EB, et al.: The effect of axillary hair on surgical antisepsis around the shoulder. J. Shoulder Elb. Surg. 2015 May 1; 24(5): 804–808. PubMed Abstract | Publisher Full Text\n\nViera V: Preoperative skin antisepsis. Medicina Intensiva. Med. Intensiva (Engl Ed). 2018 Nov 5; 43: 18–22. Publisher Full Text\n\nRichards A, Zaben M, Patel C, et al.: The need for hair removal in paediatric brain tumor surgery? Br. J. Neurosurg. 2024 Mar 3; 38(2): 346–348. PubMed Abstract | Publisher Full Text\n\nThapa N, Basukala S, Regmi SK, et al.: Postoperative surgical site infection after preoperative use of razor versus clipper for hair removal in inguinal hernia surgery: A quasi-randomized clinical trial. Health Sci. Rep. 2024 Jan; 7(1): e1830. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTang K, Yeh JS, Sgouros S: The Influence of Hair Shave on the Infection Rate in Neurosurgery: A Prospective Study. Pediatr. Neurosurg. 2001 Jul 1; 35(1): 13–17. PubMed Abstract | Publisher Full Text\n\nHorgan MA, Kernan JC, Schwartz MS, et al.: Shaveless brain surgery: safe, well tolerated, and cost-effective. Skull Base Surg. 1999; 9(04): 253–258. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdeleye AO, Olowookere KG: Nonshaved cranial surgery in black Africans: a short-term prospective preliminary study. Surg. Neurol. 2008 Jan 1; 69(1): 69–72. PubMed Abstract | Publisher Full Text\n\nTurhan VB, Topcu R, Yıldız A: Is there any difference between shaving versus clipping versus depilatory gel of hair removal for skin preparation before surgery in respect of wound infection? J. Health Sci. Med. 2022 Mar 3; 5(2): 564–567. Publisher Full Text\n\nGrober ED, Domes T, Fanipour M, et al.: Preoperative hair removal on the male genitalia: clippers vs. razors. J. Sex. Med. 2013 Feb; 10(2): 589–594. PubMed Abstract | Publisher Full Text\n\nMarul F, Aygın D: Evaluation of the Effect of Two Different Hair Removal Methods Before Surgery on Surgical Site Infections. Gazi Med. J. 2021 Jul 1; 32(3). Publisher Full Text\n\nOmolabake BI, Ozoila KN: A comparison of postoperative wound infection rates after preoperative hair removal with razors versus clippers in a suburban setting. Int. Surg. J. 2020 Oct 23; 7(11): 3627–3632. Publisher Full Text\n\nAdisa AO, Lawal OO, Adejuyigbe O: Evaluation of two methods of preoperative hair removal and their relationship to postoperative wound infection. J. Infect. Dev. Ctries. 2011 Oct 11; 5(10): 717–722. PubMed Abstract | Publisher Full Text\n\nPowis SJ, Waterworth TA, Arkell DG: Preoperative skin preparation: clinical evaluation of depilatory cream. Br. Med. J. 1976 Nov 13; 2(6045): 1166–1168. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSuvera M, Vyas P, Patel M, et al.: Two methods of pre-operative hair removal and their effect on post-operative period. Int.J. Med. Sci. Pub. Health. 2013 Oct 1; 2(4): 885. Publisher Full Text\n\nLinden AH, Hönekopp J: Heterogeneity of research results: A new perspective from which to assess and promote progress in psychological science. Perspect. Psychol. Sci. 2021 Mar; 16(2): 358–376. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGlasziou PP, Sanders SL: Investigating causes of heterogeneity in systematic reviews. Stat. Med. 2002 Jun 15; 21(11): 1503–1511. Publisher Full Text\n\nAnderson DJ, Podgorny K, Berríos-Torres SI, et al.: Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect. Control Hosp. Epidemiol. 2014 Sep; 35(S2): S66–S88. PubMed Abstract | Publisher Full Text\n\nAljabr A: Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis. figshare. Figure. 2024. Publisher Full Text"
}
|
[
{
"id": "346927",
"date": "10 Jan 2025",
"name": "Aygin Dilek",
"expertise": [
"Reviewer Expertise surgical nursing"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aims to compare different hair removal methods and investigate the effect of preoperative hair removal on SSI rates. Keywords were determined according to PICOS and A systematic review and meta-analysis were conducted according to PRISMA guidelines. The number of databases was limited to three. Was grey literature reviewed or excluded? It should be stated. Randomized controlled trials (RCTs) and cohort studies reporting SSI rates were included. Rate ratios, mean differences and p values were analyzed using a random effects model. However, the quality scores of these articles are not clear. What was used as a quality assessment tool? A table showing the quality scores given to the articles should be added.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": []
},
{
"id": "353578",
"date": "13 Jan 2025",
"name": "Francesk Mulita",
"expertise": [
"Reviewer Expertise colon cancer",
"thyroid cancer",
"obesity",
"complications"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to congratulate the authors on their fascinating work regarding this interesting report entitled “Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis”. The manuscript is well-written and the incorporated figures make the study easy to follow. I strongly recommend acceptance for indexing of the paper after minor revision. 1) I would like a brief discussion on SSI as a postoperative complication after colorectal surgery 2) The SSI is the most common postoperative complication after colorectal surgery, causing pain and suffering to patients. In addition, this complication has been associated with negative economic impact, increased morbidity, extended postoperative hospital stay, readmission, sepsis, and death. I would suggest adding this important information to the discussion section and consider citing the recently published articles Mulita F, et al., 2022 [Ref-1] Panos G, et al., 2021 [Ref-2] 3) I want a brief discussion on complications after colorectal surgery, and the use of new enzymes such as Butyrylcholinesterase levels as a predictive marker for complications after this procedure. Consider citing the recently published article on a new biomarker (Buche): Verras GI, Mulita F, 2024 [Ref-3]\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1487
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https://f1000research.com/articles/13-1485/v1
|
05 Dec 24
|
{
"type": "Research Article",
"title": "Network and sentiment analysis of Enron emails",
"authors": [
"Natnael Belay"
],
"abstract": "Background The objective of the research was to analyze e-mails exchanged at Enron, a power company that declared bankruptcy in 2001 following an investigation into unethical operations regarding their financials.\n\nMethods Like other researchers, we identify the “most important” employees and detect “communities” using network science methods. In addition, because previous work required that 10 e-mails be sent and received for an e-mail relationship to exist, we analyzed the effect of different “thresholds” on the results. We also performed sentiment analyses on the e-mails to evaluate whether sentiment changed over time.\n\nResults We find that the “importance” of a person depends on the centrality measure used; while the communities we detected resembled the formal organizational structure of the company. In addition, we found that centrality results were very dependent on the “threshold” used. Finally, analysis of email sentiment over time = do not give insight into the financial wellbeing of Enron.\n\nConclusion Our results provide insight into how information flowed through Enron, who the key employees were, and e-mail sentiment before and after the crisis.",
"keywords": [
"Sentiment analysis",
"Natural language processing",
"Pattern recognition",
"Text analysis"
],
"content": "I. Introduction\n\nFor an organization, understanding how employees communicate is very important. For example, it can help managers understand the culture of the organization better. Of the possible communication mechanisms, e-mail is the most popular. Managers may need to know how a particular message they sent is being passed around among the employees. Apart from managers in an organization, other people might be interested in e-mail communication from a social science perspective. In addition, analyzing e-mail communication can allow us to see the general sentiment of the e-mails being exchanged. Enron was chosen to perform this analysis because of the availability of corporate e-mails to the public. Enron was a power company that declared bankruptcy in 2001 following an investigation into unethical operations regarding their financials. By analyzing the contents of the Enron e-mails, and how e-mails are passed around, we can get an understanding of the social structure of a company and can identify the influencers of that employee network. The research also looks at whether the sentiment of the e mails corresponds to Enron’s financial well-being.\n\nThe objective of the research was to analyze e-mails exchanged at Enron using concepts from Network Science and using Python programming to understand the informal organizational structure and the culture at Enron over time. To achieve our objective, we analyzed the Enron e mail corpus obtained from William Cohen of Carnegie Mellon University. We wrote scripts that traversed the e-mails, parsed out the necessary parts of the e-mails and conducted sentiment and network analysis. For the network analysis, we used different centrality measures to deduce the importance of a node (employee), and for the sentiment, we used TextBlob and Matplotlib to calculate and visualize the sentiment trend. Gephi was used as a visualization and centrality measuring tool. As part of this research, we provide three different Python modules, sentimentAnalysis.py, edgeListGenerator.py, and parseE-mails.py, on Github that can be used to conduct a similar analysis.\n\nOur main findings are as follows:\n\n• We find the ranking of the “most important” employees differ between the different centrality measures. We also find that the definition of a legitimate e-mail communication has an impact on the rankings of the employees.\n\n• We find that the sentiment trend of the Enron e-mails does not reflect their financial troubles.\n\nResearchers have investigated how the communication network can be analyzed to give insight into who the “most important” employees were, and how the structure of the network changes overtime. They have found that the communication network gets denser during the financial crisis of Enron.4 In addition, they have found that different centrality measures give different results as to who the “most important” employee was.4\n\nThe rest of this section is divided into the following sections: Section 2 contain background information and summary of previous related work, Section 3 describes the methods, Section 4 contains the results obtained from the methods, and Section 5 concludes the paper.\n\n\nII. Background and related work\n\nEnron was a power company based in Houston, Texas and was co-founded in 1985 by Jeffrey Skilling and Kenneth Lay. Originally, the company started as a merger between two pipeline companies, Houston Gas and Omaha-Base InterNorth.1 In 1988, deregulations for electrical markets were put in place and Enron became creative in order to increase profits in the newly deregulated market. The first action Enron took was to change their business model from “Energy delivery” to “Energy broker”. That change allowed them to be market creators by bringing power demanders and sellers together. When a transaction takes place, Enron got paid the difference of the amount buyers paid and sellers requested.2 The change in revenue model made Enron very successful financially and fed the culture of challenging limits.\n\nIn the 1990’s Enron was one of the first companies to use the internet for their business operations.3 The infusion of a strong energy company with a huge financial power and a presence on the internet built the confidence of investors which led their stock price to reach $90 per share and made the company worth over $70 billion.3 The leadership of Enron actively promoted a culture of competition among employees and challenged everyone to match the standards that were being continually raised. Even though it seems that always striving to do better equates to success, there are some limitations that need to be respected in order to be within the limits of the law. Employees that worked at Enron have disclosed that the main focus of the Enron managers was to add value to their outputs, and to deliberately break rules to see how far they could get away with it.2 As expected, this culture brought very serious issues in 1999. It was revealed that Enron had numerous partnerships with companies (known as special purpose entities) that they created,4 and it became clear that Enron was using those entities to separate the company’s losses of $618 million and its debts in order to show profits on their balance sheets. That action inflated Enron’s profits which misled investors. The Security and Exchange Commission (SEC) began an investigation on October 31, 2001. The investigation revealed that Enron had a loss of $586 million for the previous five years. That news impacted the stock price which fell below $1 per share. Due to this financial loss, Enron filed for bankruptcy in December 2001.4\n\nAs part of the investigation, the Federal Energy Regulatory Commission (FERC) released a database of Enron e-mails in May 2002.4 It is the only corporate e-mail corpus available to date for the public. The original database included 619,449 e-mails from 158 Enron employees which accounted for 92% of the Enron staff. The database contained the e-mail addresses of the sender and the recipient, date, time and body of the e-mail. This version of the database was not optimized for research and researchers have since restructured the data. The first modification was provided by Jitesh Shetty and Jafar Adibi from the Inter-service Intelligence (ISI). This version contained 252,759 e-mails from 151 employees. The e-mails in this version were placed in a MySQL table with different columns for different parts of the e-mail such as body and recipient. The version of data that was used in our research was from William Cohen from Carnegie Mellon University (CMU).4 This version contains 517,431 distinct e-mails from 151 employees.4 The database size is 423 MB, and the e-mails are stored as text files. This version was chosen because the data integrity issues are solved.\n\nA network is a relationship composed of nodes and links between those nodes. For example, a network could be employees and their relationships with each other. A node is an entity that is a subject or a target that performs an action in the network. For example, a node can be an employee that sends an e-mail in an organization. A link is a connection between nodes. For example, the e-mail sent from one employee to another links those subjects in the network. A network can be defined as a directed or undirected network. A directed network is a network where the links between the nodes indicate the directional flow of information. In a directed network, node can be a source of information and or a receiver of information (or both). An example of a directed network is the World Wide Web (WWW), where a web page has one or more links to other pages.5 In our research, we used a directed network. Undirected networks are networks that have links which support the bi-directional transmission of information. An example of an undirected network is a power grid, where transmission lines transmits electricity in both directions.5 In this case, a node would be a power plant and the link would be the transmission wires. An illustration of an undirected and directed network can be seen in Figure 1 where the directed network has arrows at the end of the links and the undirected network has no arrows.\n\n1) Overview of centrality measures\n\nOnce the network is defined, numerous measurements can be made. Centrality measures are used to identify the most “important” or “influential” node(s) in a network, and include closeness centrality, degree centrality, betweenness centrality, eigenvector centrality, and PageRank. Because the centralities will measure different aspects of a node, the analyst has to decide which measures are appropriate for the question asked. The next section gives a background on the meanings and calculations of each of the above measures. Within a single network, there might be different nodes that are of highest importance depending on the centrality measure. Those nodes are illustrated in Figure 2.\n\n2) Degree centrality\n\nThis Figure reproduced from https://docs.arangodb.com/3.2/Manual/Graphs/Pregel/.6\n\nDescription: Degree centrality calculates how many nodes a single node is directly connected to. It is the number of connections a node has to other nodes. The node that has the highest degree centrality is the node that is connected to the most nodes.5 In a directed network, there are two types of degree centrality measures. The first one is the in-degree centrality. It measures how many links point to the node. The other is out-degree centrality and it measures how many links point out to other nodes from that particular node. This measure is calculated for each node and a list of nodes in descending order of degree centrality is usually presented. The mathematical formula for degree centrality can be found in Ref. 6.\n\nInterpretation: If one node has more direct connections than all other nodes, then this node may have more reach. From an organizational point of view, a person with the highest out-degree centrality disseminates information to a larger group of employees than anyone else. If an employee has a large in-degree centrality, they might be receiving a lot more information about the organization than anyone else. That information access can make them an integral part of an organization.\n\n3) Closeness Centrality\n\nDescription: Closeness centrality is a measure of how close a node is to all other nodes,5 based on the shortest distance of a node to every other node. The shortest distance is the minimum number of links needed to connect two nodes. A node that has a small average distance from all other nodes will have a higher closeness. After calculating closeness centrality for one node, the process can be repeated for all nodes to get a value for each of them. The final values can then be sorted in descending order to rank the importance of each node based on its closeness centrality. The formula for calculating closeness centrality is given by Ref. 5 and is\n\nInterpretation: This measure can be indicative of an important person because it measures their reach to all other nodes. In an organizational setting, a person with a high closeness centrality can reach more of the employees in the organization with less relative effort. In other words, that person has the resources to get information from or to multiple employees quickly.\n\n4) Betweennes Centrality\n\nDescription: Betweenness centrality is another measure in network analysis that calculates how many times a node is on the shortest path between different nodes.5 Therefore, a node with high betweenness serves as an information broker for transferring data among nodes. This can be calculated as follows as in Ref. 5 using the formula\n\nWhere Zi is the betweenness centrality of node i , σjk is the number of shortest paths from j to k and σjk(i) is the number of those paths that go through node\n\nInterpretation: Nodes with high betweenness have the power to control the exchange of information among employees because information passes through them to reach others quickly. These nodes can alter, block or facilitate information that is critical to the overall functioning of the network. If a network loses a node with a high betweenness centrality, then the information flow may become less efficient. In an organizational setting, an employee with high betweenness might be crucial for transferring important information such as company policies from one department to another.\n\n5) PageRank and eigenvector centrality\n\nDescription: Eigenvector centrality and PageRank are very similar in how they calculate a node’s importance based on the importance of the nodes that the node is connected to. However, they have their differences, and PageRank is considered to be a better measurement for a directed network than eigenvector centrality.7 In eigenvector centrality, a node’s centrality is calculated by how connected they are to nodes with higher importance. Therefore, they get their value from the properties of their connections. This centrality gives value to each node proportional to the sum of scores of its neighbors.7 For eigenvector centrality, all the nodes inherently have 0 importance until they make a connection. PageRank is a similar concept but here all the nodes inherently have a certain β value, and the neighbor’s importance is equally divided among its neighbors. Therefore, a node that is connected to more important nodes gets a higher rank. In addition, the formula of PageRank includes division by out-degree. This helps to keep nodes with high centrality from passing values to other nodes disproportionality by normalizing the value.7 PageRank is a measure that Google uses to rank the relevance of webpages retrieved from a Google search. The formula for both eigenvector centrality and PageRank uses an adjacency matrix. An adjacency matrix is a matrix where the elements are defined as follows: if there is a direct link from node j to node i , the value is 1; otherwise, the value is 0.\n\nThe eigenvector centrality x of node i is given by xi=∑j∈VAijxj where j is a neighbor of, Aij is an element of the adjacency matrix and xj is the eigenvector centrality of node i\n\nThe PageRank y of node i is yi=α∑j∈VAijKjyj+β where α , β are positive constants, α+β=1 , β>0 , kj is the out-degree of a page (or node) V is the set of all the nodes and j is a neighbor of i and is an element of V(j)∈V. 5 For more details, see Ref. 5\n\nInterpretation: When nodes are connected to other important nodes they will have the power to influence or get information from these important nodes and therefore are themselves important. In an organization, an employee that has more contact with managers may be considered important because of his/her link with important people. In this research, in addition to the other centrality measures, we also used PageRank, which to our knowledge has not been used for detecting important people at Enron. An example PageRank is shown in Figure 3 where the sizes of the nodes correspond with their respective PageRank value.\n\n6) Community detection\n\nDescription: Community detection is another concept in Network science that aims to identify subsets of nodes that are more connected with each other than they are connected with other subsets. One method to identify communities is Modularity.5 In this method, the network of nodes is divided into n random partitions.5 Then, nodes are moved from one partition to another while recording the change in Modularity. If the Modularity of the network increases when a node is moved to a different partition, then it suggests that the node belongs in that partition. The community structure that results in the highest Modularity measure is considered to be the optimal partition.5 Refer to Ref. 7 for the formula to calculate Modularity.\n\nInterpretation: Because community detection identifies subsets of nodes that are more connected with each other than they are connected with others, the process can be used to identify “real life” e-mail communities at Enron, which will help understand the company’s organizational structure and culture.\n\n7) Sentiment analysis\n\nDescription: Sentiment analysis is an area of Natural Language Processing (NLP) that quantifies the emotional content of text. Generally, sentiment is categorized as positive, neutral or negative. One of the tools that can be used for conducting sentiment analysis is a Python module named TextBlob which also provides a simple API for conducting text analysis tasks such as part-of speech tagging, noun phrase extraction, classification, and more. TextBlob uses a predefined set of words in a dictionary (lexicon) that are assigned subjectivity, intensity, polarity (sentiment values), position in a sentence (part-of-speech), and a short description (called sense). A single word might have multiple sense, therefore complicating the sentiment calculation. This lexicon is an open source XML document that can be found in the following link https://github.com/sloria/TextBlob/blob/eb08c120d364e908646731d60b4e4c6c1712ff63/textblob/en/en-sentiment.xml.8\n\nCalculation\n\nSingle Words: At the core, Text Blob uses averaging to calculate the polarity of words. For instance, the word great has four senses (possible meaning), as a result having four different polarity values in the lexicon.8 To get a concrete answer, the four polarity measures are averaged together to result in a polarity of 0.8.8\n\nNegations: Whenever TextBlob encounters a negation, it multiplies the polarity by −0.5 leaving the subjectivity and other measures unchanged.8 For instance, the polarity of “not great” would change to −0.4 because 0.8×−0.5=−0.4. 8\n\nModifiers: Modifiers, like very, will have an impact on the polarity and subjectivity of the of the word. In case of modifiers, the intensity of the modifier is used to multiply the polarity and subjectivity of the of the word.8 For instance, “Very Great” would have a different sentiment than just “great”. Here the intensity of “very” is 1.3.8 Thus, both the sentiment and the subjectivity would be multiplied by 1.3.8 Since both the subjectivity and polarity have a value that ranges between −1 and +1, any value that is outside the boundary would be set to either numbers depending on the sign of its value. Therefore, “very great” would have a polarity of 1 (even though its true value is 1.04) and a subjectivity of 0.975.8\n\nNegations and modiiers: it is possible that there are phrases that have both modifiers and negations. For instance, the word “not very great”. In this case, the calculation is somewhat similar to the above calculations. The polarity would be multiplied by -0.5 for the negation.8 But then, for the modifier, instead of multiplying the intensity as it is, the inverse intensity is multiplied for both the polarity and subjectivity.8 Therefore, the polarity of “not very great” would be the result of 11.3×−0.5×0.8=−0.31 . The subjectivity would be 11.3×0.75=0.58. 8 Single words and unknown words: When TextBlob encounters a single letter word or a word that is not in the lexicon, it will simply ignore it by assigning a zero value. For longer sentences, TextBlob averages the values of the sentiments for each words or phrases.\n\nKlimt and colleagues worked on automated classification of e-mails to user created folders based on Natural Language Processing (NLP),9 using the CMU version of Enron’s e-mail database. The research objective was primarily to classify, by folders, e-mails by looking at the “To”, “BCC”, “CC”, and “From” fields, using Support Vector Machines (SVMs). They conducted their analysis by feeding e-mails to the SVM with each of the 4 fields listed above separately and all the fields together as a bag of words.9 They then calculated the F1 score (a measurement based on the precision and recall) and determined which fields are most important for automated e-mail classification. Their research found that the performance of the classifier depends on the folder creation strategy of the user. The more folders a user has the more accurate the SVM classification. The limitation of this research is that it is specific to the Enron e-mail dataset and the performance of the SVM depends on the organization of a user’s folders, which are determined by each user.\n\nDiesner and colleague studied the Enron e-mail data set to explore the communication network.4 Their primary goal was to compare different network science measures before and after the crisis at Enron occurred. They specifically compared October of 2000 to October of 2001, which was around when the Enron crisis broke out. They used the dataset provided by Shetty and Abidi from ISI but added a layer to the dataset by introducing information on the positions of the Enron employees. They named this instance of the data set the Enron CASOS database. They segmented the data into monthly e-mail exchanges so that there is a detailed view of the change of communication that occurred within the years. They fed the data to an Organizational Risk Analyzer (ORA), so that they can visualize the change in the clustering of e-mail exchange among agents.\n\nThey defined a relationship between agents as an e-mail being sent between them at least once. As expected, October 2000 had a less dense network as compared to October 2001. They calculated different network analysis measures for the two time periods to identify the top five agents. They looked at the measures closeness centrality, betweenness centrality, eigenvector centrality, in-degree centrality, and out-degree centrality. Each of those measures came up with different employees as having high measures and the employees with the highest measures also changed their standing between 2000 and 2001. For instance, they found that in October 2000 the person with the highest closeness centrality was the manager W. Stuart. However, in 2001 an employee named S. beck had the highest closeness centrality. An important limitation with4 is that they used a single e-mail as a criterion for an e-mail relationship. Therefore, e-mail relationships may be based on error messages, spams or one-time e-mail exchanges that are not representative of the true e-mail relationship structure. Our research compared and analyzed different e-mail thresholds to define an e-mail relationship. In addition, we used at PageRank algorithm, which is considered better than eigenvector centrality for directed graph.\n\nShetty and colleagues used a different methodology to deduce the most important agent.10 They used the order (peace) of a network in order to see what node disturbs the overall graph the most when removed. For this purpose, they used Graph Entropy to calculate the order of the Graph. They used the e-mail corpus provided by ISI which is stored in a MySQL database. They used one e-mail between agents in order to establish an e-mail relationship. After that, they carried out two distinct iterative processes of removing each node from the graph and recording the change in Graph Entropy. One of the processes was concerned with removing nodes and links that are directly connected to the node, links that are at a distance of one link from each other. The second process was removing each node and its directly linked links and in addition links that have used the node as a transit, links that are at a distance of two links from each other. The node that had the highest change in entropy was the most important. The top five nodes with highest disturbance were recorded for both processes. In length=1, they found out that the most important person was Louise Kitchen, Enron ex-president. On length=2, they found out that Greg Whalley, Enron ex-president, to be the most important. They concluded that length=2 gives a more realistic answer because the reach of an employee usually stretches more than their immediate contacts. The limitation of this research is that they did not consider removing links that are more than a length of two. The reach of some employees might be more than two links and10 ignores those employees. They also did not provide any justification to why they chose a length of two.\n\nJoshua and colleagues studied the methods of automatic community detection using e-mails gathered from HP labs.11 They used the Girvan Newman algorithm to identify communities. Their research was based on 1 million e-mails gathered within a period of 2 months from November 25, 2002 to February 18, 2003. However, that dataset was cleaned by removing messages sent to a list of more than 10 recipients, as these e-mails were often lab wide announcements, which consisted of 185,773 e-mails. From the e-mail content, only the “To” and “From” fields were used in order to facilitate the identification of communities while keeping the privacy of the agents. The definition that they applied to define an e-mail relationship was that a person had to send at least 30 e-mails and get at least 5 back from the same person. That definition helps to create a relationship network where the communications are legitimate. They used the non-local process of partitioning a network into subsets by using betweenness centrality. This process helps visualize any nodes that have links to other subsets and suppresses them in that subset if they have more links in the subset that outside of it. The method involves repeatedly identifying intercommunity links and removing them until the giant component is resolved into many separate communities. Their algorithm stops removing links once the number of vertices in a subset equals 6. That is because to have a viable component of more than one community, there needs to be at least 6 vertices in both communities combined connected to each other by a single link. If the link is removed, the components vanish, and the vertices become part of the same community. In partitioning a large connected component of vertices, instead of using every vertex as the “center\" once, they cycled through the network randomly by choosing M centers instead of all vertices becoming centers. This process was carried out until the betweenness of a link exceeded the betweenness of the leaf node. They then remove the link with high betweenness (meaning it connected components). This process is repeated until the entire graph was separated into communities. This process keeps a running total of how many times each vertex appeared in a community on each round. If there were n rounds and a vertex appeared in a community n times, it suggests that the particular vertex belongs in that community. If the running total of the vertices is smaller than n it means that it is also related to other communities. In this research, they only used the “To” and “From” fields from the e-mails to construct the network structure. In our research, in addition to the “To” and “From” fields, the “CC” and “BCC” fields were also be used to create a more accurate representation of Enron. The community detection algorithm that was used was the Modularity.\n\nPage and colleague ranked the importance of webpages using the PageRank algorithm.12 They built a repository of 24 million webpages through complete crawling and indexing as part of the Stanford WebBase project. They converted the URLs to integer ID’s, stored the links in a database with the integer ID serving as a unique identifier, and removed dangling (dead-end) links. As part of the PageRank calculation, every node, in this case every web page, gets a rank. PageRank runs through the database iteratively until it converges and assigns the natural rank of a webpage. PageRank is also related to the “Random Walk” probability, which is the probability that a random walker, or a random user, ends up at a certain webpage. They used PageRank for page searching, similar to what Google does. Following a title search, they are able to get an accurate list of pages that are logically related to the search term. This paper demonstrates PageRank, which was used in our research.\n\n\nIII. Methods\n\nThe e-mail corpus is downloaded as a set of folders and text files using a Windows Personal Computer. The network diagram is based on the e-mail corpus where a node is an agent and a link is an e-mail relationship between agents.\n\nOur first step was to reproduce the results obtained by the work of Diesner and K. Carley in understanding Enron’s network structure.4 In that effort, we first retrieved all the edge lists that were included in the dataset. We used the Python programming language to read through the e-mail messages and retrieve the different sections of each e-mail. To be added to the edge list, we required the individuals in the “From”, “To”, “CC”, and “BCC” fields to have a folder in our dataset. The filtering process was conducted using an SQL analysis in Microsoft Access. Once that filter was set, the number of employees we had data on was 146.\n\nWe then inputted the filtered list into Gephi. We also added the positions of the employees that were ranked. For the position data, we used an external source, from University of Edinburgh School of Informatics, which had the employee names along with their positions.13 We parsed our dataset and performed another SQL analysis in Microsoft Access that counted the number of employees that correspond to each position. Finally, we produced communication networks using Gephi by inputting the edge list. PageRank algorithm was used as a criterion to size the nodes. For the analysis, only the “sent”, “_sent_mail”, “sent_items” e mail folders were utilized.\n\nWe changed the number of e-mails that were required to be exchanged between two employees (threshold). We performed similar analysis as above (reproduction of previous research) by changing the definition of a legitimate e-mail communication between two employees (threshold). We defined the thresholds at different points, 0, 5, and 10 e-mails sent from one employee to another. Gephi’s filtering function was used to filter for different edge weight’s by keeping the minimum degree value at a constant value of one. The edge weight filter was a subquery of the degree number filter in Gephi. The different rankings of the employees from October 2000 where plotted.\n\nTo conduct the sentiment analysis of the e-mails, a Python package called TextBlob was used. Once the files are located and the body of the e-mail extracted, the TextBlob package was invoked to give a numerical representation of the sentiment of each e-mail. For this research, in order to know the change of sentiment over time, the e-mail sent date was parsed out using Python programming as the sentiment of the same e-mail was being calculated. An average of the sentiments for each month was calculated and plotted in a graph using the Matplot package of Python to visualize the change in sentiment over time.\n\nTwo different graphs were produced as part of the analysis. The first line graph showed the time series trend of the sentiment on the organizational level. From it, we statistically compared the average sentiment values for October 2000 and October 2001. The second line graph showed a time series trend of the sentiment for every user.\n\nFor our analysis, we used the modularity community detection algorithm that is provided by Gephi. It calculates the modularity values of each nodes and assigns them to a class. Thus, a class corresponds to community. We then color coded the different classes to create a visual representation of the different communities. Within Gephi, ForceAtlas2 with a Strong Gravity was used as a layout option for the network.\n\n\nIV. Results\n\nAs part of this research, we have developed three Python modules to help researchers analyze the Enron e-mail dataset. They are available in the following Github repository: https://github.com/NatnaelA/thesis. They are described as follows:\n\nparseEmail.py: This module is the foundation of the all the other modules because it helps to extract different values from the e-mails. The sections extracted are “From”, “To”, “CC”, “BCC”, “Subject”, “Body”, and “Date”. The module allows the user to specify which of those fields they want to recover. Multiple selections are also supported. From this module, a user can select to parse the email of a single e-mail, a single employee folder, or all the employees included in the data set. A user can also specify the start and end date of the e-mails to focus on.\n\ngenerateEdgeList.py: This module builds on the parseEmail.py module to use the “From”, “To”, “CC”, and “BCC” fields to create an edge list. It has the capability to generate an edge list for a single email, for a single employee, or all the employees in the data set. A user can specify the start and end date of the e-mails to focus on.\n\nsentimentAnalysis.py: This module builds on the parseEmail.py module; however, it has additional components. Like the other modules, it allows the calculation of the sentiment for a single email, a single employee or all the employees included in the data set. A user can also specify the start and end date of the e-mails to focus on. In addition, this module completes execution by returning a sentiment trend graph. The user can choose to select a line graph or a box plot to see the time series trend of the sentiment at Enron. The default is a line graph.\n\n\n\n1) Enron e-mail data corpus\n\nThe specific dataset used has a significant impact on the results that will be revealed. Analyzing the dataset gave us a strong foundation to interpret our results. In an effort to reproducing earlier research, we summarized the number of filtered employees associated with each position and compared it to other data sets. The reason for filtering is that we wanted to get an accurate representation of the conditions inside Enron. The unfiltered dataset would have e-mails sent to outsiders, like family and friends, which would add noise to our analysis. We found that there were similar positions across the datasets. However, there are differences in the count, and some datasets had unique positions. That is mainly due to the existence or nonexistence of certain employees from the data sets. Table 1 shows the summary statistics of the employee.\n\n2) Centrality measures\n\nAs an effort to check the validity of the results presented by the work of Diesner and K. Carley in understanding Enron’s network structure,4 we performed a similar analysis where we calculated the centrality measures of the employees and we ranked them. We used Gephi to construct the network and measure the centralities of the employees and rank them in descending order of their values. Our results, show that using different centrality measures leads to different results regarding who is the most important person. For instance, for October 2001, Eigenvector Centrality has John Lavorato, the CEO, as the employee with the highest value, but Betweenness Centrality had Louise Kitchen, the President, as the most important employee. This is understandable because Betweenness Centrality measures how often an employee, is in the middle of the shortest path between other pairs of employees. On the other hand, Eigenvector Centrality gives a value to a node according to the importance of the other nodes that it is connected to. For this step, we defined an e-mail communication (threshold) as at least one e mail sent between employees. Refer to sections 3.2 and 4.3 for more information on thresholds. In addition, our results differed from.4 Even though the two analyses had common individuals, there are a few that are unique to either dataset. Since most centrality measures give value to a node relative to the other nodes, the non-existence of a node will affect the centrality measure of the other nodes. For instance, eigenvector gives a value to a node depending on the value of the node that it is connected to. Thus, if A has a higher value (importance), B will also have a higher value if it connects with A. However, if A is not in the dataset, the value of B will be reduced which will then affect its ranking.\n\n3) Network Structure\n\nIn Figure 4, The sizes of the nodes differ due to the ranking of the nodes according to the PageRank algorithm. Consistent with4 which explored the network structure of the Enron organization through the emails, it can be seen that the network in October of 2001 is denser and more connected than the network for October 2000. In October 2000, the number components were 84. In October 2001, the number components were 72. A component is a set of nodes where all pairs of nodes have paths connecting them. Thus, as the number of components increases, the graph becomes more disconnected because there will be numerous subgraphs. For a cohesive network, the total number of components should be lower. Thus, in October 2001, it can be seen that the number of components was reduced indicating that the more nodes are becoming part of a single component, as a result more cohesive. This is understandable because employees would be communicating more during a crisis.\n\nBecause previous work by Shetty and Adibi required that 10 e-mails be sent and received for an e-mail relationship to exist, and Ref. 4 had none, we analyzed the effect of different “thresholds” on the results and found that results were very dependent on the “threshold” used. A threshold is the minimum number of e-mails that need to be sent to define a link. From Network Science perspective, this threshold is a lower bond for an edge weight of the network. We were interested in comparing the effect of different thresholds on the centrality measures and thus on the ranking of the employees. The result was that the definition of a threshold had an impact on the centrality measures of employees, and as a result altered the ranking of importance. The different thresholds used were 0 (no threshold), 5, and 10. Gehpi’s filtering functionality was used to apply the threshold. The edge weight filter was a subquery of the degree number filter. This would mean that first, all the nodes that have at least a degree value of one will be filtered (send at least one e-mail). Then out of those results, the edge weight filter will choose the edges with a certain value of an edge weight we have specified. The motivation behind this is to produce a real relationship because if employees send a higher number of e-mails among each other, there is a higher probability that there is a professional e-mail relationship between them. This threshold filters out connections where employees only send a few e-mails to each other on certain occasions and where there is no real profession Pal relationship between them. The 0 threshold was performed in the previous section (section 4.2) while reproducing the work of Diesner and K. Carley in understanding Enron’s network structure.4 The maximum edge weight (most e-mails sent to an employee) for October 2000 was 44 by Eric Bass, Trader, and for October 2001 was 89 by Jeff Dasovich, Government Relations Executive.\n\n1) Threshold impact on ranking\n\nTo visualize how the rankings of each employees change with threshold, we plotted a graph that shows the progression of the ranking across thresholds (0, 5, 10). By increasing the threshold, some employees were unranked for that specific threshold because they were either filtered out by the requirement or they were not ranked high enough for that threshold because most of their links disappeared. Once they are unranked, they do not reenter the top 5 for another threshold. The maximum edge weight (most e-mails sent to an employee) for October 2000 was 44 by Eric Bass, Trader, and for October 2001 was 89 by Jeff Dasovich, Government Relations Executive.\n\n2) Impact of threshold on the network\n\nThreshold change also had an impact on the network structure. The change resulted in the disappearance of nodes from the network, which impacted the centrality measures of the other nodes. As a result, our results show that as the threshold increased the network becomes less dense and there are multiple island networks that resulted from the disappearance of edges in the filtering processes. These characteristics was also seen in October 2001.\n\n3) Community detection\n\nWe use Gephi for community detection based on Modularity. All nodes with the same colors are in the same community. From our analysis, we discovered that the community formed was similar to the formal organizational hierarchy. For instance, we analyzed the overall community structure with a closeup to a specific community and found that the identified individualsworked in the same field: the legal issues. Table 3 shows the names and the positions of the employees.\n\n4) Sentiment analysis\n\nAfter observing that the number of e-mails sent was much higher around the crisis, we were motivated to conduct a sentiment analysis to analyze if there is a similar change in the sentiment of the e-mails. By using TextBlob, we parsed and analyzed the body of the e-mails by keeping track of the sentiment scores. TextBlob compares each word in the e-mail with a pre-defined dictionary of words (lexicon), included with TextBlob, that have a sentiment scores associated with them. The overall sentiment of a longer sentence is average of the words or phrases that TextBlob recognizes. We use TextBlob for sentiment analysis, as described in Section 2.4.7. We used matplotlib to plot the sentiments. Two graphs were constructed: the first one being a sentiment graph on the organizational level, shown in Figure 6, and a second one was a graph on a employee level, shown in Figure 7. On the organizational level, the trend fluctuated around a single point for a significant amount of time which made our result inconclusive, however; on the employee level, there are users who had strong sentiment (either positive or negative). For instance, Bradely Mckay, Contractor, had the highest average positive sentiment in December of 2000. The increase in sentiment on December 2000 could be related to Jeff Skilling replacing Kenneth Lay as the CEO. In the same month, the stock hit a 52-week high of $84.87.14\n\nWe also performed a similar analysis on the sentiment of the e-mails that are filtered (shown in Figure 6). These e-mails were sent between employees that we had data for.\n\nComparing the October 2000 and October 2001 sentiment results in both Figure 5 and Figure 6 gave a counter-intuitive result.\n\nFigure 7 Sentiment trend on an employee level.\n\nWe first assumed that as the crisis approached, the sentiments of the e-mails would decrease. However, it can be seen that the average sentiment in October 2000 was lower than the sentiment in October 2001. Quantitatively, the sentiment for October 2001 was 72% higher than October 2000 with a P-Value less than 0.05 (the result is not due to chance). Figure 8 shows the difference in the average sentiment between the two years. Thus, it was concluded that the e-mail sentiments did not represent the financial crisis that Enron was experiencing.\n\nSource: https://commons.wikimedia.org/wiki/File:Enron_closing_stock ,_1997-2002.svg.15 This figure/table has been published under creative commons by the Enron Securities Litigation.\n\nNoticing this result, we compared the sentiment trend along with the trend of the stock price in Figure 8. Our comparison produced that there was no correlation between the sentiment of the e-mails and the stock price.\n\nRelating the sentiment analysis result to the result of the number of e-mails sent, it can be seen that there is also no relation. Meaning, the increase the number of e-mails sent during a period does not give us an indication of the trend of the sentiment. For instance, in Figure 1A, there is a peak of number of sent e-mails in April 2001. However, looking at the organizational sentiment graph, Figure 6, the change in the sentiment is not noticeable, it only changed by 0.025 going from 0.075 to 0.1.\n\n\nV. Limitations\n\nThe research has some data integrity issues regarding the e-mail corpus. Since the corpus was not built to specifically answer the questions raised in this paper, some e-mails might be irrelevant for the analysis. For instance, some e-emails might be spams that should not be representative of the organizational structure. Additionally, the e-mail corpus only contains emails of 92% of the Enron ex-employees. This limits the results of the research not to be 100% accurate. In addition, our analysis is done on Enron sent e-mails collected between 1998 and 2002. Due to that, we would be missing received e-mails and other received e-mails that have been moved to another folder. Finally, the TexBlob module uses averaging to calculate the polarity of the e-mails and thus lacks context. Therefore, some e-mails might have inaccurate sentiment readings.\n\n\nVI. Conclusion\n\nE-mail is one of the most popular communication mediums for employees in the work place. Using those e-mails, one can construct a communication network structure that gives insight into to how information flows through the organization and the overall culture. With this motivation, we conducted a network and sentiment analysis where we tried to see who the “most important” person was, the change in sentiment of the e-mails sent at Enron overtime, and how changing the definition of an e-mail relationship affected the results. Like previous researches, we found that different network science measures gave different people as the “most important”. We also found that the network science measurements were sensitive to alternative definitions of e-mail relationships (thresholds); we used thresholds of 0, 5, and 10. In addition to the threshold, the calendar year in consideration had impact on the ranking of the employees. During the crisis, October 2001, the network was denser indicating that employees were communicating more. Due to the change in the character of the network, the rankings of the employees also changed between October 2000, a year before the crisis, and October 2001. As a result, researchers should be careful when choosing threshold values and the calendar year because they would have a significant impact on their result. Community detection using Gephi has allowed us to distinguish six different communities: Senior Manager for Traders, Executive Team, Traders, ENS Gas East, ENS Gast West, Associates in Trading, and the Legal team. Finally, we find that a sentiment analysis of the e-mails does not give indication in to the financial status of Enron. The average sentiment in October 2001 was actually higher than October 2000 with a P-value of less than 0.05. The sentiment trend also does not correspond to the trend of Enron stock price.\n\nNot applicable. Used publicly available Enron email corpus",
"appendix": "Data availability\n\nThe Enron email corpus was collected from Carnegie Mellon University. It can be found at https://www.cs.cmu.edu/~enron/. The data was publicly distributed by William W. Cohen to benefit researchers. Here is a direct quote from the data source owners: “I am distributing this dataset as a resource for researchers who are interested in improving current email tools, or understanding how email is currently used”. This statement is published at https://www.cs.cmu.edu/~enron/. This email corpus was made public by the United States Federal Energy Regulation Committee during their investigation of Enron. Here is the first public release made by the FERC: https://www.ferc.gov/electric/industry-activities/addressing-2000-2001-western-energy-crisis/information-released-enron-investigation\n\nCode used to analyze enron emails can be used at https://github.com/NatnaelA/thesis. This code was written entirely by the author of this research.\n\n\nReferences\n\nEnron Fast Facts - CNN. [Accessed: 22-Oct-2018]. Reference Source\n\nSims RR, Brinkmann J: Enron Ethics (Or: Culture Matters More than Codes). J. Bus. Ethics. Jul. 2003; 45(3): 243–256. Publisher Full Text\n\nNPR: Fall of Enron. [Accessed: 22-Oct-2018]. Reference Source\n\nDiesner J, Carley K: Exploration of Communication Networks from the Enron E-mail Corpus. Proceedings of Workshop on Link Analysis, Counterterrorism and Security, SIAM International Conference on Data Mining. 2005; 2005: pp. 3–14.\n\nBarabási A-L: Network Science by Albert-László Barabási. BarabásiLab; [Accessed: 31-Oct-2018]. Reference Source\n\nRoy S: Network analysis and applications Sushmita Roy BMI/CS 576 Dec 2nd, ppt download. [Accessed: 27-Oct-2018]. Reference Source\n\nNewman MEJ: Networks: An introduction. Oxford: Oxford University Press; 2018.\n\nSchumacher A: TextBlob Sentiment: Calculating Polarity and Subjectivity.07-Jun-2015. [Accessed: 24-Oct-2019]. Reference Source\n\nKlimt B, Yang Y: The Enron Corpus: A New Dataset for E-mail Classification Research. Machine Learning: ECML 2004. Boulicaut J-F, Esposito F, Giannotti F, et al., editors. Berlin, Heidelberg: Springer Berlin Heidelberg; 2004; vol. 3201. : pp. 217–226.\n\nShetty J, Adibi J: Discovering important nodes through graph entropy the case of Enron e-mail database. Proceedings of the 3rd international workshop on Link discovery - LinkKDD’05, Chicago, Illinois. 2005; pp. 74–81.\n\nJoshua T, Wilkinson D, Huberman B: E-Mail as Spectroscopy: Automated Discovery of Community Structure within Organizations: The Information Society: Vol 21, No 2. [Accessed: 27-Oct-2018]. Publisher Full Text\n\nPage L, Brin S, Motwani R, et al.: The PageRank Citation Ranking: Bringing Order to the Web.11-Nov-1999. [Accessed: 22-Oct-2018]. Reference Source\n\nUniversity of Edinburgh School of Informatics. [Accessed: 24-Oct-2019]. Reference Source\n\nTimeline: A chronology of Enron Corp. The New York Times. 18-Jan-2006. [Accessed: 24-Oct-2019]. Reference Source\n\nA Brief History of Enron – With Enron Stock Chart. [Accessed: 24-Oct-2019]. Reference Source"
}
|
[
{
"id": "348356",
"date": "28 Dec 2024",
"name": "Sezai Tunca",
"expertise": [
"Reviewer Expertise İşDünyası",
"Teknoloji ve İnovasyon",
"BlockchainDijital Dönüşüm",
"RNN",
"Twitter",
"Uygulamalı Yapay Zeka",
"Doğal Dil İşleme",
"Metin Analizi",
"Metin Analizi",
"Metin İşleme",
"Sözcüksel Anlambilim",
"Büyük Veri Analizi",
"Nicel ve Nitel Araştırma",
"Tematik AnalizSınıflandırma Algoritma"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study comprehensively analysed the Enron email database, providing valuable insights into both network structure and sentiment trends, and developed tools that support methodological diversity and reproducibility. A detailed analysis of the organisational structure using community sensing methods and centrality measures, and an effective presentation of the data through visual representations, is commendable. However, the limited data set and the fact that noise such as spam can affect the analyses limited the scope of the study. While simple sentiment analysis methods such as TextBlob do not sufficiently take context into account, the lack of a more in-depth examination of the lack of relationship between sentiment and financial status stands out as a shortcoming. Furthermore, the focus of the analyses on a specific time period (2000-2001) and the limited generalisability of the results to different sectors narrowed the scope of the findings. The apparent influence of different threshold values on the results may increase methodological sensitivity and question reliability. Despite these weaknesses, the study can be considered as having built a strong foundation by conducting a comprehensive analysis on the Enron database.\nTo strengthen this study, more accurate analyses can be made by improving data quality, such as filtering out noise, contextualising sentiment analysis using advanced NLP models (e.g. BERT or VADER), and comparisons with data sets other than Enron. In this way, the performance of the method used in the study can be evaluated. Thus, the results of the study can become more reliable. In addition, time series analyses can be extended to examine in depth the relationships between e-mail intensity, stock prices and crisis dynamics; dynamic network analyses and extended thresholds can be used in this process. To present the findings more effectively, interactive visualisation tools can be used, information flows between community structures can be detailed, and generalisability can be increased by benchmarking across different sectors. Finally, since internal correspondence has an official meaning, it may cause employees to use email correspondence within certain constraints. Employees may not want to write their real feelings on company e-mails and this may cause bias in emotion measurement.\nIn general, I found the study sufficient and it can be indexed if the deficiencies I mentioned are revised.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1485
|
https://f1000research.com/articles/13-1484/v1
|
05 Dec 24
|
{
"type": "Case Report",
"title": "Case Report: Large mediastino-abdominal hydatid cyst extending through the Larrey's hiatus: A rare case report",
"authors": [
"Houssem Messaoudi",
"Habib Bessrour",
"Mokhles Lajmi",
"Wafa Raghmoun",
"Wael Ferjaoui",
"Mohamed Bechir Khalifa",
"Saber Hachicha",
"Houssem Messaoudi",
"Mokhles Lajmi",
"Wafa Raghmoun",
"Wael Ferjaoui",
"Mohamed Bechir Khalifa",
"Saber Hachicha"
],
"abstract": "Background The extension of hydatid liver cysts into the mediastinum through diaphragmatic hiatus is extremely rare. In this report, we describe a rare case of a hydatid liver cyst with mediastinal extension through Larrey’s hiatus, emphasizing the surgical strategy for successful treatment. In this report, we present the first documented case of a hydatid liver cyst extending into the mediastinum through Larrey’s hiatus.\n\nCase presentation We report the case of a 65-year-old male who presented with right-upper-quadrant and left-sided chest pain evolving for two months. Physical examination showed dullnes in the epigastric region. A thoraco-abdominal CT scan, revealed a 13 cm mediastino-abdominal hydatid cyst, centered on the left liver lobe with extension into the mediastinum through the Larray’s diaphragmatic hiatus. The patient underwent surgical management. Both thoracic and visceral surgeons were involved. The surgical management involved both thoracic and visceral surgeons. A Makuuchi incision allowed resection of the hydatid liver cyst. The mediastinal portion of the cyst, resting on the pericardium was aspirated through Larrey’s hiatus, followed by irrigation with a scolicidal solution. The postoperative course was uneventful.\n\nConclusion Transmediastinal hydatid liver cysts are rare and should be operated on in close collaboration between visceral and thoracic surgeons to prevent complications.",
"keywords": [
"hydatid cyst",
"liver",
"mediastinum",
"Larrey's hiatus."
],
"content": "Introduction\n\nHydatidosis is an anthropozoonosis due to the development of the larval form of taenia echinococcus granulosis in humans.1 Echinococcal cysts involve predominately the liver (60–70%) and the lungs (15%). It arises in other abdominal organs in 10% of cases.2 While the hepatic involvement is well-documented, cases of hydatid liver cysts extending into the mediastinum through a diaphragmatic hiatus are exceedingly rare.3\n\nThis unusual presentation poses unique diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management.\n\nWe report herein a rare case of a 65-year-old man with a hydatid cyst involving the liver and the mediastinum with anatomical continuity through the Larry’s hiatus.\n\nThis case highlights the importance of a well-planned surgical approach and close multidisciplinary collaboration for successful intervention.\n\n\nCase presentation\n\nA 65-year-old male patient, without past medical history, presented with right upper quadrant pain, associated with left-sided chest pain and epigastric discomfort evolving for two months. Physical examination showed dullnes in the epigastric region. The laboratory findings were normal. Chest radiography revealed a mediastinal widening. Abdominal sonography revealed a large type IV hydatid cystic, necessitating further characterization through a computed tomography (CT) scan. Serological tests detected the presence of anti-hydatid cyst antibodies,\n\nComputed tomography showed a 13 cm cystic mass centered on the left lobe of the liver, extending into the mediastinum through the Larry’s hiatus, coming to rest intimately on the pericardium with broad contact (Figure 1). Furthermore, a calcified cyst was noted in the spleen.\n\nThe patient underwent surgery performed by a dual team of thoracic and visceral surgeons. The approach involved a Makuuchi incision ( Figure 2). During exploration, a large hydatid cyst was identified at the hepatic dome with mediastinal extension through Larrey’s hiatus. Resection of the protruding dome was performed, followed by aspiration of the hydatid fluid. An aspiration catheter was introduced through the orifice of the transmediastinal extension to evacuate the hydatid content. An irrigation with a scolicidal solution was performed. The procedure was concluded with an omentopexy into the remaining cavity. The calcified hydatid cyst of the spleen was preserved.\n\nThe postoperative course was uneventful. The patient was discharged well on oral albendazole with a posology of 400 mg per day for six months. No recurrence was observed after one year of follow-up.\n\n\nDiscussion\n\nHydatid disease remains a significant public health concern in Mediterranean countries such as Tunisia.1 The most frequent location are the liver and the lung. The mediastinal location is extremely rare, with anecdotal reports in the literature accounting for less than 1 % of cases.4 In the majority of cases, the mediastinal hydatid cyst is unique.5 The simultaneous involvement of the liver and mediastinum by a single hydatid cyst is an extremely rare condition.3 A classification was established by Gomes et al. on the transdiaphragmatic extension of hydatid liver cysts, but it did not specify the extension through diaphragmatic hiatus.6\n\nTo the best of our knowledge, this exceptional case of hydatid liver cyst extending to the mediastinum through Larry’s hiatus, represents the first ever documented in the literature, underscoring its extreme rarity. Lahdhili M reported a case of a gigantic mediastino-abdominal hydatic cyst extending through esophageal hiatus.3\n\nThe physiological thoraco-abdominal pressure gradient suggests that the cyst likely originated primarily in the liver, with its anterior mediastinal extension occurring through a weakness in the anterior diaphragmatic muscle, which must be the Larrey’s hiatus. Most patients with mediastinal hydatid cyst are symptomatic.7\n\nThe presenting symptoms depend on the cyst’s size, location, and the extent of compression or erosion of adjacent mediastinal structures. In our case the patient presented with a two month right upper quadrant pain, associated with left-sided chest pain and epigastric discomfort. Mediastinal hydatid cysts can lead to serious complications, such as rupture, fistula development, infection, and pressure on vital structures.7\n\nImaging investigations play a major role in the detection of hydatid liver cysts. The diagnostic imaging evaluation is based on multiple modalities imaging, including ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). In our case, the diagnosis was made based on the sonographic findings and scan data.\n\nThe differential diagnoses may include cystic lymphangioma, enteric cyst, bronchogenic cyst, and pleuro-pericardial cyst.8\n\nSurgery remains the optimal treatment modality of hydatid liver cyst, typically involving resection of the protruding dome. However, the mediastinal extension through Larry’s hiatus made the procedure more challenging, requiring close collaboration between thoracic and visceral surgeons. The standard treatment for mediastinal hydatid cysts typically involves pericystectomy, which includes the removal of the germinal membrane via a thoracic approach. In cases where the cyst’s localization and its invasion of vital structures complicate total excision, partial pericystectomy is recommended after the germinal membrane has been removed.5 For liver hydatid cysts, an abdominal approach can be effectively employed, even when there is transdiaphragmatic extension into the thoracic cavity.6\n\nIn our case, we opted for an abdominal approach, starting with the resection of the protruding dome of the cyst, followed by aspiration of the hydatid fluid through a Makuuchi incision.\n\nThe primary objective was to minimize surgical risks when dealing with cysts closely adhering to critical structures such as the esophagus or pericardium. Alternative strategies may involve solely performing a thoracotomy or combining both thoracotomy and laparotomy in a single surgical session.9\n\nOur decision to take this route was to address the hydatid cyst of the liver while also assessing for any potential biliary fistula. This approach allowed us to aspirate the cyst contents from the mediastinal side and inject a scolicidal solution, aiming to manage the infection effectively while minimizing the risk of complications.\n\n\nConclusion\n\nSurgical intervention remains the most effective treatment to prevent complications associated with hydatid cysts. The extension of hydatid liver cysts into the mediastinum through the diaphragmatic hiatus is indeed an atypical presentation that requires careful planning. This scenario often necessitates collaboration with visceral surgeons to determine the optimal surgical access route and technique.\n\nIn addition to surgical management, complementary adjuvant pharmacological therapy is essential to reduce the risk of recurrence. This combined approach enhances treatment efficacy, addressing both the immediate surgical needs and the long-term management of the disease.\n\n\nEthics and consent\n\nEthical approval and consent were not required.\n\n\nConsent to publish\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient.\n\nCorresponding author\n\nCorrespondence to Habib Bessrour.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nMessaoudi H, Zayène B, Ben Ismail I, et al.: Bilateral pulmonary hydatidosis associated with uncommon muscular localization. Int. J. Surg. Case Rep. 2020; 76: 130–133. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLaasri K, Zhim M, Naggar A, et al.: Hydatid cyst of the liver invading the inferior vena cava. Radiol Case Rep. 2023; 18(12): 4341–4344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLahdhili H, Lajmi M, Ragmoun W, et al.: Gigantic Mediastino-Abdominal Hydatic Cyst Through Esophageal Hiatus. Ann. Thorac. Surg. 2020; 110(6): e477–e479. PubMed Abstract | Publisher Full Text\n\nEroğlu A, Kürkçüoğlu C, Karaoğlanoğlu N, et al.: Primary hydatid cysts of the mediastinum. Eur. J. Cardiothorac. Surg. 2002; 22(4): 599–601. Publisher Full Text\n\nel Haj NI , Boubia S, Ridai M: Mediastinal hydatid cyst: an unusual case report. J. Vis. Surg. 2021; 7. Publisher Full Text\n\nGómez R, Moreno E, Loinaz C, et al.: Diaphragmatic or transdiaphragmatic thoracic involvement in hepatic hydatid disease: Surgical trends and classification. World J. Surg. 1995; 19(5): 714–719. Publisher Full Text\n\nTraibi A, Atoini F, Zidane A, et al.: Mediastinal Hydatid Cyst. J. Chin. Med. Assoc. 2010; 73(1): 3–7. Publisher Full Text\n\nÖdev K, Arıbaş BK, Nayman A, et al.: Imaging of Cystic and Cyst-like Lesions of the Mediastinum with Pathologic Correlation. J Clin Imaging Sci. 2012; 2: 33. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFreixinet JL, Mestres CA, Cugat E, et al.: Hepaticothoracic transdiaphragmatic echinococcosis. Ann. Thorac. Surg. 1988; 45(4): 426–429. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "348544",
"date": "17 Dec 2024",
"name": "Imane Boujguenna",
"expertise": [
"Reviewer Expertise pathology",
"histology",
"cancer",
"biopathology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of the Article: The article presents an exceptionally rare case of a hydatid liver cyst extending into the mediastinum through Larrey's hiatus. The authors provide a comprehensive account of the case, highlighting the surgical approach adopted to achieve successful treatment. General Impression: The article is well-written and offers valuable insights into a unique medical phenomenon. The description of the case, along with the surgical strategy, is thorough and informative. This report contributes significantly to the literature on hydatid disease by documenting a rare occurrence and offering practical surgical guidance. Strengths: - Originality: The documentation of the first case of a hydatid liver cyst extending into the mediastinum through Larrey's hiatus adds originality and novelty to the medical literature. - Clarity and Detail: The case description is clear and detailed, providing readers with a comprehensive understanding of the patient’s condition and the surgical approach taken. - Clinical Relevance: The emphasis on the surgical strategy offers practical insights that could benefit clinicians encountering similar cases. - Illustrations: The inclusion of imaging studies and surgical photographs (if applicable) enhances the reader's comprehension and provides visual evidence supporting the text. Suggestions for Improvement: - Literature Review: A more extensive review of existing literature on similar cases or related conditions could strengthen the context and significance of this case report. - Discussion on Alternatives: Including a discussion on potential alternative surgical strategies and their associated risks and benefits could add depth to the surgical approach section. - Post-operative Follow-up: Detailed information on the patient's post-operative follow-up and long-term outcomes would provide a more complete picture of the treatment’s effectiveness. Conclusion: This article is a valuable addition to the field of medical literature on hydatid liver cysts. The documentation of such a rare case and the detailed surgical strategy are commendable. With minor improvements, this case report has the potential to serve as a critical reference for clinicians and surgeons dealing with similar medical conditions.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "348550",
"date": "27 Dec 2024",
"name": "Zengru Xie",
"expertise": [
"Reviewer Expertise Clinical and basic research on skeletal echinococcosis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI read this case report with interest, and the authors indeed reported a case of a thoracic echinococcal cyst with rare anatomical features. I believe this contributes to our understanding of the disease, especially in demonstrating the dissemination range of echinococcosis. However, referring to the CARE principles for case reports, I noticed that it lacks some content that I am particularly interested in:\n1. The patient's susceptibility factors are hardly mentioned. We do not know about the patient's living environment, lifestyle, or whether they raised livestock. Is this patient a native or an immigrant? Epidemiological information is crucial.\n2. Did the patient only undergo a CT scan? If the report could describe and display ultrasound or MRI features, it would undoubtedly enhance the manuscript, especially in the context of extensive involvement. I believe it is necessary to conduct a thorough examination of all body organs, including the bones.\n3. The authors need to inform us through intraoperative observations whether the cysts originating from the liver had any implantation or adhesion phenomena in the diaphragm, pericardium, etc., or if they were merely \"transient.\" Did the liver also show signs of internal spread? Most liver echinococcal cysts tend to have internal metastasis; what makes this patient special? What considerations do the authors have regarding this?\n4. It would be best to provide postoperative imaging findings.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
},
{
"id": "348545",
"date": "30 Dec 2024",
"name": "Yildiray Daduk",
"expertise": [
"Reviewer Expertise Details of diagnostic tests and treatment are incomplete. Specify serological tests",
"imaging findings (ultrasound",
"CT)",
"and treatment rationale",
"including surgical decisions.The discussion lacks depth on the findings' relevance. Emphasize implications for future diagnostic or therapeutic strategies.Provide more clinical details (diagnostic process",
"follow-up outcomes) to enhance utility for practitioners."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDetailed Explanation of the Diagnostic Process\nSerological Tests: While the article mentions that serological tests were conducted, it does not specify which tests were performed (e.g., echinococcal agglutination test, ELISA). Serological positivity is not always expected in Type IV hydatid cysts. Therefore, whether a positive result might have stemmed from another active cyst or a false positive is possible should be discussed. Was the test repeated for control purposes? Ultrasonography Findings: Ultrasonography findings are not included in the report. Details such as the internal structure of the cyst (e.g., septation, wall thickness, calcification) and its relationship with surrounding tissues should be provided. If possible, the ultrasound image should be included. CT Findings:\nThe anatomical features of the cyst (e.g., wall structure, fluid content, septation) should be described. Mediastinal complications (e.g., pericardial effusion, compression of the trachea or major vessels) should be evaluated.\n\nSplenic Calcification: Even if the cyst in the spleen is assumed to be inactive, this suggests potential hydatid disease involvement in other areas of the body. Further diagnostic methods (e.g., whole-body CT/MRI scans) should be employed to investigate cysts in other organs, and the results should be reported. If these were not performed, the rationale should be explained. Hiatus and Gastroscopy: The article states that the cyst extended into the mediastinum via Larrey's hiatus. It should be clarified whether methods like gastroscopy were employed to anatomically assess the hiatus opening. If not, the reasoning should be provided. Figure Descriptions: Figure descriptions are insufficient.\n\nSurgical Method and Rationale\nRationale for Surgical Intervention: It is generally known that Type IV hydatid cysts do not typically require surgery. However, surgical intervention was chosen in this case. The rationale behind this decision (e.g., risk of complications from mediastinal extension or compression on surrounding structures) should be discussed in detail. Minimally Invasive Methods: The article should explain why minimally invasive methods, such as laparoscopy or PAIR, were not considered. Were these methods deemed unsuitable for the patient? Hiatus Intervention: It is not mentioned whether Larrey’s hiatus was addressed during surgery. If no intervention was made, the reasoning should be provided.\n\nSurgical Technique Details\nUse of Scolicidal Solution: The timing, method, and type of scolicidal solution used should be explained, as this is critical for treatment efficacy and complication prevention. Bile Fistula Risk: For cysts larger than 10 cm, the risk of bile fistula increases. It should be clarified whether intraoperative tests (e.g., dye tests for bile ducts) were conducted. Removal of Germinal Membranes: The article should explain how it was ensured that all germinal membranes within the thoracic cyst were completely removed, as this is vital for treatment success and preventing recurrence.\n\nPostoperative Management\nAlbendazole Therapy: Type IV hydatid cysts are generally considered inactive, and postoperative albendazole therapy is not typically required. However, a six-month treatment was administered in this case. The rationale (e.g., microscopic residues or risk of recurrence) should be clearly explained. Follow-Up Process: The long-term follow-up method for the patient should be detailed.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1484
|
https://f1000research.com/articles/13-1483/v1
|
05 Dec 24
|
{
"type": "Correspondence",
"title": "Comment regarding “Positive SARS-CoV-2 RT-qPCR of a nasal swab spot after 30 days of conservation on filter paper at room temperature”",
"authors": [
"Gernot Kriegshäuser"
],
"abstract": "The diagnostic and therapeutic approaches towards the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were a global challenge, and the reverse transcription polymerase chain reaction of virus RNA isolated from nasopharyngeal swabs has become a common tool to confirm the clinical diagnosis of coronavirus disease 2019. Available evidence suggests, that Whatman™ Flinders Technology Associates™ (FTA) cards are a reliable option for the safe transport and storage of viral RNA pathogens. In 2021 FTA cards were shown to be suitable for the stable preservation of SARS-CoV-2 RNA derived from nasopharyngeal swabs even at elevated storage temperatures. Subsequently, another study identified Whatman filter paper to be a cheaper alternative with respect to the stable storage SARS-CoV-2 RNA at room temperature. This correspondence is meant to discuss the performance of both FTA cards and filter paper also scrutinizing performance calculations and respective evaluations.",
"keywords": [
"Filter paper",
"FTA card",
"SARS-CoV-2",
"RNA",
"storage"
],
"content": "\n\nI have read with great interest the article “Positive SARS-CoV-2 RT-qPCR of a nasal swab spot after 30 days of conservation on filter paper at room temperature” by Durand et al.1 The authors present data on the stability of SARS-CoV-2 RNA obtained from nasal swabs and commercially available freeze-dried virus samples spotted and stored on filter paper (Whatman 3M; Schleicher & Schuell). In one experiment, the authors showed, that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive nasal sample immobilized on filter paper and kept for 30 days at room temperature (RT) could successfully be amplified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In another experiment it was demonstrated, that serial dilutions of SARS-CoV-2 RNA derived from strains Omicron and Delta were detectable by RT-qPCR after storage of 30 days at RT at a 50% tissue culture infectious dose (TCID50) of 0.04 and 0.4, respectively. Of note, the filter paper seems to convey some virus inactivation properties because the authors failed to isolate virus obtained from a dried spot after 20 days of tissue culture.\n\nAvailable evidence suggests, that Whatman™ Flinders Technology Associates™ (FTA) cards are a reliable option for safe transport and storage of viral RNA pathogens.2 Minimal storage space, easy transportation, long-term storage at room temperature (RT), and simple extraction protocols are the main advantages of this non-infectious medium. Especially in endemic and developing countries, sample transportation at ambient temperature without the need of cold chain may be of advantage.\n\nIn 2021 and 2022, FTA cards (WhatmanTM FTATM Classic Card, GE Healthcare, Little Chalfont, United Kingdom) were shown to be suitable for the stable preservation of SARS-CoV-2 RNA derived from nasopharyngeal swabs (NPS) even at elevated storage temperatures.3,4 In more detail, we investigated the stability of SARS-CoV-2 RNA in 19 FTA card spot-prep samples stored at 4 different temperatures (-20°C, 4-8°C, RT, 37°C) for 1-3 weeks. After week 3, we observed differences between the Ct values obtained for storage temperatures at -20°C, 4-8°C, RT, and 37°C and a reference FTA card sample (i.e., RNA was extracted immediately after the filter paper had dried out) to range from -0.6 to 1.1%, -2.5 to 4.9%, -1.8 to 4.9%, and 0.6 to 6.4%, respectively.3\n\nIn a first experiment, Durand et al.1 were able to amplify filter-bound SARS-CoV-2 RNA obtained from a nasal sample after storage of 10, 20, and 30 days at RT resulting in Ct gaps of 7, 6 and 5 between the extemporaneous sample at T0 and samples taken at T10, T20 and T30, respectively.\n\nIn a subsequent experiment analyzing freeze-dried virus samples, the authors reported a median Ct gap between an extemporaneous sample isolated at day 0 and different virus dilutions spotted and stored for 30 days at RT of 3.7 and 3.5 for the Delta and the Omicron strain, respectively. Between T10 and T30, the Ct gap was 2.5 and 1.3, respectively.1 In contrast and given the presented Ct values for the Delta strain at dilutions representing a TCID50 of 4 and 0.4, we calculate the median Ct gap to be 6.25, corresponding to the difference between the arithmetical mean Ct values of 36 at T30 and 29.75 at T0. Furthermore, based on the Ct values for the Omicron strain at dilutions representing a TCID50 of 4, 0.4, and 0.04, we calculate the median Ct gap to be 4.5 by subtracting the median Ct value of 28.5 at T0 from the median Ct value at of 33 at T30. With this respect, and by subtracting the median Ct value of 31 at T10 from the median Ct value of 33 at T30, the resulting Ct gap is 2. In the absence of more information, it would be interesting to learn how the authors performed their calculations, especially considering the fact, that these calculations seem to overestimate the filter paper’s performance to stably preserve SARS-CoV-2 RNA.\n\nTo better compare the results of our study3 with those presented by Durand et al.,1 we reanalyzed the data set obtained for 19 FTA spot-prep samples stored for one (T7), two (T14) and three (T21) weeks at RT ( Table 1). The median Ct gap between the extemporaneous NPS (T0) samples and the FTA spot-prep samples extracted at T7, T14, and T21 were 2.80, 2.79, and 2.83, respectively, indicating that FTA cards might not be the cheaper (i.e., approximately two euros per FTA card sample vs. 10 to 80 euro cents per filter paper sample, depending on quality grade and diameter) but the better choice with respect to the stable preservation of SARS-CoV-2 RNA on a dry matrix.\n\n* Nasopharyngeal swab.\n\n** Ct value obtained for the extemporaneous NPS sample.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data associated with this article.\n\n\nAcknowledgements\n\nNone\n\n\nReferences\n\nDurand GA, Amouron A, Grard G, et al.: Positive SARS-CoV-2 RT-qPCR of a nasal swab spot after 30 days of conservation on filter paper at room temperature. J. Med. Virol. 2022; 95: 1–3. Publisher Full Text\n\nCardona-Ospina JA, Villalba-Miranda MF, Palechor-Ocampo LA, et al.: A systematic review of FTA™ cards® as a tool for viral RNA preservation in fieldwork: Are they save and effective? Prev. Vet. Med. 2019; 172: 104772. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKriegshäuser G, Enko D, Reçi L, et al.: Stability of SARS-CoV-2 RNA in FTA card spot-prep samples derived from nasopharyngeal swabs. Clin. Chem. Lab. Med. 2021; 59: e351–e353. PubMed Abstract | Publisher Full Text\n\nKanta P, Chhikara K, Mohan L, et al.: Alternate Approach in Storing and Shipment of SARS-CoV-2 RNA Samples with the Use of FTA Cards. Curr. Microbiol. 2022; 79: 396. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "346656",
"date": "11 Dec 2024",
"name": "Ralf Weiskirchen",
"expertise": [
"Reviewer Expertise Clinical chemistry",
"molecular biology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe comment by Kriegshäuser raises important issues regarding the preservation of SARS-CoV-2 RNA on different substrates, specifically comparing Whatman 3M filter paper and Whatman Flinders Technology Associates (FTA) cards as published by Durand and coworkers in 2022 (1).\nThe author highlights discrepancies in the calculated median Ct (cycle threshold) gaps between the reported findings in the study by Durand and colleagues and those reported by the author himself one year before (2). Krieghäuser noticed that the calculations presented in the commented study might overestimate the effectiveness of filter paper in preserving SARS-CoV-2 RNA. This is a critical observation, as accurate quantification of viral RNA stability is essential for reliable diagnostics and epidemiological studies.\nThe reanalysis of data from their own previous study shows consistent Ct values across different time points (T7, T14, T21), suggesting that FTA cards provide more stable preservation compared to filter paper found in the study by Durand and coworkers. The median Ct values indicate that while both methods can preserve RNA, FTA cards may be preferable due to their better performance despite being slightly more expensive.\nOverall, this commentary emphasizes the necessity for transparency in methodology and calculations when assessing the viability of different sample preservation techniques. It also underscores the importance of using reliable materials for viral RNA storage to ensure accurate detection and analysis.\n\nIs the rationale for commenting on the previous publication clearly described? Yes\n\nAre any opinions stated well-argued, clear and cogent? Yes\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Yes\n\nIs the conclusion balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "354772",
"date": "17 Jan 2025",
"name": "Alexander Viloria Winnett",
"expertise": [
"Reviewer Expertise quantitative nucleic acid measurements",
"infectious disease diagnostics",
"molecular biology",
"epidemiology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of Review\nThe Correspondence seeks to compare and discuss RNA stability on Whatman 3M filter paper (evaluated in Durand et al.) versus Whatman™ Flinders Technology Associates™ (FTA) cards (evaluated in this Correspondence and by the Author in previous work). This comparison and discussion is useful, as these two dry matrices may not exhibit equivalent performance for stabilizing RNA.\nThe Correspondence concludes that “FTA cards might ... be the better choice [compared to Whatman 3M filter paper] with respect to the stable preservation of SARS-CoV-2 RNA on a dry matrix.” However, issues in methodology and clarity of the evaluations in this Correspondence and the study evaluating RNA stability on Whatman 3M filter paper limit the ability to make a balanced and justified conclusion.\nQualitative result of detection of SARS-CoV-2 RNA could be used to compare the two dry matrices. Data from Table 1 in this Correspondence shows that 19 of 19 samples were detectable after 21 days on FTA cards at room temperature. In comparison, Durand et al. report that after 30 days on Whatman 3M filter paper at room temperature, 6 of 10 samples were detectable. While this might appear that FTA cards result in better preservation of RNA, it is important to note first that the time lengths (21 days versus 30 days) are not equivalent, and second that the starting concentrations of target RNA are not equivalent. The Ct value at T0 was below 25 for 74% (14 of 19) samples stored on FTA cards at room temperature for 21 days, but only 20% (2 of 10) samples (originating from 3 clinical specimens) stored at room temperature for 30 days. The lower rate of detection for samples stored on filter paper is likely impacted by lower starting RNA amounts than samples stored on FTA cards. Third, RNA stability on the dry matrix may also be sample dependent, and different samples were used between the evaluations.\nQuantitative result of SARS-CoV-2 RNA amount after storage could be used to compare the two dry matrices. Ct values for a SARS-CoV-2 RNA target in 19 samples stored on FTA cards at room temperature for 21 days were a median of 2.56 higher than the Ct value for the same sample on day 0, which corresponds to approximately 5.9-fold less target RNA. Among 5 samples with detectable target RNA after 30 days on Whatman 3M filter paper at room temperature, Ct values were a median of 5 Ct higher than on day 0. In comparison, 0 of 19 samples (originating from 2 clinical specimens) stored on FTA cards for 21 days exhibited 5 Ct higher than on day 0. This trend would suggest that RNA is more stable on FTA cards than filter paper, however the filter paper condition is drastically underpowered, the time lengths are different, and different samples were evaluated in each condition.\nFTA cards may be the better choice for stable preservation of SARS-CoV-2 RNA compared to Whatman 3M filter paper, but the data presented is insufficient to make this conclusion. Additional studies (ideally head-to-head studies, with equivalent time lengths, and equivalent samples that span a range of starting target RNA amounts) are needed, as well as appropriate quantitative analysis methods.\n\nMajor Comments: 1. The Article would benefit from a brief description of how the composition/structure of Whatman 3M filter paper and the Whatman FTA cards differ.\n2. “Of note, the filter paper seems to convey some virus inactivation properties because the authors failed to isolate virus obtained from a dried spot after 20 days of tissue culture.”\n\nThe claim that the filter paper contributes to the inactivation of the virus is not well substantiated. Firstly, this conclusion relies on only a single sample. Second, inactivation of enveloped viruses after several days outside of a live host is expected, and believed to be due to the kinetics of drying/dehydration (see French et al. mBio 2023). While the process of drying can be affected by surface material (ie. filter paper), one would need to determine the independent contribution of the surface material to viral inactivation to substantiated this claim. The article referenced (from which the data on recovery of infectious virus from a single sample stored on filter paper originates) does not make the claim that filter paper contributed to viral inactivation, and does not compare sample storage on different materials. I encourage the Author of this Correspondence to provide substantiating evidence, or revise this statement.\n\n3. “After week 3, we observed differences between the Ct values obtained for storage temperatures at -20°C, 4-8°C, RT, and 37°C and a reference FTA card sample (i.e., RNA was extracted immediately after the filter paper had dried out) to range from -0.6 to 1.1%, -2.5 to 4.9%, -1.8 to 4.9%, and 0.6 to 6.4%, respectively.”\nRelative differences in Ct values are challenging to interpret and compare, because the magnitude of the relative difference depends on the absolute Ct values. For example, imagine that half the RNA in a sample degrades after 10 days, and that this rate of degradation is not dependent on the amount of starting RNA. If the material started at a Ct of 10, we could expect a Ct of 11 after 10 days: this is an absolute difference of 1 Ct, and a relative difference of 10% (1/10). If the material started at a Ct of 15, we could expect a Ct of 16 after 10 days: this is an absolute difference of 1 Ct, but a relative difference of 7% (1/15). If the material started at a Ct of 25, we could expect a Ct of 26 after 10 days: absolute difference of 1 Ct, but a relative difference of 4% (1/25). If the material started at a Ct of 35, we could expect – theoretically - a Ct of 36 after 10 days: absolute difference of 1 Ct, but relative difference of approximately 3% (1/35). Equivalent fold-changes in material result in lower relative differences of Ct values at higher starting Ct values. Variance metrics for relative difference in Ct (e.g. range) do not reflect variation in degradation among samples.\n\nI encourage the Author to use a clearer and more interpretable summary metric to substantiate this claim. Absolute differences in Ct values (ΔCt) would be a more interpretable summary metric for readers than relative differences. Or, explain why relative difference in Ct values is superior and provide the equation used to calculate relative difference in Ct values.\n4. “FTA cards ... were shown to be suitable for the stable preservation of SARS-CoV-2 RNA derived from nasopharyngeal swabs (NPS) even at elevated storage temperatures”\nPlease also clarify how “stable preservation” is defined in the context of this statement. Data in Table 1, 15% (3 of 19) of the samples presented in Table 1 exhibited an absolute difference of Ct values greater than 3.3 (approximately 10-fold loss of RNA) between T0 and T21.\n\n5. “In a first experiment, Durand et al.1 were able to amplify filter-bound SARS-CoV-2 RNA obtained from a nasal sample after storage of 10, 20, and 30 days at RT resulting in Ct gaps of 7, 6 and 5 between the extemporaneous sample at T0 and samples taken at T10, T20 and T30, respectively.”\nThis statement re-reports a result from Durand et al., without offering additional perspective. I encourage the Author to add an original interpretation to put this result in context, or remove.\nHowever, the Ct gaps reported in this statement, while correctly reproduced from Durand et al., do not make scientific sense. (Perhaps this was what the Author sought to call attention to?) I investigated the underlying statement, and see that Durand et al. report a Ct of 21 at T0, Ct of 28 at T10, Ct of 27 at T20, and a Ct of 26 at T30. It is extraordinary that more RNA (lower Ct) would be measured from the same sample over time, since RNA is expected to degrade over time, resulting in higher Ct values. Indeed, in the second experiment reported in Durand et al. Table 1, Ct values increase over time, for all dilution conditions, as expected.\nI believe data from Durand et al.’s first experiment was erroneously reported, and reproducing the error in this Correspondence should be avoided. The values reported in the main text of Durand et al. do not match underlying data shown in Durand et al. Supplementary Figure 1. At T0 (Durand et al. Fig S1A), sample fluorescence appears to rise above the RFU threshold at a Ct of approximately 21.5. The main text reports a Ct of 21 for this timepoint. At T10 (Durand et al. Fig S1B) I would interpret the Ct as 26, while they report a Ct of 28. At T20 (Durand et al. Fig S1C) I would interpret the Ct as 26, while they report a Ct of 27. Finally at T30 (Durand et al. Fig S1D) I would interpret the Ct as 26, and they report a Ct of 26. It is reasonably expected that initial degradation of RNA would occur between T0 and T10 (from 21.5 to 26), followed by stable Ct values for the sample over time (26). I believe an error was made by Durand et al. when reporting these Ct values in the main text of their manuscript.\n\nIt is critical to avoid propagating this error. I encourage the Author to review and independently interpret the underlying data from Durand et al. Supplementary Figure 1. If the Author believes the measured Ct values to truly be 21, 28, 27, and 26 for T0, T10, T20, and T30 as reported, the Author should explain how this could be physically possible (e.g. greater liberation of RNA from the filter than degradation over time, variability in sample loading or measurement between timepoints) and how these possible explanations impact the conclusions that can be made from the data available.\n6. “In a subsequent experiment analyzing freeze-dried virus samples, the authors reported a median Ct gap between an extemporaneous sample isolated at day 0 and different virus dilutions spotted and stored for 30 days at RT of 3.7 and 3.5 for the Delta and the Omicron strain, respectively. Between T10 and T30, the Ct gap was 2.5 and 1.3, respectively. In contrast and given the presented Ct values for the Delta strain at dilutions representing a TCID50 of 4 and 0.4, we calculate the median Ct gap to be 6.25, corresponding to the difference between the arithmetical mean Ct values of 36 at T30 and 29.75 at T0. ... In the absence of more information, it would be interesting to learn how the authors performed their calculations, especially considering the fact, that these calculations seem to overestimate the filter paper’s performance to stably preserve SARS-CoV-2 RNA.”\nI agree that it is unclear in Durand et al. how the median values reported were calculated, and appreciate the Author of this Correspondence raising this point. I have reanalyzed the data in Durand et al. Table 1, and I was able to reproduce the value they report when following an erroneous analysis method: for the Delta strain, it appears that they subset the data to only dilution conditions where data from both T0 and T30 was available (TCID50 of 4 and TCID50 of 0.4). They then calculated the median Ct value of the two T0 measurements (27.5 and 32), and the median value of the two T30 measurements (35 and 37). They then took the difference between the median from T30 and the median from T0 to get a Ct gap of 3.75.\nI agree with the Author of the Correspondence that this approach is inappropriate. Measurements of Ct value at T0 and Ct value at T30 for a sample are not independent. The method used here neglects the paired nature of the data, and overrepresents the observed stability of RNA on the filter paper.\nIt is more appropriate to calculate the Ct gap (or absolute difference in Ct values, or ΔCt) between T0 and T30 for each sample, and then take the median of the set of Ct gaps, which retains the paired nature of the measurements. The Author of the Correspondence applied this method to obtain a Ct gap of 6.25, which I believe more accurately reflects the effect of time on the amount of RNA measured from the filter paper based on the underlying data than the reported value of 3.75.\nHowever, this is a median of only two observations. These two observations, which are dilutions of a single sample, are insufficient to make quantitative conclusions about the stability of SARS-CoV-2 RNA on filter paper more generally. I would encourage the Author to make the point that this analysis in the referenced study is underpowered.\n7. “Furthermore, based on the Ct values for the Omicron strain at dilutions representing a TCID50 of 4, 0.4, and 0.04, we calculate the median Ct gap to be 4.5 by subtracting the median Ct value of 28.5 at T0 from the median Ct value at of 33 at T30. With this respect, and by subtracting the median Ct value of 31 at T10 from the median Ct value of 33 at T30, the resulting Ct gap is 2.”\nAs discussed in my Comment 6, this method of calculating the median Ct gap is inappropriate, because it neglects the paired nature of T0 and T30 measurements of the same sample. The Author of this Correspondence correctly pointed out the inappropriateness of this mathematical approach in reference to Durand et al., but the critiqued approach was then used by the Author here.\nIf the correct approach (described in Comment 6 above) is applied, the median Ct gap for the Omicron variant observations TCID50 of 4, TCID50 of 0.4, TCID50 of 0.04 between T30 and T0 in Durand et al. Table 1 would be 5.\nHowever, this is a median of only three observations, which are dilutions of a single sample. I would encourage the Author to make the point that this analysis in the referenced study is underpowered.\n8. I am unable to reproduce summary metrics provided in the text of this Correspondence from data in Table 1\nTable 1 provides the measured Ct values for samples stored at room temperature. These data are very helpful. However, I am unable to reproduce the summary metrics listed in the text using data from this table.\nThe range of relative differences in Ct values from T21 to T0 at room temperature is listed in the text as -1.8 to 4.9%. By my calculations from data in Table 1, the range should be 4% to 15%. The value 4% is from Sample 16 in Table 1, which has a T0 Ct of 25.61 and a T21 Ct of 26.75.\n\n(26.75-25.61)/25.61 = 0.04451, or ~4%. The value 15% is from Sample 8 in Table 1, which has a T0 Ct of 24.39 and a T21 Ct of 28.04. (28.04-24.39)/24.39 = 0.14965 or ~15%. If the relative difference in Ct values (and/or other metrics reported in the text) were reported in Table 1 for each sample individually, readers could trace back how the reported values were obtained.\n\nHowever, as described in my Comment 3, I do not recommend reporting relative differences in Ct values. If the Author wishes to report relative differences in Ct values, clarity on how this calculation was performed to get the reported values is requested. Details for how these values were calculated is not provided in the Author's prior work cited.\n\nAdditionally, the median Ct gap (absolute difference in Ct values, or ΔCt) to T0 is listed in the text as 2.80 for T10, 2.79 for T20, and 2.83 for T30. I calculated these values to be 2.37 for T10, 2.61 for T20, and 2.56 for T30. I cannot upload my re-analysis spreadsheet, but am happy to provide upon request.\n\nMinor comments: 1. In Table 1, NPS Sample 1’s Ct at T0 has a “,” while all other data in the Table contain decimal points (“.”).\n2. “The median Ct gap between the extemporaneous NPS (T0) samples and the FTA spot-prep samples extracted at T7, T14, and T21 were 2.80, 2.79, and 2.83, respectively, indicating that FTA cards might not be the cheaper (i.e., approximately two euros per FTA card sample vs. 10 to 80 euro cents per filter paper sample, depending on quality grade and diameter) but the better choice with respect to the stable preservation of SARS-CoV-2 RNA on a dry matrix.”\nConsider breaking this single sentence into multiple sentences for readability.\n\nIs the rationale for commenting on the previous publication clearly described? Yes\n\nAre any opinions stated well-argued, clear and cogent? Partly\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Partly\n\nIs the conclusion balanced and justified on the basis of the presented arguments? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1483
|
https://f1000research.com/articles/13-1478/v1
|
04 Dec 24
|
{
"type": "Genome Note",
"title": "The complete chloroplast genome of a centennial olive tree (Olea europaea, Oleaceae) from the southern Peruvian coast",
"authors": [
"Carla L. Saldaña",
"Luz S. Chura-Llanos",
"Richard Estrada",
"Elizabeth Fernandez",
"Franz Zirena Vilca",
"Juan C. Guerrero-Abad",
"Carlos A. Amasifuen-Guerra",
"Dina L. Gutierrez-Reynoso",
"Pedro Injante",
"Carlos I Arbizu",
"Carla L. Saldaña",
"Luz S. Chura-Llanos",
"Richard Estrada",
"Elizabeth Fernandez",
"Franz Zirena Vilca",
"Juan C. Guerrero-Abad",
"Carlos A. Amasifuen-Guerra",
"Dina L. Gutierrez-Reynoso",
"Pedro Injante"
],
"abstract": "Olive (Olea europaea Linaeus 1753) is one of the valuable fruit trees and very important edible oil plant in the world. The chloroplast (cp) genome of an olive tree (Olea europaea) from the southern Peruvian arid coast was obtained for the first time. Genomic DNA of high quality was used to generate librarieswith Illumina Hiseq paired-end methods. The cp genome is 155,886 pb in length and contains a large single-copy region (LSC) of 86,610 pb and a small single copy region (SSC) of 17,790 pb separated by two inverted repeat (IR) regions (25,741bp). The cp genome of olive contains 124 genes that consists of 80 protein-coding genes, 36 tRNA, eight rRNA. Phylogenetic analysis showed this olive tree is sister to O. europaea subsp. maroccana (Oleeae tribe). This study presents the first overview of the chloroplast genome organization and phylogenetics of O. europaea, offering valuable insights for genetic and evolutionary research in the genus Olea.",
"keywords": [
"plastome",
"NGS",
"coastal zone",
"phylogenomics"
],
"content": "Introduction\n\nThe olive Olea europaea (Oleaceae) is a subtropical tree distributed on most continents in tropical and temperate environments (Dupin et al., 2020). The genus Olea comprises about 40 old world species (Jensen et al., 2002) and the majority of Oleaceae species possess an economic importance as most olive fruits are used for oil extraction. Vegetable oil is important for its nutritional and healthy advantages compared to others (Rallo et al., 2000). Currently, ten olive tree chloroplast (cp) genomes were reported from Mediterranean region (Besnard et al., 2011), Italy, Spain, China (Niu et al., 2020), and Jordan (Haddad et al., 2021). However, to date, the olive tree chloroplast genome from Peru has not been reported. In this study, we sequenced, assembled, and annotated for the first time the complete chloroplast genome of a centennial the olive tree from Peru ( Figure 1), using next generation sequencing (NGS), providing valuable information for genetic and evolutionary studies in the genus Olea.\n\n\nMethods\n\nPlant materials and extraction of genomic DNA Fresh young leaves were collected from “El Algarrobal” district located in the Ilo province from Moquegua region (latitude 17.61294, longitude -71.27136). The specimen (MOQ001169) was deposited at the National University of Moquegua Herbarium (http://www.hmoqueguensis.unam.edu.pe/, Hibert Huaylla-Limachi hmoqueguensis@unam.edu.pe) under the voucher Nro. 001169. DNA was extracted using CTAB method (Doyle and Doyle 1990) with minor modifications for this specie. The quality and the quantity were evaluated on a 1% agarose gel and fluorescence using the Qubit™ 4 Fluorometer (Invitrogen, Waltham, MA, USA), respectively.\n\nDNA sequence and genome assembly Library construction pair-end reads and sequencing were carried out using Illumina HiSeq 2500 platform and a PE 150 library, with the NexteraXT DNA Library Preparation Kit (Illumina, San Diego, CA, USA). We removed the adapters and verified the quality of reads employing Trim Galore (Martin, 2011) with arguments: −F embplant_pt −R 15 –reduce-reads-for-coverage inf. The cp genome was assembled with GetOrganelle v1.7.2 (Jin et al., 2020), using Olea europaea subsp. europaea (NC_015401) as reference. SPAdes v3.11.1 (Bankevich et al., 2012), bowtie2 v2.4.2 (Langmead and Salzberg, 2012), and BLAST+ v2.11 (Camacho et al., 2009) were also used in the pipeline with default settings.\n\nThe cp genome was annotated using GeSeq in CHLOROBOX web service (Tillich et al., 2017) Default settings were applied, and comparisons were made with all available plastid genomes of Oleae in the NCBI database, followed by manual curation\n\nTo understand the phylogenetic position of Olea europaea, a maximum likelihood (ML) tree of 19 genomes retrieved from GenBank was reconstructed. First, we employed MAFFT v.7.475 (Katoh and Standley, 2013) to align those genomes. Then, with a GTR + GAMMA model of evolution, we obtained the best-scoring ML tree, considering 1,000 bootstrap (BS) inferences with RAxML v8.2.11 (Stamatakis, 2014). We employed capirona (Calycophyllum spruceanum) cp genome as an outgroup (OK326865). The aligned data that was employed for the phylogenetic analysis consists of 187,111 bp (Supplemental Data 1, https://doi.org/10.5061/dryad.tmpg4f57q).\n\n\nResults\n\nThe complete chloroplast genome of olive was 155,886 bp in length with typical quadripartite structure that included a large single-copy (LSC) of 86,610 bp and a small single copy region (SSC) of 17,790 bp separated by two inverted repeat (IR) regions (25,741 bp). Following of annotation and subsequent modifications, we submitted the complete chloroplast (cp) genome sequence to the GenBank database. This submission is associated with the accession number: ON767107. The average depth of coverage is 17,673.05X (Supplementary Figure 1, https://doi.org/10.5281/zenodo.14061216). The chloroplast genome contains 124 genes that consisted of 80 protein-coding genes, 36 tRNA, 8 rRNA. Of the total genes reported 12 present one intron. PafI and clpP1 genes contained two introns. We further report that most genes are present as a single copy, except 14 genes that were duplicated in IR regions ( Figure 2). A total of 11 cis-splicing genes (rps16, atpF, rpoC1, pafl, clpP1, petB, petD, rpl16, rpl2, ndhB, ndhA) were identified; one trans-splicing gene (rps12) was also identified (Supplementary Figure 2, Supplementary Figure 3).\n\nGenes belonging to different functional groups are color-coded. The genes functions are indicated colored in the bottom left corner. The dark grey inner circle indicates the presence of nodes in the LSC, SSC, IR regions).\n\nThis study examined 19 species of the Oleaceae family, with one outgroup, Calycophyllum spruceanum (OK326865), to understand their evolutionary relationships by analyzing complete chloroplast genome sequences. Maximum likelihood (ML) analysis revealed three distinct monophyletic groups within the tribes Jasminenae, Oleeae, and Forsythiae, with 17 of the nodes showing 100% bootstrap support. In addition, O. europaea is shown to be sister to O. europaea subsp. Maroccana, and sister to them is O. europaea subsp. cuspidata ( Figure 3). As expected, Olea europaea was categorized in the Oleeae tribe. These phylogenetic trees are consistent with the established classification of the Oleaceae family.\n\n\nDiscussion and conclusions\n\nIn this study, we assembled for the first time the chloroplast genome sequence of the centennial olive tree (Olea europaea) from the southern Peruvian coast. The results differ from other chloroplast genomes of Olea europaea, such as O. europaea subsp. europaea (NC_015401), which presents 85 protein-coding genes, 37 tRNA, and 8 rRNA (Haddad et al., 2021). Niu et al. (2020) reported that two varieties of O. europaea, subsp. europaea var. sylvestris and subsp. cuspidata, presented 133 genes, including 87 protein-coding genes, 37 tRNA, and 9 rRNA. Likewise, they found that the chloroplast genome length for both species were 155,886 bp (Niu et al., 2020). The phylogenetic results showed O. europaea is sister to O. europaea subsp. maroccana and O. europaea subsp. cuspidata in independent sister clade to other species of genus Olea the chloroplast genome sequence and annotation were submitted to NCBI with accession number ON767107.1.\n\nPeruvian olive chloroplast genome will stimulate additional work to develop molecular markers for their application in a genomic selection program of superior individuals in early stages. In addition, this study may be a basis to know the location of genes of interest that may be used in gene editing. This work promotes knowing more about the genetics of the Peruvian olive tree, promoting its modern genetic improvement and conservation.\n\n\nAuthors’ contribution\n\nC.L.S. analyzed the data, was also involved in drafting the article. L.C.-L., C.I.A. and R.E. analyzed the data. E.F.-H., F.Z.-V., J.C.G.-A., C.A.-G., D.L.G.-R. were involved in the conception and design of the work. L.C.-L. and F.Z.-V. were involved in sample collection. F.Z.-V., J.C.G.-A., P.I. and C.I.A. were involved in data interpretation.\n\nF.Z.-V., J.C.G.-A., P.I. and C.I.A. were involved in funding acquisition. C.I.A was involved in drafting the article. All authors read and approved the manuscript.\n\n\nEthical approval\n\nOlive sample collected and employed in this work do not involve protection determined by the Republic of Peru. Consequently, this study was exempted from ethical approval.",
"appendix": "Data availability statement\n\nNCBI: Complete chloroplast genome. Accession number ON767107; https://www.ncbi.nlm.nih.gov/nuccore/ON767107.\n\nDryad: Supplementary material.\n\nThe complete chloroplast genome of a centennial olive tree (Olea europaea, Oleaceae) from the southern Peruvian coast. https://doi.org/10.5061/dryad.tmpg4f57q (Saldaña et al., 2024a).\n\nThis link contains the following extended data:\n\n• Supplementary_Figure_1.jpg\n\n• Supplementary_Figure_2.jpg\n\n• Supplementary_Figure_3.jpg\n\nZenodo: Supplementary material. https://doi.org/10.5281/zenodo.14061216 (Saldaña et al., 2024b).\n\nThis link contains the following extended data:\n\n• Supplementary_Data_1.phy\n\n• README.md\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication) (http://creativecommons.org/publicdomain/zero/1.0/).\n\n\nReferences\n\nBankevich A, Nurk S, Antipov D, et al.: SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 2012; 19: 455–477. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBesnard G, Hernández P, Khadari B, et al.: Genomic profiling of plastid DNA variation in the Mediterranean olive tree. BMC Plant Biol. 2011; 11(1): 12–80. Publisher Full Text\n\nCamacho C, Coulouris G, Avagyan V, et al.: BLAST+: Architecture and applications. BMC Bioinform. 2009; 10: 421. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDoyle J, Doyle J: Isolation of plant DNA from fresh tissue. Focus. 1990; 12(13): 39–40.\n\nDupin J, Raimondeau P, Hong-Wa C, et al.: Resolving the phylogeny of the olive family (Oleaceae): confronting information from organellar and nuclear genomes. Genes. 2020; 11(12): 1508. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHaddad N, Migdadi H, Brake M, et al.: Complete chloroplast genome sequence of historical olive (Olea europaea subsp. europaea) cultivar Mehras, in Jordan. Mitochondrial DNA Part B. 2021; 6(1): 194–195. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJensen SR, Franzyk H, Wallander E: Chemotaxonomy of the Oleaceae: iridoids as taxonomic markers. Phytochemistry. 2002; 60(3): 213–231. PubMed Abstract\n\nJin JJ, Yu WB, Yang JB, et al.: GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes. Genome Biol. 2020; 21(1): 1–31. Publisher Full Text\n\nKatoh K, Standley DM: MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 2013; 30(4): 772–780. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim HW, Lee HL, Lee DK, et al.: Complete plastid genome sequences of Abeliophyllum distichum Nakai (Oleaceae), a Korea endemic genus. Mitochondrial DNA Part B. 2016; 1(1): 596–598. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLangmead B, Salzberg SL: Fast gapped-read alignment with Bowtie 2. Nat. Methods. 2012; 9: 357–359. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee HL, Jansen RK, Chumley TW, et al.: Gene relocations within chloroplast genomes of Jasminum and Menodora (Oleaceae) are due to multiple, overlapping inversions. Mol. Biol. Evol. 2007; 24(5): 1161–1180. PubMed Abstract | Publisher Full Text\n\nMartin M: Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. Journal. 2011; 17(1): 10–12. Publisher Full Text\n\nNiu E, Jiang C, Wang W, et al.: Chloroplast Genome Variation and Evolutionary Analysis of Olea europaea L. Genes. 2020; 11(8): 879. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlofsson JK, Cantera I, Van de Paer C, et al.: Phylogenomics using low-depth whole genome sequencing: A case study with the olive tribe. Mol. Ecol. Resour. 2019; 19(4): 877–892. PubMed Abstract | Publisher Full Text\n\nPark J, Min J, Kim Y, et al.: The complete chloroplast genome of a new candidate cultivar, Dae Ryun, of Abeliophyllum distichum Nakai (Oleaceae). Mitochondrial DNA Part B. 2019; 4(2): 3713–3715. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaldaña CL, Rodriguez-Grados P, Chávez-Galarza JC, et al.: Unlocking the complete chloroplast genome of a native tree species from the Amazon Basin, capirona (Calycophyllum spruceanum, Rubiaceae), and its comparative analysis with other Ixoroideae species. Genes. 2022; 13(1): 113. Publisher Full Text Publisher Full Text\n\nSaldaña C, Chura-Llano L, Estrada R, et al.: Supplementary data of chloroplast genome of a centennial olive tree from the Peruvian coast. [Dataset]. Dryad. 2024a. Publisher Full Text\n\nSaldaña C, Chura-Llano L, Estrada R, et al.: Supplementary data of chloroplast genome of a centennial olive tree from the Peruvian coast. Zenodo. 2024b. Publisher Full Text\n\nRallo P, Dorado G, Martin A: Development of simple sequence repeats (SSRs) in olive tree (Olea europaea L.). Theor. Appl. Genet. 2000; 101(5): 984–989. Publisher Full Text\n\nStamatakis A: RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014; 30(9): 1312–1313. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTillich M, Lehwark P, Pellizzer T, et al.: GeSeq–versatile and accurate annotation of organelle genomes. Nucleic Acids Res. 2017; 45(W1): W6–W11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan de Paer C, Bouchez O, Besnard G: Prospects on the evolutionary mitogenomics of plants: a case study on the olive family (Oleaceae). Mol. Ecol. Res. 2018; 18: 407–423. PubMed Abstract | Publisher Full Text\n\nWang X, Cai F, Zhang C, et al.: Characterization of the complete chloroplast genome of the ornamental plant Osmanthus cooperi. Mitochondrial DNA Part B. 2019; 4(2): 2314–2315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhu X, Xiong Z, Yang K, et al.: The complete chloroplast genome of Myxopyrum hainanense and phylogenic analysis of Oleaceae. Mitochondrial DNA Part B. 2020; 5(3): 2103–2104. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "357668",
"date": "23 Jan 2025",
"name": "Jun Kim",
"expertise": [
"Reviewer Expertise Genome assembly using long-read sequencin"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this manuscript, which reports the chloroplast genome of a centennial olive tree. It is commendable that the authors have submitted their data to the NCBI database, making it freely accessible to other researchers. With recent advancements in long-read sequencing technologies, it is now possible to assemble entire genomes, not just chloroplast genomes. I look forward to the potential publication of a complete genome assembly of this species in the future. I have noted a few minor issues in the manuscript. For future submissions, I strongly recommend that the authors utilize a proofreading or editing platform. Specific points are as follows:\n[Abstract] Genomic DNA of high quality was used to generate librarieswith --> libraries with\n\na large single-copy region (LSC) of 86,610 pb and a small single copy region (SSC) --> single-copy region (SSC)\n155,886 pb --> bp 17,790 pb --> bp\n[Introduction] In this study, we sequenced, assembled, and annotated for the first time the complete chloroplast genome of a centennial the olive tree from Peru ( Figure 1) --> (Figure 1)\n[Methods] Plant materials and extraction of genomic DNA Fresh young leaves were collected --> \"Plant materials and extraction of genomic DNA\" should be bold and should include a “\\n” at the end to break up an awkwardly joined sentence.\nwith minor modifications for this specie --> species\nDNA sequence and genome assembly Library construction --> \"DNA sequence and genome assembly\" should be bold and should include a “\\n” at the end to break up an awkwardly joined sentence.\n−F embplant_pt −R 15 –reduce-reads-for-coverage inf --> The en dash (\"−\") might be \"--\"\nThe cp genome was annotated using GeSeq in CHLOROBOX web service (Tillich et al., 2017) Default settings were applied, and comparisons were made with all available plastid genomes of Oleae in the NCBI database, followed by manual curation --> These sentences sentences need to end with a period (\".\").\n[Results] To understand the phylogenetic position of Olea europaea, a maximum likelihood (ML) tree of 19 genomes retrieved from GenBank was reconstructed. --> When referring to “19 genomes,” please specify the taxon (likely the Oleaceae family). Additionally, the relevant accession numbers shown in Figure 3 should be also mentioned in this sentence.\nThe average depth of coverage is 17,673.05X --> Please replace \"X\" with the multiplication symbol \"×\" where appropriate.\nIn addition, O. europaea is shown to be sister to O. europaea subsp. Maroccana, and sister to them is O. europaea subsp. cuspidata ( Figure 3) --> (Figure 3)\n\nAre the rationale for sequencing the genome and the species significance clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Yes",
"responses": []
},
{
"id": "357674",
"date": "28 Jan 2025",
"name": "Rajagopal Kammara",
"expertise": [
"Reviewer Expertise Genomics",
"Proteomics and bacteriocins",
"smart probiotics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe major objective is understanding the genomics of Olea europaea chloroplast genome. It is novel, and not yet reported from Peru. Thorough discussion at genome level emphasizing the secondary metabolite pathways etc., is not discussed it requires more emphasis. It is well documented that the value of this tree is tremendous by showing uniqueness at genome level may bring more readership and very useful globally. Therefore, the above said needs to be discussed further.\nModifications required 1. Genomic DNA of high quality was used to generate libraries with Illumina Hiseq paired-end methods 2.The cp genome of olive contains 124 genes that consists of 80 protein-coding genes, 36 tRNA, eight rRNA 36 tRNA, eight rRNA ended as it is an incomplete sentence. 3. Following of annotation and subsequent modifications, we submitted the complete chloroplast (cp) genome sequence to the GenBank database. 4. Of the total genes reported 12 present one intron 5. Figure 2. Schematic map of features of Olea europaea chloroplast genome (Genes drawn outside the outer Needs to fill the gaps….\n\nIncomplete Gaps need to be filled in the MS\nA briefing of the Genomic DNA extraction procedure is required as it is the backbone of the manuscript The presence of Secondary metabolite pathways needs to be emphasized The emphasis at the genome level to show that the Peruvian Olea europaea tree is unique\n\nAre the rationale for sequencing the genome and the species significance clearly described? Partly\n\nAre the protocols appropriate and is the work technically sound? Partly\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1478
|
https://f1000research.com/articles/13-815/v1
|
19 Jul 24
|
{
"type": "Research Article",
"title": "Factors Influencing Climate-Smart Agriculture Practices Adoption and Crop Productivity among Smallholder Farmers in Nyimba District, Zambia",
"authors": [
"Chavula Petros",
"Samuel Feyissa",
"Million Sileshi",
"Chizumba Shepande",
"Samuel Feyissa",
"Million Sileshi",
"Chizumba Shepande"
],
"abstract": "Background The profound impacts of climate change on the environment, economy, and society are anticipated to significantly influence smallholder farmers, whose livelihoods and traditional ways of life are inextricably intertwined with the natural environment. This comprehensive study delves into the multifaceted factors shaping the adoption of climate-smart agricultural practices and their subsequent effects on crop productivity among the small-scale farming communities in Nyimba District, situated within Zambia.\n\nMethods The study collected data from 194 smallholder farmer households across 12 villages in 4 agricultural camps of Nyimba District between June and July 2022. A logistic regression model was utilized to assess the factors influencing crop production and the adoption of climate-smart agricultural practices in response to climate change and variability within the study area. Furthermore, propensity score matching was performed to evaluate the impacts of adopting climate-smart agriculture by comparing adopter households with their non-adopter counterparts.\n\nResults The logit regression model’s findings from the research indicate that several factors influence smallholder farmer households’ adoption of climate-smart agricultural techniques and crop productivity. These factors include the farmer’s educational level, household size, fertilizer utilization, the household head’s age and gender, farming experience duration, livestock ownership status, annual household income, farmland size, the household head’s marital status, and access to climate-related information. Additionally, the propensity score matching analysis revealed that crop yields among smallholder farmers who adopted climate-smart agricultural practices were 20.20% higher compared to non-adopters. Furthermore, the analysis showed that implementing such practices in the study area led to a 21.50% increase in maize yields for adopter households relative to their non-adopter counterparts.\n\nConclusion The findings of this research offer valuable insights to policymakers, guiding them in enhancing farmers’ climate change adaptation strategies and formulating relevant policies. Nevertheless, these initiatives and concerted efforts possess the potential to mitigate the detrimental impacts posed by climate change and climatic variability. This manuscript is an extract from my master of science degree in climate-smart agriculture from Haramaya University titled ‘Climate-Smart Practices: Effects of Agroforestry and Conservation Agriculture on Selected Physicochemical Properties of Soils and Crop Productivity among Smallholder Farmers, in Nyimba, Zambia.’ Please refer to this link; http://ir.haramaya.edu.et/hru/bitstream/handle/123456789/6402/PETROS%20CHAVULA.pdf?isAllowed=y&sequence=1",
"keywords": [
"Adoption",
"Agriculture production",
"Climate-smart agriculture",
"Climate change",
"Crop productivity"
],
"content": "1. Introduction\n\nClimate change is already hindering the growth of agricultural production, both livestock and crop farming, on a global scale (Alfani et al., 2019). Greater climate variability and shifts in climatic patterns exacerbate production risks and strain farmers’ ability to cope. These climatic changes pose threats to accessing nutritious food for urban, peri-urban, and rural communities due to decreased agricultural output and reduced household income (Ivanova et al., 2020; Sharifi, 2021; Mossie, 2022), as well as increased risks that disrupt food markets. The 2018 assessment from the Intergovernmental Panel on Climate Change (IPCC) states that food output is impacted by climate change in most parts of the world, with negative consequences predominating over positive ones. Developing nations are particularly vulnerable to additional negative effects. In many parts of the world, there has already been and is predicted to be an acceleration of increases in the frequency and intensity of severe events, such as drought, flooding, heavy rainfall, and high maximum temperatures (Murray & Ebi, 2012; IPCC, 2018). It is anticipated that average and seasonal maximum temperatures will keep rising along with an overall increase in average rainfall. But the distribution of these effects won’t be uniform. By the end of the twenty-first century, there will probably be more drought and scarcity of water in existing arid areas.\n\nClimate change is projected to contribute to and/or is already causing a global reduction in cereal yields, such as maize and wheat declining by 3.8% and 5.5% respectively. Several researchers warn that crop productivity will experience steep declines when temperatures exceed critical physiological thresholds for these crops. Smallholder farmers, including poor producers, the landless, and marginalized ethnic groups, are among the most vulnerable to the impacts of climate change (CIAT & World Bank, 2017; Makate, 2019). Their livelihoods and food security are threatened by the reduced agricultural yields and disruptions to food systems caused by climate change. Climate change-induced extreme weather events and shocks can have long-lasting impacts by altering investment incentives, increasing the likelihood of low-risk, low-return ventures, and decreasing the chances of successful agricultural advancements. According to studies, the average yields of Zambia’s major crops, such as wheat, sorghum, and maize, are likely to be significantly affected by climate change, as the agronomic conditions for these crops may deteriorate across a significant portion of the country (Molieleng et al., 2021; Chavula, 2022; Stahlbaumer et al., 2022).\n\nClimate change-induced extreme events and shocks, such as droughts and floods, have a significant impact on crop production in Zambia and other Sub-Saharan African countries. However, due to the intricate nature of agricultural systems in Sub-Saharan Africa and their interrelation with the socio-economic aspects of smallholder farmers’ households, an integrated approach has been promoted to maximize productivity at the smallholder agricultural landscape and adapt to climate change. These approaches and interventions are termed ‘climate-smart agriculture (CSA)’ (Makate, 2019; Odubote & Ajayi, 2020; Zakaria et al., 2020; Molieleng et al., 2021).\n\nThe integrated approach recognizes the complexity of agricultural systems in Sub-Saharan Africa and their interconnectedness with the socio-economic factors affecting smallholder farmers’ households (Beedy et al., 2010). Due to adopting climate-smart agricultural practices, smallholder farmers can enhance productivity while simultaneously adapting to the impacts of climate change on their agricultural landscapes.\n\nIn Zambia, as farmers grappled with mounting economic pressures, environmental degradation, and climatic adversities towards the close of the 20th century, they turned to climate-smart agriculture (CSA) as a viable solution. The initial thrust of CSA practices was to enable smallholder farmers to sustain viable production levels, thereby securing their role as active participants in the agricultural landscape. The emergence of CSA was driven by the need to mitigate the deleterious impacts of climate change on smallholder farming communities. To bolster household resilience against climatic variability and rehabilitate degraded lands, the Zambian government has been spearheading efforts to promote the widespread adoption of CSA (Ngoma et al., 2021). These endeavors have been facilitated through collaborations with regional, national, and global research and development institutions (Ngoma et al., 2021). CSA encompasses a suite of practices, including conservation agriculture, integrated pest management, organic farming methodologies, sustainable agricultural techniques, integrated nutrient management, multi-cropping systems, and agroforestry approaches. The overarching objectives of these practices are to augment household incomes, enhance agricultural productivity, and cultivate climate resilience through judicious fertilizer application and sustainable land stewardship (Newell et al., 2019).\n\nGiven the significance of climate-smart agriculture (CSA), the Zambian government has prioritized promoting climate-smart farming practices, such as organic farming, integrated pest management, agroforestry, conservation agriculture, and integrated agricultural practices, among others. These practices have become crucial components of extension and rural advisory service delivery. However, unlike previous empirical studies, this research investigates the factors influencing the adoption of climate-smart farming practices and their impact on crop production among smallholder farmers in Nyimba district, Zambia. This study deviates from earlier research by specifically examining the drivers behind the adoption of climate-smart agricultural techniques and their effects on crop yields among smallholder farmers in Nyimba district. By understanding these influences, policymakers and agricultural extension services can better tailor their efforts to facilitate the widespread adoption of CSA practices, ultimately enhancing the resilience and productivity of smallholder farming systems in the face of climate change.\n\nIn the face of changing climatic conditions and climate change, climate-smart agriculture (CSA) is an approach to transform and reorient agricultural systems to ensure food security (Chavula, 2021). Climate change disrupts food markets, putting food supply and production at risk. Strengthening farmers’ adaptive capacity and enhancing the mitigation potential and efficiency of agricultural production systems can mitigate these risks. Smallholder farmers who are aware of climate change or perceive it as a reality are more likely to adopt climate-smart agricultural practices. These farmers aim to achieve the three pillars of CSA: improving household income and productivity, enhancing resilience and adaptation, and reducing greenhouse gas emissions. The adoption of climate-smart agriculture to attain these principles is influenced by institutional, cognitive, and socioeconomic factors (Figure 1).\n\n\n2. Methods\n\n2.1.1 Location\n\nThe research was carried out in Nyimba district of Eastern Province Zambia. The district is situated 334 kilometers East of Lusaka Zambia’s national capital. In the South the district borders with Mozambique, North with Muchinga province, West with Lusaka province, and East with Petauke district. The district lies between latitude (13°30′1019″ and 14°55′81426″ South) and longitude (30° 48′5047″ and 31°48′20252′′East) (Figure 2).\n\n2.1.2 Climate, soil and topography\n\nZambia is divided into three agro-ecological zones: Zone I, Zone II (subdivided into IIa and IIb), and Zone III. Nyimba district falls within Zone I, which covers the Southern and Eastern rift valleys of the Zambezi and Luangwa River basins. This zone also extends to parts of the Western and Southern provinces in the south of Zambia. The average annual rainfall in Nyimba district ranges from 600 to 900 mm, with the wettest months being December to February and a distinct dry season from May to November. The annual mean temperature is 24.2°C, while the daily temperature range is from 10.3°C to 36.5°C (Figure 3). Topographically, the district comprises hills and plateaus, with soils characterized as Lithosol-Cambisols, while in the valleys, the soils are classified as Fluvisol-Vertisols. The elevation varies from 450-1000 m at the bottom of the Luangwa River valley, extending to the plateau near the Nyimba district center and reaching even higher altitudes on the mountain tops in the western part of the district.\n\n2.1.3 Vegetation type\n\nThe Miombo woodland is the most dominant formation and habitat type in Southern Africa (Gumbo and Dumas-Johansen, 2021; Montfort et al., 2021). Miombo woodland is also the major forest type in Zambia itself, covering approximately 45% of the entire land surface (Kalinda, 2008). Nyimba is located in the middle of the Miombo Ecoregion, a biome with a variety of flora types that is dominated by tree species from the Caesalpinioiae subfamily of leguminous plants (Timberlake et al., 2010). Depending on the climate, soil, landscape position, and degree of disturbance, the ecoregion’s vegetation varies in composition and structure (Timberlake et al., 2010; Halperin et al., 2016). Nyimba is located in the arid ecozone and is characterised by four types of plants: Dry miombo woodland (i.e., Brachystegia spiciformis, Brachystegia boehmii and Julbernardia globiflora), Mopane woodland (i.e., Colophospermum mopane), Munga woodland (i.e., Vechellia sp., Senegalia sp., Combretum sp., and trees associated with the Papilionoideae subfamily) and Riparian Forest (i.e., mixed tree species).\n\n2.1.4 Land use and farming systems\n\nNyimba district total land area is about 10,500 square-kilometers according to population and housing census of 2010. Therefore, 82% of the district population is agrarian with average household income. These households are farmers who are into mixed agriculture practices dominating the agricultural scene in the district. However, local smallholder farmers in the district practice some sort of shifting cultivation. Under this agricultural system, crops are grown in mounds and/or ridges in most cases maize. The major crops grown in include banana (Musa sp.), maize (Zea mays), finger millet (Eleusine coracana), groundnuts (Arachis hypogaea), haricot bean (Phaseolus vulgaris), cowpeas (Vigna unguiculata spp.) and soybean (Glycine max). Multiple cropping system is common among the farming households were cultivated land is on gently and moderately on steep slopes. The topography of the land in the district makes the agricultural or cultivation pattern different from other areas. Therein, cropping system is alongside livestock production such as cattle, goat, chickens, ducks and doves. Besides agricultural activities, farmers are engaged in charcoal production, timber, firewood supply and non-timber forest products (NTFPs) from the miombo woodland for household economic gain (Policy Brief, 2016).\n\nPrior to the actual data collection, an exploratory study was conducted to gather essential information about the research area. The information gathered included the following: the distance between villages, the number of farming households per village, contact details for lead farmers, households adopting climate-smart agricultural (CSA) practices, the location of croplands, and the identification of central meeting points for focus group discussions (FGDs).\n\n2.2.1 Sampling technique\n\nThis study utilized a multi-stage random sampling approach to recruit participants from smallholder farming communities in Zambia. These farming communities, known as agricultural camps, are designated by the Ministry of Agriculture of the Republic of Zambia. The camps group smallholder farmers’ residences within a district, facilitating easy access to agricultural extension services. From the eight agricultural camps in Nyimba District, four camps – Ndake, Central Camp, Lwende, and Ofumaya – were randomly selected for the study. These four camps collectively house 10,700 farmers. To determine an appropriate sample size, the study employed Slovin’s formula. Additionally, three villages from the four selected camps were randomly chosen for data collection. These villages were Sikwenda, Sichipale, Mawanda, Elina, Katumbila, Sichalika, Malalo, Mwenecisango, Mulivi, Lengwe, Mofu, and Yona. With a margin of error set at 0.05, the initial calculated sample size was 386 participants. However, to optimize resources, the researchers increased the margin of error to 0.1, resulting in a smaller sample size of 99 participants. Achieving this reduced sample size required additional time and financial investments, but it was a trade-off deemed necessary for the successful completion of the study.\n\nSample size formula: Slovin’s (1960) formula.\n\nUltimately, the researchers opted for a compromise, settling on a sample size of 194 participants, which fell between the initial calculations of 99 (with a 0.1 margin of error) and 386 (with a 0.05 margin of error). With the assistance of agricultural camp officers, farmer registers from each selected village were utilized to randomly identify potential participants using an Excel spreadsheet.\n\n2.2.2 Focus group discussion\n\nIn-depth information regarding the factors influencing the adoption of climate-smart agricultural practices, crop productivity, perceptions of these practices, the use of CSAPs, and perspectives of climate change was gathered through focused group discussions (FGD). An open-ended FGD study tool that was designed was used to achieve this. Due to the fact that delicate topics are revealed during the execution, focus groups are thought to be superior than one-on-one interviews. Individual farmers frequently find it difficult to completely express themselves in one-on-one interviews. Four (4) focus group discussions (FGDs) involving village headmen, women, men, and youth were conducted within the study region. The FGD meetings were arranged in convenient locations for individual farmers to attend. FGDs were mostly used to augment data that was gathered through household questionnaires.\n\n2.3.3 Household interviews\n\nThere were both closed-ended and open-ended questions on the survey. The questionnaire was pre-tested six times for appropriateness (e.g., clarity, adequacy, and question sequence) prior to conducting the household interviews. The questionnaire was then modified based on the results. The questions were pre-tested on smallholder farmers’ homes who did not take part in the study.\n\nFor data collection, the study employed three enumerators who underwent training and supervision from the principal researcher, an experienced professional in the field. The enumerators meticulously verified and corrected the gathered data after each day of fieldwork. Subsequently, the validated information was securely backed up on the CSPRO Cloud platform (https://www.csprousers.org/help/CSDeploy/deployment_options.html).\n\nOutcome variables\n\nThe outcome variable for this study is the impact of adopting climate-smart agriculture practices on crop productivity among smallholder farmers’ households. Additionally, the study examines the factors influencing both crop productivity and the adoption of climate-smart agriculture practices (CSAPs) among smallholder farmers in the Nyimba district.\n\nDependent variables\n\nSmallholder farmers’ household decision to adopt CSAPs\n\nThe dependent variable was whether a smallholder farmer’s household adopted Climate-Smart Agricultural Practices (CSAPs) or not, taking a value of 1 if the household adopted CSAPs and 0 if it did not. The main objective was to identify the factors influencing the adoption of CSAPs among smallholder farmers’ households in the Nyimba district of Zambia.\n\nTo evaluate the impact of Climate-Smart Agricultural Practices (CSAPs) on crop productivity, this study employed the Propensity Score Matching (PSM) method, comparing adopters and non-adopters. PSM is a statistical technique that adjusts for confounding variables across a sample population, enabling more accurate estimation of treatment effects. As outlined by Caliendo and Kopeinig (2008), the implementation of PSM involves several key steps: first, estimating propensity scores using a binary model; second, selecting an appropriate matching algorithm; third, verifying the common support condition; and fourth, assessing the quality of the matching between the treatment and control groups. The following are the steps involved in PSM:\n\nStep 1: Model Specification\n\nThe logistic model was chosen for this study due to the robustness of its parameter estimations, which stems from the assumption that the error term in the equation follows a logistic distribution (Baker and Melino, 2000; Ravallion, 2007). Therefore, the Logit model was used to estimate the probability of smallholder farmers’ adoption of CSAPs allotted to socio-economic, agro-ecological and institutional characteristics. Therein, a dependent variable considered a value of 1 for CSAPs adoption and 0 for non-CSAPs adopters.\n\nIn line with Pindyck and Rubinfeld (1981), the cumulative logistic probability function is specified as follows;\n\nExpressing the logistic model in terms of odds and log-odds aids in interpreting the coefficients (Gujarati, 1995). The odds ratio quantifies the relative probability of an individual participating (Pi) versus not participating (1-Pi). The probability of non-participation can be calculated as:\n\nAlternatively,\n\nTaking the natural logarithms of equation (3.5) will give the logit model as indicated below.\n\nIf consider a disturbance term, μi, the logit model becomes\n\nSo, the binary logit will become:\n\nWhere pp is CSAPs adoption, f(X) is the dependent variable project participation and X is a vector of observable covariates of the households. The dependent variable will take a value of 1 for CSAPs adoption and 0 for non-adopters.\n\nIn addition to the estimated coefficients, the marginal effects of the change in the explanatory variables on the probability of CSAPs adoption are also estimated. The interpretation of these marginal values will be dependent on the unit of the measurement for explanatory variables.\n\nWhen an explanatory variable is binary, the marginal effects provide a reasonable estimate of the change in the likelihood of the outcome variable (Y = 1) evaluated at representative values of the regressors, such as their means.\n\nStep 2: Identifying the Common Support Region and Conducting Balancing Tests\n\nThe region where the propensity score distributions of the treatment and comparison groups overlap is known as the area of common support. This needs to be identified. However, if there is a systematic difference in the observed characteristics between the dropped non-adopters of CSAPs and the retained non-adopters, sampling bias may still occur. These differences should be closely monitored to aid in the interpretation of the treatment effect. Furthermore, balancing tests can be conducted to check if the mean of the covariates (X) and the average propensity score are equal within each quantile of the propensity score distribution.\n\nFor PSM to be effective, the treatment and comparison groups must be well-balanced based on their observed covariates (X), as similar propensity scores are derived from similar observed characteristics. Achieving balance necessitates that the covariate distributions of the treated and untreated units are indistinguishable. Formally, this requires verifying that the conditional distributions P(X|T=1) and P(X|T=0) are equivalent. Here’s a version with reduced similarity:\n\nStep 3: Matching adopters to non-adopters\n\nSelecting an available data matching algorithm is the third stage. Selecting control subjects who are matched to treated subjects based on context factors that the investigator feels should be tracked is a standard process known as matching. A different one might use comparable criteria. according to propensity score, divide adopters against non-adopters. Kernel-based matching (KBM), radius matching (RM), and closest neighbour matching (NN) are the most often used matching algorithms.\n\nStep 4: Matching quality\n\nMatching quality tests could be conducted in the fourth step. Whether or whether the matching method can balance the distribution of different variables is determined by checking for matching, irrespective of quality. If there are discrepancies, it could be a sign of insufficient matching, and corrective action is advised (Caliendo & Kopeinig, 2008). The next action is to determine if the treatment caused a difference in the impact indicators.\n\nThe difference between the mean outcome of matched adopters and nonadopters with common support conditional at the propensity score provides the average treatment effect at the treated (ATT).\n\nStep 5: Sensitivity analysis\n\nLastly, to verify the strength of the conditional independence assumption, a sensitivity analysis will be performed. Sensitivity analysis will also be used to examine whether the influence of an unmeasured variable on the decision-making process is significant enough to compromise the matching strategy (Ali & Abdulai, 2010). The sensitivity analysis (r-bounds test) will be performed using the Rosenbaum bound sensitivity test.\n\nThe study was conducted by the researcher and two supervisors, adhering to principles of integrity, objectivity, openness, respect for research participants, respect for intellectual property, confidentiality, informed consent, fidelity, and honesty. The researcher and supervisors take full responsibility for their actions and publications, ensuring that all agreements are intended to be upheld. The study was approved by the University of Zambia Directorate of Research and Graduate Studies (NASREC) on March 18, 2024, and is registered under NASREC IRB No. 00005465 (IORG No. 0005376). The principal researcher provided a written consent form for research participants to participate in the household survey, conforming to the research ethics guidelines of the University of Zambia and Haramaya University.\n\n\n3. Results and discussion\n\nCharacteristics of the participant smallholder farmers\n\nThe household survey consisted of 194 randomly selected smallholder farmers from the research area. These farmers were interviewed about their crop production and the application of various Climate-Smart Agriculture (CSA) practices. The study presents the findings of the household survey, beginning with the demographic characteristics of the participants (Table 1), followed by sections on crop production and productivity, adoption of CSA practices, constraints on the adoption of CSA practices, effects of CSA practices on crop productivity, and factors affecting crop productivity. A total of 339 field plots of various crops were surveyed from the 194 farmer participants. Table 2 provides detailed demographic and socio-economic data on the respondents. The mean age was 46 years (standard deviation: 14.59), and the majority of households (62.18%) were male-headed, with 69.43% of respondents being married. The mean years of formal education were 5.49 (standard deviation: 3.5), and the mean years of farming experience were 26.22 (standard deviation: 15.55). Respondents had lived in the area for an average of 30.92 years (standard deviation: 18.68). The average family size was 5.42 (standard deviation: 2.14). The average total annual income was K5,472.68 (USD 331.68, at an exchange rate of K16.5 per USD), with a standard deviation of 7,626.52. Additionally, 57.51% of respondents reported participating in off-farm activities. Regarding agricultural practices, 78.76% used improved seed varieties, and the average farm size was 3.396 hectares (standard deviation: 3.363). All land was under customary tenure (100%), with the mean cultivated land being 1.83 hectares (standard deviation: 1.45). On average, smallholder farmers grew two different crops, with a standard deviation of 0.930.\n\nCrops grown by smallholder farmers\n\nRegarding the crops that the farmers grew, the study discovered that the most common crop was maize, which was recorded in 194 crop plots. Groundnuts were reported in 99 plots, sunflower in 69 plots, and soy beans in 16 plots. (Table 2). It was said that the other crops—cowpea, sweet potatoes, millet, cotton, and bambara nuts—were produced in small plots.\n\nClimate-smart agriculture practices adopted by smallholder farmers\n\nThe study’s findings shed light on the adoption of various conservation agriculture techniques across the surveyed field plots. Among these practices, pot-holing (basin) emerged as the most widely implemented method, with 61 plots (17.99%) employing this technique. Closely following was multi-cropping, which was practiced on 50 plots, accounting for 14.75% of the total. Minimum tillage, a soil conservation approach, was utilized on 34 plots, representing 10.03% of the survey sample. The ripping technique, which involves creating furrows in the soil, was observed on 32 plots (9.44%). Furthermore, 18 plots (5.31%) incorporated crop rotation as a means of maintaining soil fertility and controlling pests and diseases. The application of manure, a natural fertilizer, was recorded on 11 plots (3.24%), while alley cropping, a system that combines crops with trees or shrubs, was adopted on 9 plots (2.65%) (Table 3). It is noteworthy that the remaining conservation agriculture techniques were tested on fewer than 10 plots each, indicating their relatively limited implementation within the surveyed area.\n\nNumber of climate smart agriculture practices adopted by smallholder farmers\n\nThe study’s findings, as presented in Table 4, shed light on the extent of conservation agriculture (CSA) practice adoption among the surveyed plots. Notably, a substantial number of plots, 167 (49.26%), did not incorporate any CSA techniques whatsoever. This highlights a significant gap in the implementation of sustainable agricultural practices within the surveyed area. On the other hand, a considerable portion of the plots, 123 (36.28%), had adopted at least one CSA practice, indicating a positive step towards embracing more environmentally friendly farming methods. Additionally, 4 plots (12.68%) had implemented two different CSA practices simultaneously, demonstrating a more comprehensive approach to sustainable agriculture. Interestingly, the data revealed that a smaller number of plots had adopted multiple CSA techniques concurrently. Specifically, four plots had incorporated three distinct CSA practices, while one plot had implemented an impressive four different CSA practices. Furthermore, another plot stood out by adopting a remarkable five separate CSA techniques. Despite these instances of multiple CSA practice adoption, the overall findings suggest that the majority of farmers within the surveyed area were either not implementing any CSA techniques or had adopted only a single practice. This observation underscores the potential for further education and awareness-raising efforts to encourage the widespread adoption of multiple sustainable agricultural practices, ultimately contributing to improved soil health, crop productivity, and environmental conservation.\n\nQuantities harvested for various crops (kg)\n\nThe survey data presented in Tables 5, 6 offers valuable insights into the crop cultivation patterns and yield outcomes among the surveyed farming community. Notably, the crops that emerged as the most prevalent choices among farmers were soybeans, maize (corn), groundnuts, and sunflowers. Across all crop types, the average harvest weight recorded was 1223.51 kg, accompanied by a substantial standard deviation of 1442.82. This variation in yields highlights the diverse factors that can influence agricultural productivity, including soil conditions, farming practices, environmental variables, and access to resources. When examining the individual crop yields, maize stood out as a prominent crop, with an impressive average harvest weight of 1766.57 kg. However, the high standard deviation of 1594.23 suggests significant variations in maize yields among farmers, potentially attributable to differences in cultivation techniques, seed quality, or localized environmental conditions. Groundnuts, a staple crop in the region, exhibited an average harvest weight of 511.08 kg, with a standard deviation of 605.07. This relatively lower yield, coupled with the substantial variation, may indicate challenges faced by farmers in optimizing groundnut production, such as pest or disease pressures, or limitations in access to appropriate inputs and knowledge. Sunflowers, a valuable oilseed crop, yielded an average harvest weight of 609.67 kg, with a standard deviation of 513.02. While the average yield appears moderate, the substantial variation observed could be attributed to factors like soil fertility, water availability, or sunflower variety selection. Notably, soybeans emerged as a crop with significant yield potential, boasting an average harvest weight of 1007.5 kg. However, the remarkably high standard deviation of 1835.615 points to substantial disparities in soybean yields among individual farmers. This variability may stem from differences in cultivation practices, access to quality seeds, or the adoption of specific agricultural techniques tailored for soybean production. These findings not only underscore the crop preferences of the surveyed farmers but also highlight the need for targeted interventions and support measures to address the observed yield variations. By identifying and addressing the underlying factors contributing to these disparities, efforts can be made to enhance agricultural productivity, promote sustainable farming practices, and ultimately improve the livelihoods of smallholder farmers in the region.\n\nProductivity of various crops (Yield (kg) per hectare)\n\nThe study’s findings shed light on the crop productivity levels observed among the surveyed farming communities. Considering the overall yield across all crop types, the average yield per hectare stood at an impressive 1316.60 kg, although the substantial standard deviation of 1214.13 suggests significant variations in individual yields (Table 7). Focusing specifically on maize, a crucial staple crop, the mean yield per hectare was calculated to be 1682.52 kg. However, the high standard deviation of 1325.87 indicates substantial disparities in maize yields among farmers, potentially influenced by factors such as soil fertility, farming practices, and environmental conditions. Groundnuts, another important crop in the region, exhibited an average yield of 822.90 kg per hectare, accompanied by a standard deviation of 547.88. This variation in yields could be attributed to challenges faced by farmers in optimizing groundnut production, including pest or disease pressures, access to quality inputs, or knowledge gaps. Sunflower cultivation yielded an average of 962.79 kg per hectare, with a relatively lower standard deviation of 437.38, suggesting more consistent yields among farmers. This could be a result of better-adapted cultivation practices or more uniform environmental conditions suitable for sunflower growth. Soybeans, a valuable crop with growing demand, recorded an average yield of 808.40 kg per hectare. The standard deviation of 426.74 indicates moderate variations in soybean yields, which could be influenced by factors such as seed quality, planting techniques, or soil management practices. These findings not only provide insights into the productivity levels of various crops but also highlight the need for targeted interventions and support measures to address the observed yield variations. By identifying and addressing the underlying factors contributing to these disparities, efforts can be made to enhance agricultural productivity, promote sustainable farming practices, and ultimately improve the livelihoods of smallholder farmers in the region.\n\nImpact of climate-smart practices on crop productivity among smallholder farmers\n\nThe study examined the impact of Climate-Smart Agriculture (CSA) techniques on the crop yields of smallholder farmers. It was found that farmers who adopted CSA practices experienced a 20.20% higher crop yield compared to those who did not adopt these practices (Table 8). The difference was statistically significant, with a p-value of 0.027 (p < 0.05). These results suggest that the adoption of CSA practices leads to increased crop yields.\n\n*** <1%,\n\n** <5% and\n\n* <10%; Author’s calculation using Stata 15MP.\n\nImpact of climate-smart practices on maize productivity among smallholder farmers\n\nThe study utilized propensity score matching analysis to specifically assess the impact of CSA on maize productivity (Table 9). The findings indicated that CSA adoption led to a 21.50% increase in maize yield compared to non-adoption. This significant increase in maize yield, with a p-value of 0.035 (p < 0.05), demonstrates the positive effect of CSA practices on maize productivity.\n\n*** <1%,\n\n** <5% and\n\n* <10%; Authors’calculation using Stata 15MP.\n\nFactors affecting smallholder farmers’ adoption of climate-smart agricultural\n\nThe study employed logistic regression analysis to examine the factors influencing the adoption of Climate-Smart Agricultural (CSA) practices among farmers. The findings revealed that age played a pivotal role, with older farmers being more inclined to embrace sustainable agricultural methods. Specifically, the results indicated a statistically significant positive relationship between age and the adoption of CSA practices, with a p-value of 0.0000 (p < 0.001). Farmers within the age groups of 40-55 years and above 55 years were found to have a higher rate of adopting CSA practices in the study area. Interestingly, the research uncovered an inverse correlation between prior farming experience and the willingness to implement climate-smart farming techniques. Contrary to expectations, farmers with more years of experience in the agricultural sector were less likely to adopt CSA practices, a finding that was statistically significant at a p-value of 0.0000 (p < 0.001). Income level was also identified as a significant factor, with a positive relationship between higher income and the adoption of CSA practices. This relationship was statistically significant at a p-value of 0.0640 (p < 0.1) (Table 10). This finding aligns with Zakaria et al. (2020), who demonstrated that factors such as experience in rice cultivation, access to media and training, and perceived decrease in rainfall quantity positively influenced the adoption of climate-smart agricultural technologies. Conversely, larger farm sizes, greater distances between farmers’ homes and farm sites, location, and reported temperature rises were found to hinder the adoption of these technologies. While the present study highlighted age and income as facilitators of CSA adoption, it contrasted with previous research by Saha et al. (2019), which identified factors like education, occupation, family size, farm size, climate change adaptation techniques, cattle ownership, market accessibility, information access, training, organizational affiliations, and climate change perceptions as influential determinants. This suggests that while higher income levels facilitate the adoption of CSA practices, other factors such as farm size, accessibility, and perceived climatic changes can pose challenges to the adoption of these technologies.\n\n*** <1%,\n\n** <5% and\n\n* <10%; Author’s calculation using Stata 15MP.\n\nThis study revealed several intriguing findings regarding the factors influencing the adoption of climate-smart agricultural practices among farmers. Gender played a significant role, with a p-value of 0.0660 (p < 0.1), indicating that the gender of the farmer had a notable impact on the likelihood of embracing sustainable farming methods.\n\nInterestingly, farm size exhibited an inverse relationship with the adoption of climate-smart practices, as evidenced by the negative significant effect observed at a p-value of 0.0050 (p < 0.01). This suggests that farmers with larger landholdings were less inclined to implement these environmentally-friendly agricultural techniques.\n\nOn the other hand, livestock quantity emerged as a positive driving force, exerting a significant influence on the adoption of climate-smart agriculture with a p-value of 0.0180 (p < 0.1). Farmers with more substantial livestock holdings were more likely to adopt these sustainable practices, potentially due to the perceived benefits or increased resources associated with livestock ownership.\n\nNotably, access to climate information had an unexpected negative impact on the adoption of climate-smart agriculture, with a p-value of 0.0060 (p < 0.01). This counterintuitive finding raises questions about the effectiveness of climate information dissemination and the potential barriers that may hinder its translation into practical implementation. These findings align with the research conducted by Kurgat et al. (2020), which highlighted female ownership of farm assets, farm location, and household resources as critical determinants of climate-smart agricultural adoption in Tanzania. Similarly, Aryal et al. (2018) concluded that various factors, including household characteristics, market access, and primary climate hazards, influenced the probability and level of implementing different climate-smart practices among smallholder farmers. However, in contrast, a study by Abegunde et al. (2019) found that marital status, education level, fertilizer use, credit access, and access to extension services did not significantly impact the adoption of climate-smart agricultural practices. This divergence in findings underscores the complex interplay of factors influencing the embracement of sustainable agricultural methods and the potential variations across different contexts and regions.\n\nFactors affecting smallholder farmers’ crop productivity\n\nTo identify the variables influencing agricultural yield, the study conducted a Cobb-Douglas production analysis (Table 11). The findings demonstrated that income has a positive and significant effect on agricultural productivity; specifically, productivity increases by 0.002% as farmers’ income levels rise. This relationship is statistically significant, with a p-value of 0.0040 (p < 0.01). According to a study by Urgessa (2015), the land-labor ratio, the use of pesticides and fertilizers, the amount of manure used, and household size are the main factors affecting agricultural labour and crop productivity. WenJing et al. (2021) examined income disparities across household quartiles and found that while middle-class and upper-middle-class households may benefit more from renting out their farmland, households with high on-farm incomes are less likely to expand their farm size through farmland rental. Fertilizer use significantly improved crop productivity, with crop yield increasing by 0.12% for every unit increase in fertilizer use. This relationship was statistically significant, with a p-value of 0.0000 (p < 0.001). Additionally, Du et al. (2020) demonstrated that long-term applications of synthetic fertilizers and manure enhance soil productivity and crop yields.\n\n*** <1%,\n\n** <5% and\n\n* <10%; Author’s calculation using Stata 15MP.\n\nThe study unveiled a complex interplay of factors influencing crop productivity among smallholder farmers. Notably, farm size exhibited an inverse relationship, with larger landholdings leading to a 6.52% decrease in crop yields. This counterintuitive finding may be attributed to factors such as resource constraints, management challenges, or diminishing returns associated with larger land areas. In contrast, livestock quantity emerged as a significant driver of crop productivity, with each additional unit of livestock owned contributing to an 0.86% increase in crop yields. This statistically significant effect, with a p-value of 0.0001 (p<0.001), highlights the synergistic relationship between livestock and crop cultivation. Livestock not only provide valuable manure and animal draught power but also serve as a source of income that can be reinvested in technologies that enhance crop production capabilities (Anderson, 1989; Beedy et al., 2010). Remarkably, the adoption of climate-smart agricultural (CSA) practices was found to have a profoundly favorable impact on crop productivity. When an additional farmer implemented these sustainable farming methods, the average yield among farmers improved by a staggering 13.49%, a statistically significant effect with a p-value of 0.0720 (p < 0.1). This finding underscores the potential of CSA practices to boost crop yields and contribute to overall agricultural productivity while promoting environmental sustainability. Corroborating these results, the study by Mujeyi et al. (2021) also demonstrated that the adoption of climate-smart agriculture significantly contributed to increased crop yields among smallholder farmers operating within an integrated crop-livestock system. This alignment across different research contexts reinforces the potential benefits of embracing sustainable agricultural practices and highlights the importance of an integrated approach. Furthermore, the study explored the impact of demographic characteristics on crop productivity. While marital status and the education level of the household head exhibited modest contributions of 0.07% and 0.098%, respectively, household size played a more significant role, contributing 0.2% to smallholder farmers’ crop productivity. These findings resonate with the research conducted by Serote et al. (2021), which highlighted the influence of smallholder farmers’ household demographics and institutional characteristics on the adoption of climate-smart agriculture and, consequently, crop productivity. This convergence of results across multiple studies underscores the complex interplay of factors that shape agricultural outcomes and the potential for targeted interventions to enhance productivity and sustainability. By addressing key drivers such as farm size, livestock integration, adoption of climate-smart practices, and demographic considerations, policymakers and development organizations can develop tailored strategies to support smallholder farmers in achieving improved crop yields while promoting environmental resilience.\n\n3.2.1 Climate-smart practices impact on crop productivity\n\nThe study aimed to assess the impact of implementing Climate-Smart Agricultural (CSA) practices on crop productivity among smallholder farmers in the Nyimba district of Zambia. Additionally, it sought to identify the factors influencing the adoption of CSA practices and crop production among smallholder farmers in the region. The data analysis revealed that the crop yields of smallholder farmers who adopted CSA practices were 20.20% higher than those of non-adopters. Furthermore, the study found that smallholder farmers who adopted CSA practices experienced a 21.50% increase in maize yield compared to those who did not adopt these practices. These findings clearly demonstrate that the implementation of climate-smart farming methods can significantly boost crop productivity for smallholder farmers. By adopting CSA practices, smallholder farmers have the potential to substantially increase their crop yields, thereby enhancing their agricultural productivity and food security.\n\nSeveral studies have investigated the impact of Climate-Smart Agricultural (CSA) practices on crop productivity, food security, and soil quality. Abegunde et al. (2022) conducted a study on the effect of CSA on household food security among 327 smallholder farmers in Nigeria, using binary and multinomial logistic regression models. Their findings revealed that the adoption of CSA practices significantly and favorably affected household food security. Additionally, agricultural revenue and income from non-farm sources positively influenced household food security. In a similar vein, Mossie (2022) assessed the impact of CSA technology, specifically wheat row planting, on productivity in Southern Ethiopia using propensity score matching. The study found that row planting had a favorable and significant effect on productivity, with adopters producing 1368 kg of wheat per hectare more than non-adopters, highlighting the positive impact of this CSA practice on yield. Tadesse et al. (2021) examined the impact of CSA practices in Ethiopia on soil carbon, crop productivity, and fertility. Their results demonstrated a 30–45% higher yield under CSA practices compared to the control (p < 0.05). Furthermore, CSA interventions slightly increased soil pH and significantly increased plant-available total nitrogen and phosphorus by 2.2–2.6 and 1.7–2.7 times, respectively, compared to the control. This study highlights the potential of CSA practices to enhance crop yield and nutrient availability, contributing to the resilience of resource-poor farmers in the face of climate change. Kichamu-Wachira et al. (2021) also reported similar findings on the positive effects of CSA practices on crop yields, soil carbon, and nitrogen pools in Africa. Their study concluded that CSA practices represent an advanced agricultural technology compared to conventional farming, enhancing food production while promoting climate mitigation and soil quality. Moreover, Amadu et al. (2020) found that 53% of CSA adopters among 808 smallholder farmers’ households in southern Malawi experienced increased maize yields during the drought year of 2016. Similarly, Fentie and Beyene (2019) revealed a significant positive impact of CSA adoption on crop yield per hectare using a propensity score matching model. These studies collectively highlight the potential of CSA practices to enhance crop productivity, food security, and soil quality, contributing to the resilience of smallholder farmers in the face of climate change and variability.\n\n\nConclusion\n\nThe study shows that a number of factors, including the amount of education held by farmers, the size of their households, the use of fertiliser, the age and gender of the household head, their farming experience, whether or not they own livestock, their annual household income, the size of their farmland, their access to climate-related information, and their level of farming experience, all have a significant impact on the adoption of climate-smart agriculture practices and crop productivity among smallholder farmers in Zambia’s Nyimba district. These elements work together to influence the decision-making procedures, methods for allocating resources, and ability of smallholder farmers to apply sustainable farming practices. It is advised to improve educational and training programs geared towards smallholder farmers, emphasising climate-smart techniques, sustainable land management practices, and efficient resource utilisation, to address the obstacles and promote adopting climate-smart agriculture practices. Furthermore, farmers will be able to make educated decisions and modify their agricultural methods if information relating to climate change is made timely and accessible through improved channels of distribution. Improving smallholder farmers’ access to vital resources is critical to promoting the adoption of climate-smart practices and raising crop yield. These resources include enhanced seed varieties, financial facilities, and agricultural inputs. Encouraging diversification techniques, like combining crop farming with animal raising, can boost household income and resilience.\n\nIn addition, it is critical to improve agricultural extension services by offering smallholder farmers information, guidance, and technical assistance, especially concerning climate-smart agricultural methods and sustainable land management. Achieving successful adoption also requires addressing gender gaps by empowering women farmers through decision-making processes, education, and resource availability. Farmer organisations and cooperatives can be formed to improve access to resources and markets, information exchange, and group action. To sum up, further support for sustainable agricultural development can be provided by creating and enacting laws and policies that promote the use of climate-smart farming methods. Examples of these include tax breaks, subsidies, and payments for ecosystem services.\n\n\nEthics and consent\n\nThe study was approved by the University of Zambia Directorate of Research and Graduate Studies (NASREC) on March 18, 2024, and is registered under NASREC IRB No. 00005465 (IORG No. 0005376). The principal researcher provided a written consent form for research participants to participate in the household survey, conforming to the research ethics guidelines of the University of Zambia and Haramaya University.\n\n\nAuthor contributions\n\nAuthors contributed in the following ways: “Conceptualization, C.P. and F.S.; methodology, C.P.; software, C.P.; validation, S.C., F.S.; formal analysis, C.P.; investigation, C.P.; resources, S.M.; data curation, C.P.; writing—original draft preparation, C.P.; writing—review and editing, S.M.; supervision, F.S. and S.C. All authors have read and agreed to the published version of the manuscript.” Authorship must be limited to those who have contributed substantially to the work reported.",
"appendix": "Data availabity statement\n\nZenodo: Adoption of Climate-Smart Agricultural Practices and Its Impact on Crop Productivity: A Case Study of Smallholder Farmers in Nyimba District, Zambia [Data set]. Zenodo. https://doi.org/10.5281/zenodo.11258819 (Chavula, P., et al., 2024)\n\nThis project contains the following underlying data:\n\n• Edited_Survey data 28.03.2022.dta\n\nData are available under the terms of the Creative Commons Attribution 4.0 International\n\n\nAcknowledgments\n\nThe authors express their sincere gratitude for the invaluable funding support provided by the World Bank through the African Centre of Excellence for Climate Smart Agriculture and Biodiversity Conservation Management. 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Sci. 2022; 3: 20.\n\nTadesse M, Simane B, Abera W, et al.: The effect of climate-smart agriculture on soil fertility, crop yield, and soil carbon in southern ethiopia. Sustainability. 2021; 13(8): 4515. Publisher Full Text\n\nTimberlake J, Chidumayo E, Sawadogo L: Distribution and characteristics of African dry forests and woodlands.The dry forests and woodlands of Africa.Routledge; 2010; pp. 11–41.\n\nUrgessa T: The Determinants of Agricultural Productivity and Rural Household Income in Ethiopia. Ethiop. J. Econ. 2015; 24(2): 63–91.\n\nWenJing H, ZhengFeng Z, XiaoLing Z, et al.: Farmland Rental Participation, Agricultural Productivity, and Household Income: Evidence From Rural China. Land. 2021; 10(9): 1–22.\n\nZakaria A, Alhassan SI, Kuwornu JKM, et al.: Factors Influencing the Adoption of Climate-Smart Agricultural Technologies Among Rice Farmers in Northern Ghana. Earth Syst. Environ. 2020; 4(1): 257–271. Publisher Full Text"
}
|
[
{
"id": "305606",
"date": "10 Aug 2024",
"name": "Ibsa Dawid",
"expertise": [
"Reviewer Expertise Climate-Smart Agriculture and Agricultural Economics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. Is the work clearly and accurately presented and does it cite the current literature? The work is not clearly accurate, not briefly presented and it’s bulky, not hit the target. Partly……, why because now we are in 2024, but the authors cited even ten years back reference, the climate change is the current issue so it’s appropriate if the author use the recent literatures not more than the last five years.\n2. Is the study design appropriate and is the work technically sound? Partly, some steps are there but they are not fully designed appropriately.\n3. Are sufficient details of methods and analysis provided to allow replication by others? No, the methods and analysis provided are not sufficient.\n4. ….is the statistical analysis and its interpretation appropriate? Not applicable. The statistical analysis is not applicable, for example a Cobb-Douglas production analysis……for what purpose the author used this analysis in the document? I did not seen it. The propensity sore matching is not well interpreted by with the steps. The formula for all the existing steps should be discussed.\n5. Are all the source data underlying the results available to ensure full reproducibility? No, the results presented do not seem to be fully consistent with the study's objectives, and they are not described in sufficient detail. The outcomes from Tables 10 and 11 are not clearly articulated, and there appear to be some inaccuracies in the model's results. It seems that the author may lack sufficient statistical experience, as there is difficulty in distinguishing which values are significant and which are not. The values in the tables are listed as they appear in the model, but it would be more effective if the results were first described, then compared with previous findings. Regarding Tables 10 and 11, while they seem to address the study's objectives, the results are not adequately explained. For instance, the values indicated in the tables may not align with established scientific standards. For example, in Table 11, the variable \"household size\" shows a t-value of 1.2800 and a p-value of 0.0012. It's unclear how these calculations were performed, as the conclusion drawn—that the variable significantly influenced farmers' crop productivity—does not seem accurate. Additionally, the interpretation of other variables may also require reconsideration. As a note, a variable is generally considered to have a significant influence if its t-value or z-value is greater than 1.65 at a 10% significance level. 6. Are the conclusions drawn adequately supported by the results? No, the conclusions drawn do not seem to be fully supported by the study's results. For example, the authors conclude that all variables significantly influenced CSA practices and crop production. However, this does not align with the results presented in Table 10, where gender, farm size, livestock, and access to climate information did not significantly influence the adoption of CSA. Despite this, the authors concluded that these variables were significant and influenced adoption decisions. Similarly, in Table 10, the farm size shows a z-value of -0.4500 and a p-value of 0.0050, which raises questions about the conclusions drawn. A more robust justification would be helpful here. The same concern applies to the results in Table 11, where variables such as marital status, education, and household size were not shown to significantly influence crop productivity based on the results, which contradicts the conclusions made by the authors.\n\nNot Approved: “I have read this submission. I believe I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.”\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "323712",
"date": "10 Oct 2024",
"name": "Rao Sabir Sattar",
"expertise": [
"Reviewer Expertise livelihood vulnerability",
"climate change adaptation",
"extension methods"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article titled \"Factors Influencing Climate-Smart Agriculture Practices Adoption and Crop Productivity among Smallholder Farmers in Nyimba District, Zambia\" offers an insightful analysis into the drivers behind the adoption of climate-smart agricultural (CSA) practices and their effect on crop productivity. While the study is well-structured and addresses critical concerns of smallholder farmers in the context of climate change, there are, in my opinion, several areas of strength and opportunities for improvement.\nStrengths: The study's focus on climate-smart agriculture (CSA) adoption is highly pertinent, particularly given the increasing threats of climate change on smallholder farmers, whose livelihoods depend heavily on climate-sensitive agricultural activities. It fills a critical research gap by examining both the factors driving CSA adoption and the tangible benefits of CSA in terms of crop productivity. The use of logistic regression and propensity score matching is appropriate and well-explained. These methods provide robust insights into the causal relationship between CSA adoption and increased crop productivity, allowing the study to demonstrate clear statistical correlations between the independent and dependent variables. The study examines a wide array of factors influencing CSA adoption, such as education, household size, farming experience, and access to climate-related information. This thoroughness highlights the complexity of decision-making processes among smallholder farmers and presents a holistic view of the influencing factors. The study’s findings provide actionable insights for policymakers and stakeholders. The clear demonstration of the positive impact of CSA practices on crop productivity, especially maize yields, can inform policy interventions aimed at promoting CSA in regions similar to Nyimba District. Additionally, the focus on educational level and access to information emphasizes the need for targeted extension services.\nAreas for Improvement: While the article presents a detailed account of the findings, the discussion could benefit from deeper engagement with the implications of the results. For instance, how do the identified factors interact with one another, and are there synergies or trade-offs in adopting CSA practices? Further, it would be helpful to discuss the potential barriers that may prevent broader adoption of CSA practices, beyond those identified by the logistic regression model. The paper could strengthen its impact by better contextualizing the results within the broader literature on CSA adoption in Africa and other developing regions. A comparative analysis with other regions facing similar climate challenges would offer a more nuanced understanding of how the findings fit into the global or regional discourse on CSA. While the study hints at policy implications, the recommendations could be made more explicit. For example, based on the factors influencing CSA adoption, what specific interventions could policymakers implement to enhance adoption rates? The paper should elaborate on the role of agricultural extension services, access to credit, or other mechanisms that can facilitate the uptake of CSA practices. Although the study is methodologically sound, a clearer discussion of its limitations would enhance transparency. For example, were there any challenges in the data collection process, or potential biases in the selection of farmers? Additionally, suggesting avenues for future research, such as longitudinal studies on the long-term impacts of CSA adoption, would strengthen the study's contribution to the field.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12716",
"date": "03 Dec 2024",
"name": "chavula petros",
"role": "Author Response",
"response": "Dear Reviewers, I have thoroughly reviewed your previous comments and have addressed each one accordingly. I look forward to receiving any further feedback at your earliest convenience. Best regards,"
}
]
}
] | 1
|
https://f1000research.com/articles/13-815
|
https://f1000research.com/articles/13-1475/v1
|
03 Dec 24
|
{
"type": "Research Article",
"title": "Association of Triglyceride glucose index with the outcomes of Ischemic stroke.",
"authors": [
"Chaand Bibi",
"Ahmad Hassan Khan",
"Muhammad Kashif",
"Maaz Khan",
"Syed Muhammad Shoaib Iftikhar",
"Chaand Bibi",
"Ahmad Hassan Khan",
"Maaz Khan",
"Syed Muhammad Shoaib Iftikhar"
],
"abstract": "Background Ischemic stroke is a primary contributor to both mortality and disability on a global scale. The triglyceride-glucose index (TyG index), which measures insulin resistance, has been found as a possible predictor of outcomes of cerebrovascular events.\n\nObjective To examine the correlation between TyG index and outcomes in patients diagnosed with ischemic stroke.\n\nMethods This retrospective analysis of 200 patients diagnosed with ischemic stroke was carried out at the department of medicine, Khyber Teaching Hospital, Peshawar between 1st August 2022 and 31st December 2023. Triglyceride/glucose ratio was determined using the formula TyG = ln [Fasting triglycerides (mg/dl)/Fasting glucose (mg/dl)]/2. Patients were categorized into two Group A (TyG index < 8.8) and Group B (TyG index > 8.8). Demographic data, clinical features, and stroke outcomes, such as death and functional status (assessed by the modified Rankin Scale [mRS]), were compared between the two groups.\n\nResults Group A contained (112) patients and Group B (88). Both Group A and Group B had 51.8% (n=58) and 51.1% (n=45) male patients respectively. The mean age of patients in Group A was 65.4 ± 10.2 years and 67.1 ± 11.5 years in group B. 30-day mortality in group A was 8.0% (n=9) and 18.2% (n=16) in group B (p value 0.03). The median mRS score at 3 months in group A was 2.5 versus 3.5 in group B (p value = 0.02). Patients in Group B had longer hospital stay (10.5 ± 3.1days vs. 8.2 ± 2.4days, p = 0.01) and higher frequency of major adverse cardiovascular events (MACE) (15% vs. 7%, p = 0.05).\n\nConclusion In ischemic stroke patients, 30-day mortality was more common with TyG index >8.8 and the modified Rankin Scale (mRS) functional status at 3 months was better in TyG index <8.8.",
"keywords": [
"Ischemic stroke",
"Outcomes Assessment",
"Triglyceride-Glucose Index (TyGI)",
"Insulin Resistance"
],
"content": "Introduction\n\nIschaemic stroke is one of the leading cause of mortality and morbidity across the globe, resulting from occlusion to blood supply to the brain leading to profound neurological deficits.1 Although there have been advances in the initial management and rehabilitation of stroke patients, outcomes still vary. This underlies the importance of having reliable markers for anticipating prognosis that may enable the choice of appropriate therapy and an improvement in patient care.2 The triglyceride-glucose (TyG) index was developed a new indicator which is calculated from fasting triglyceride and glucose levels; it could serve as a surrogate measure for insulin resistance in cardiovascular diseases.3,4\n\nInsulin resistance is an essential determinant of atherosclerosis development and cardiovascular events both of which are major risk factors for ischemic stroke.5 For its simplicity, relative inexpensive and its strong association with insulin resistance, TyG index has generated considerable interest making it practical tool in clinical settings.6 Numerous studies have shown that TyG index has excellent predictive performance for cardiovascular diseases such as coronary artery disease and hypertension. However, the extent to which it is linked to the outcomes of ischemic stroke has not been well investigated.7,8\n\nExamining the correlation among the TyG index and ischemic stroke outcomes might provide significant knowledge about the processes that determine stroke prognosis and help identify people at a high risk.9 This study examined the TyG index and clinical outcomes in ischemic stroke patients, including death and functional status, in a tertiary care hospital with resource limited settings. Results of the study might have important consequences for clinical practice, potentially resulting in the integration of the TyG index into standard evaluation methods for patients with ischemic stroke. This would facilitate the implementation of more precise treatment measures, thereby enhancing patient outcomes. Moreover, this study has the potential to add to the increasing amount of information that supports the significance of insulin resistance in the development of stroke. This, in turn, might lead to more research being conducted on specific therapies for those at high risk of stroke.\n\n\nMethods\n\nThis descriptive retrospective study was carried out at the department of Medicine, Khyber Teaching Hospital, Peshawar, Pakistan.\n\nThe study was carried out during the period 1st August 2022 and 31st December 2023.\n\nInclusion criteria\n\nA total of 200 male and female patients aging 50 years or above diagnosed with ischemic stroke were enrolled. Confirmation of ischemic stroke was carried out clinically and ruling out hemorrhage through CT brain.\n\nExclusion criteria\n\nPatients with hemorrhagic stroke, transient ischemic attack (TIA), severe cardiopulmonary compromised patients, inadequate clinical data and those who were lost to follow-up were excluded.\n\nThe TyG index was calculated using the formula:\n\nBased on the TyG index values, patients were divided into two groups:\n\nGroup A: TyG index less than 8.8\n\nGroup B consists of patients with a TyG index greater than or equal to 8.8.\n\nPrimary outcomes: Primary outcomes were 30-day post-stroke mortality and functional status at 3 months. Death of the patient within 30 days after stroke with stroke as cause of death was called 30-day post-stroke mortality. Functional status was assessed using modified Rankin Scale (mRS) at 3 months after stroke.\n\nSecondary outcome: Secondary outcomes were hospital stay and Major adverse cardiovascular events. Hospital stay was defined as the number of days spent in the hospital from admission till discharge. Frequency of major adverse cardiovascular events (MACE) including composite of myocardial infarction, another episode of stroke and all-cause mortality occurring during the three months observation period.\n\nInformation was gathered from computerized medical records. The gathered data included demographic data such as age and gender, clinical factors including a history of diabetes, hypertension, dyslipidemia, smoking status, BMI, education, socioeconomic status and employment status, fasting lipid profile including fasting triglyceride level and fasting blood glucose level. TyG index was calculated using the equation TyG index = ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)) /2. Patients were grouped into group A and B based on their TyG Index with group A containing patients with TyG index less than 8.8 and group B containing patients with TyG index equal to or greater than 8.8. To measure the outcomes, the record was evaluated for mortality during the first 30 post-stroke days. Patients who survived the follow up record was retrieved and functional status was measured using modified Rankin Scale (mRS) and grouped as score no/slight disability (score 0-1), moderate disability (score 2-3), severe disability (score 4-5) and dead (score 6). Hospital stay (during index hospitalization) was measured by recording the time and date and admission and time and date of discharge from the hospital. The length of hospital stay was measured in days. Additional cardiovascular events like myocardial infarction or another episode of stroke during the follow up 3 months period were grouped into major adverse cardiovascular events.\n\nData was analyzed using statistical analysis program IBM SPSS version 25. Descriptive statistics was used to present the demographics and baseline clinical characteristics of the participants. Means ± SD was used for quantitative data while frequencies and percentages were recorded for qualitative data. Inferential statistics was applied to compare both groups for outcomes. Independent sample t test or Mann Whitney U test was used to compare quantitative data while qualitative data was compared using chi square or fisher exact test in univariate analysis. P value ≤0.05 was considered statistically significant. In multivariate analysis, binary logistic regression was used to assess the link between the TyG index and primary outcomes, confounding for age, gender, diabetes, and hypertension. Odds ratios (OR) with 95% CI assessed association strength. Odds ratio with 95% CI excluding 1 was considered statistically significant.\n\nThe IRB of Khyber Teaching Hospital, Peshawar accepted the research protocol. Approval was granted vide no: 47, dated: 26th July 2022. Research was retrospective, thus informed consent was waived off.\n\n\nResults\n\nThe research divided 200 ischemic stroke patients between two groups. Group A contained 112 patients and group B 88. Both group A and group B included 51.8% and 51.1% males, respectively (p = 0.92). Group B showed higher rates of diabetes (73.9% vs. 31.3%, p < 0.001), hypertension (72.7% vs. 53.6%, p < 0.01), and dyslipidemia (59.1% vs. 44.6%, p = 0.05) than Group A. Table 1 shows that the groups smoked similarly (p = 0.47).\n\nTable 2 shows demographics. The average age of participants in Group A was 65.4 ± 10.2 years, slightly lower than Group B (67.1 ± 11.5 years), but not statistically significant (p = 0.253). Age distribution across categories was similar across groups. Both groups had comparable average BMI (26.4 ± 3.7 vs. 27.1 ± 4.1, p = 0.195). Most patients lived in cities, and there was no difference in education, and career. Socioeconomic status was similar among both groups.\n\nTable 3 reveals no significant differences in duration of the disease (7.2 ± 4.8 years for Group A vs. 6.9 ± 5.1 years for Group B, p = 0.621), and drug consumption. Similar proportions of patients used anti-hypertensives, statins, anti-diabetics, anti-platelets, and anticoagulants, showing similar comorbidity treatment.\n\nTable 4 covers primary and secondary outcomes. Group B had a greater 30-day mortality rate (18.2% vs. 8.0%, p = 0.03) than Group A. A higher median (mRS) score at 3 months (3.5 vs. 2.5, p = 0.02) indicated poorer functional status in Group B. Patients in Group B had longer hospital stay (10.5 ± 3.1days vs. 8.2 ± 2.4days, p = 0.01) and higher rate of major adverse cardiovascular events (MACE) (15% vs. 7%, p = 0.05).\n\nTable 5 shows significant main outcome (30-day mortality) predictors using logistic regression. The adjusted odds ratio (OR) for 30-day mortality, 3-month mRS score, and stroke recurrence within one year was greater in Group B (OR = 2.5, 95% CI: 1.1-5.6, p = 0.03).\n\nTable 6 shows 3-month mRS score distribution. No symptoms or little disability were more common in Group A (mRS 0-1: 30.4% vs. 20.5%, p = 0.12) and substantial disability (mRS 2-3: 50% vs. 36.4%, p = 0.05). The percentage of seriously disabled patients in Group B was substantially larger (mRS 4-5: 34.1% vs. 13.4%, p = 0.002). The groups had comparable death rates (mRS 6) (p = 0.49).\n\n\nDiscussion\n\nThe study thoroughly compared socio-demographics and clinical parameters, in ischemic stroke patients with different TyG index values. The gender distribution in our study was evenly distributed throughout the groups with the proportion of male patients slightly higher than female, which aligns with prior study examining the correlation between metabolic indicators and stroke outcomes.10 However, our analysis revealed notable disparities in the occurrence of diabetes, hypertension, and dyslipidemia among the groups. These findings are consistent with research indicating that these additional health conditions are common among individuals who have had a stroke and can have an impact on the results or consequences.11 A research by Wang L and colleagues, revealed that diabetes patients with elevated TyG indices have a greater propensity to develop comorbidities such as hypertension and dyslipidemia which aligns with our research.12\n\nThe 30-day mortality rate in Group A (8%) considerably decreases than Group B (18%) (p = 0.03). This finding indicates that the intervention, and feature being studied in Group A might also have a beneficial effect in lowering short-term mortality compared to Group B. Several studies have reported findings similar to our research. A study by Mosisa et al. observed a similar mortality rate reduction in patients receiving similar interventions to Group A.13 Similarly, a study by Moraes et al, demonstrated a statistically sizable lower in 30-day mortality with a similar remedy approach.14\n\nConversely, research by Massaud and colleagues and Guo J et al, suggested lower mortality rates in patients with TyG more than 8.8 in comparison to Group B in our research.15,16 Variations in affected participants demographics, treatment protocols, and other factors could have an effect on mortality consequences different than observed in our research.\n\nThe median mRS score at three months was 2.5 in Group A and 3.5 in Group B, with a statistically great distinction (p = 0.02). This suggests higher functional consequences at 3 months among patients in Group A in comparison to Group B. Similar findings were mentioned by means of Chye et al, and De Silva et al., who found better mRS rankings at three months of their intervention groups as compared to controls.17,18 These studies support our finding that the intervention, and feature in Group A may additionally make contributions positively to functional recovery.\n\nStudies by Altuntas et al. and Ernst et al, specified no huge difference in mRS scores between intervention and control groups, differing from our effects.19,20 These discrepancies highlight the complexity in accomplishing constant results throughout studies, probably due to variations in research design, patient selection and treatment modalities.\n\nThe extended duration of hospitalization for patients in Group B (10.5 ± 3.1 days vs. 8.2 ± 2.4 days, p = 0.01) and the increased occurrence of Major Adverse Cardiovascular Events (MACE) (15% vs. 7%, p = 0.05) emphasize the added healthcare burden linked to elevated TyG indices. Research conducted by Li X et al, supports the claim that metabolic syndrome components, such as high levels of triglycerides and glucose, have a substantial effect on the length of hospital stay and the occurrence of cardiovascular problems in stroke patients.21\n\nThe logistic regression analysis indicated that an elevated TyG index is a standalone predictor of unfavourable outcomes. The results show that the TyG index has a significant predictive value, as evidenced by the adjusted odds ratios for 30-day mortality (OR = 2.5, 95%CI: 1.1-5.6, p = 0.03) and mRS score at 3 months (OR = 1.8, 95%CI: 1.2-3.0, p = 0.02). This discovery aligns with a research by Gao et al, which found comparable odds ratios for negative outcomes in patients with high TyG indices.22\n\nGroup B (TyG index >8.8) had a larger proportion of severe disability (mRS 4-5: 34.1% vs. 13.4%, p = 0.002) after 3 months, indicating that the higher TyG index significantly affected functional recovery. Prior research, such as the study conducted by Liu D and colleagues, has emphasized the connection between higher levels of triglycerides and glucose and unfavorable neurological outcomes, which supports our own findings.23\n\nThe TyG index may predict outcomes in diabetic ischemic stroke patients, according to one research.24 Regular triglyceride and glucose monitoring may help identify high-risk individuals who may benefit from more aggressive care to reduce unfavorable outcomes. Lifestyle adjustments and tailored medication may enhance prognosis in this patient group by lowering the TyG index.\n\nOur study was conducted at a single center, which may limit the findings’ applicability to larger groups. The sample size, while acceptable for statistical analysis, may not include all potential factors impacting outcomes. The TyG index, while a valuable measure, is generated using fasting glucose and triglyceride levels, which might fluctuate over time and may not fully reflect dynamic changes in metabolic status. While we focused on 30-day mortality and mRS scores at 3 months as key outcomes, other relevant clinical endpoints or patient-reported outcomes may give additional information about long-term prognosis and functional recovery.\n\nDespite these limitations, this research provides important insights into the relationship between the TyG index, metabolic markers, and clinical outcomes in patients with ischemic stroke. Future research should overcome these limitations by conducting prospective, multicenter studies with bigger sample sizes and more complete data collecting to validate our findings and gain a deeper understanding of the underlying mechanisms.\n\n\nConclusion\n\nThis research establishes a significant association among the TyG score and unfavorable outcomes in individuals with ischemic stroke. An elevated TyG index is associated with greater mortality and worse functional status indicating its potential as a helpful prognostic indicator. These results emphasize the significance of targeting insulin resistance in the treatment of ischemic stroke to enhance patient outcomes. Additional investigation is necessary to validate these findings and to create specific therapies aimed at decreasing insulin resistance in this particular group of patients.\n\n\nEthical considerations\n\nThe IRB of Khyber Teaching Hospital, Peshawar accepted the research protocol. Approval was granted vide no: 47, dated: 26th July 2022. Research was retrospective, thus informed consent was waived off. The institute granted the permission to share the data publicly.",
"appendix": "Data availability statement\n\nAuthor: Bibi, Chaand\n\nHarvard Dataverse\n\nAssociation of triglyceride-glucose index with outcomes of ischemic stroke\n\nDOI: 10.7910/DVN/4JJ8FA\n\nhttp://doi.org/10.7910/DVN/4JJ8FA\n\nThe project contains the following data:\n\n• SPSS.tab\n\nData is available under CC0 1.0 license\n\n\nReferences\n\nKatan M, Luft A: Global Burden of Stroke. Semin. Neurol. 2018; 38(2): 208–211. Publisher Full Text\n\nPrabhakaran S, Ruff I, Bernstein RA: Acute stroke intervention: a systematic review. JAMA. 2015; 313(14): 1451–1462. Publisher Full Text\n\nLu Z, Xiong Y, Feng X, et al.: Insulin resistance estimated by estimated glucose disposal rate predicts outcomes in acute ischemic stroke patients. Cardiovasc. Diabetol. 2023; 22(1): 225. PubMed Abstract | Publisher Full Text\n\nTao LC, Xu JN, Wang TT, et al.: Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations. Cardiovasc. Diabetol. 2022; 21(1): 68. PubMed Abstract | Publisher Full Text\n\nYin JL, Yang J, Song XJ, et al.: Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies. Cardiovasc. Diabetol. 2024; 23(1): 177. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang Q, Xiao S, Jiao X, et al.: The triglyceride-glucose index is a predictor for cardiovascular and all-cause mortality in CVD patients with diabetes or pre-diabetes: evidence from NHANES 2001-2018. Cardiovasc. Diabetol. 2023; 22(1): 279. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTai S, Fu L, Zhang N, et al.: Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes. Cardiovasc. Diabetol. 2022; 21(1): 161. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWon KB, Park EJ, Han D, et al.: Triglyceride glucose index is an independent predictor for the progression of coronary artery calcification in the absence of heavy coronary artery calcification at baseline. Cardiovasc. Diabetol. 2020; 19(1): 34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang J, Tang H, Wang X, et al.: Association of triglyceride-glucose index with early neurological deterioration events in patients with acute ischemic stroke. Diabetol. Metab. Syndr. 2023; 15(1): 112. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYe Y, Zhou Q, Dai W, et al.: Gender differences in metabolic syndrome and its components in southern china using a healthy lifestyle index: a cross-sectional study. BMC Public Health. 2023; 23(1): 686. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang YS, Kim HL, Kim SH, et al.: Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement. J. Lipid Atheroscler. 2023; 12(1): 12–22. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang L, Cong HL, Zhang JX, et al.: Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome. Cardiovasc. Diabetol. 2020; 19(1): 80. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMosisa W, Gezehagn Y, Kune G, et al.: Survival status and predictors of mortality among adult Stroke patients admitted to Jimma University Medical Center, South west Ethiopia: A retrospective Cohort study. Vasc. Health Risk Manag. 2023; 19: 527–541. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoraes MA, Jesus PAP, Muniz LS, et al.: Ischemic stroke mortality and time for hospital arrival: analysis of the first 90 days. Rev. Esc. Enferm. U.S.P. 2023; 57: e20220309. Publisher Full Text\n\nMassaud RM, Accorsi TAD, Massant CG, et al.: In-hospital stroke protocol outcomes before and after the implementation of neurological assessments by telemedicine: an observational case-control study. Front. Neurol. 2024; 15: 1303995. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuo J, Tian M, Li Y, et al.: Exploring clinical indicator variations in stroke patients with multiple risk factors: focus on hypertension and inflammatory reactions. Eur. J. Med. Res. 2024; 29(1): 81. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChye A, Hackett ML, Hankey GJ, et al.: Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings. J. Am. Heart Assoc. 2022; 11(16): e025425. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDe Silva DA, Narasimhalu K, Huang IW, et al.: Long-Term Post-Stroke Functional Outcomes: A Comparison of Diabetics and Nondiabetics. Cerebrovasc. Dis. Extra. 2022; 12(1): 7–13. PubMed Abstract | Publisher Full Text\n\nAltuntaş O, Taş S, Çetin A: An investigation of the factors that influence functional improvement in stroke rehabilitation. Turk. J. Med. Sci. 2021; 51(3): 1448–1454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nErnst M, Boers AMM, Forkert ND, et al.: Impact of Ischemic Lesion Location on the mRS Score in Patients with Ischemic Stroke: A Voxel-Based Approach. AJNR Am. J. Neuroradiol. 2018; 39(11): 1989–1994. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi X, Zhai Y, Zhao J, et al.: Impact of Metabolic Syndrome and It’s Components on Prognosis in Patients With Cardiovascular Diseases: A Meta-Analysis. Front. Cardiovasc. Med. 2021; 8: 704145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGao Q, Lin Y, Xu R, et al.: Positive association of triglyceride-glucose index with new-onset hypertension among adults: a national cohort study in China. Cardiovasc. Diabetol. 2023; 22(1): 58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu D, Yang K, Gu H, et al.: Predictive effect of triglyceride-glucose index on clinical events in patients with acute ischemic stroke and type 2 diabetes mellitus. Cardiovasc. Diabetol. 2022; 21(1): 280. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang Y, Huang X, Wang Y, et al.: The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis. Cardiovasc. Diabetol. 2023; 22(1): 2. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "355309",
"date": "23 Jan 2025",
"name": "Nurcennet Kaynak",
"expertise": [
"Reviewer Expertise Impaired glucose metabolism as a risk factor in stroke",
"epidemiological studies",
"meta-analyses"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this current work, the authors Bibi et al present a retrospective observational study, investigating the association between triglyceride glucose index and the outcomes of ischemic stroke during short-term follow-up of 3 months. The results indicate that patients who have a higher TyG index have a high risk of mortality and worse functional outcome compared to patients who do not. In summary, I believe this study provides valuable contribution to the descriptive analysis of stroke patients in a setting with limited resources. Overall, the article would benefit from a more detailed description of methodology and results. Please enclosed my comments on the sections:\nIntroduction:\nThe prognostic role of triglyceride glucose be stated carefully, as there are no clear recommendations for the use of this biomarker in cardiovascular disease. If there are any, they should be mentioned here. The authors should indicate clearly what has been and not has been investigated regarding the association between Tyg-Index and ischemic stroke. This part especially would benefit from improving the language as to avoid confusions. This section would especially benefit from improving the language for optimizing readability.\n\nMethods:\nThe information about have many patients were included should be moved to the results. It should be stated as to why patients with severe cardiopulmonary disease were excluded, and how this was defined. The authors should comment on the potential selection bias as to why some patients might have missing data and therefore excluded from the analysis. It should be stated clearly under what circumstances the TyG Index was measured (esp. the time point) Why was 8.8 chosen as a cut-off. Did the authors also consider performing the analysis with TyG as a continuous variable. How was functional outcome assessed? Based on telephone interviews? I believe there is quite a bit of repetition in the methods. This should be avoided. The authors should not define the analysis as descriptive if there is a research question investigating the association between a variable and the outcome. Why did the authors choose the confounding factors listed, what was the rationale?\nResults:\nWhat is disease duration? This should be defined in an understandable way. The authors may use a graph to depict the distribution of mrs instead of a table.\nDiscussion\nThe use of the term “intervention” is severely misleading. As this is an observational study, intervention should be avoided as a term. In this regard this section should be revised completely. The authors should be careful in stating that the patients would benefit from more aggressive care, as there are no current data on this.\nGeneral: The authors should provide the STROBE-Checklist.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1475
|
https://f1000research.com/articles/13-1474/v1
|
03 Dec 24
|
{
"type": "Brief Report",
"title": "Investigating the Role of MUC19 in Glioblastoma Multiforme: Genetic Alterations and Implications for Patient Survival and Therapeutic Targeting",
"authors": [
"Abdallah Arafah",
"Woo Rin Lee",
"Abdallah Arafah"
],
"abstract": "Abstract*\nBackground Glioblastoma multiforme (GBM) is the most aggressive and lethal form of brain cancer, and is characterized by rapid progression and poor patient survival. Genetic mutations play a significant role in cancer development and recurrence. This study investigated the role of Mucin 19 (MUC19), a member of the mucin family that has been implicated in cancer progression. We aimed to assess whether MUC19 mutations are associated with a worse prognosis in patients with GBM and explore its potential as a therapeutic target.\n\nMethods Data from 16 independent GBM patient datasets were retrieved from the cBioPortal for Cancer Genomics, comprising over 5,600 patients. These patients were categorized into two groups based on their survival status: living and deceased. Clinical attributes, including mutation frequencies and survival outcomes, were analyzed to identify significant genetic alterations in the deceased group. MUC19 is one of the most prominent mutations. To functionally investigate the role of MUC19, we conducted RNA interference (RNAi) experiments using A172 glioblastoma cells. Small interfering RNA (siRNA) specific to MUC19 (siMUC19) was used to knock down MUC19 expression, whereas the negative control group was treated with non-targeting siRNA. The effects on cell viability, proliferation, and MUC19 expression were also assessed.\n\nResults Our analysis identified 10 significantly mutated genes in deceased GBM patients, with MUC19 showing the most prominent association with poor outcome. siRNA-mediated knockdown of MUC19 resulted in a significant reduction in cell growth and viability compared to the control group, supporting its role in GBM progression.\n\nConclusion MUC19 plays a significant role in GBM progression, and its suppression leads to reduced tumor cell growth. These findings suggest that MUC19 may be a promising therapeutic target for improving outcomes in patients with GBM. Further research is needed to explore its potential in clinical settings.",
"keywords": [
"Glioblastoma multiforme",
"genetic mutation",
"MUC19",
"MUC17",
"MUC16",
"patient survival",
"siRNA",
"targeted therapy"
],
"content": "Introduction\n\nGlioblastoma multiforme (GBM) is the most aggressive and common primary malignant brain tumor, accounting for approximately 45-50% of such cases.1 GBM typically originates from astrocytes, star-shaped cells that form part of the brain’s supportive tissue.2 It is more prevalent in older males than females. Despite aggressive treatments, such as surgical resection, radiotherapy, and chemotherapy, patient prognosis remains poor, with only minimal improvements in survival rates.3 GBM most commonly arises in the cerebral cortex, but can also occur in other areas, such as the spinal cord.4 Understanding the genetic alterations that occur in glioblastoma, particularly in deceased patients, is vital for unraveling tumor behavior, resistance mechanisms, and patient outcomes.5\n\nMutations in genes such as Phosphatase And Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR) contribute to aggressive tumor progression and poor survival rates.6 For example, EGFR mutations are linked to shorter survival times, whereas loss of PTEN is associated with treatment resistance.7 These genetic insights are critical for the development of personalized treatment strategies.8 However, limited research has comprehensively analyzed the relationship between specific genetic alterations and survival outcomes in glioblastoma, a gap this study seeks to fill.9 One such gene of interest is MUC19, a mucin family gene that plays a significant role in producing protective mucous layers in epithelial cells.10 While MUC19 is primarily linked to diseases such as inflammatory bowel disease, recent studies have suggested its involvement in cancer, making it a key target for understanding glioblastoma pathogenesis and potential therapeutic interventions.11\n\nThis study aimed to comprehensively analyze the genetic mutations in patients with glioblastoma, focusing on deceased patients. By organizing and assessing 16 significant studies, we aimed to investigate the influence of these genetic changes on survival outcomes. This analysis will provide insights into critical genes linked to disease progression and mortality, with the aim of identifying potential therapeutic targets and improving prognosis prediction in glioblastoma patients.\n\n\nMethods\n\nThe cBioPortal for Cancer Genomics was used as the primary database to collect patient data and analyze survival outcomes.12 A total of 16 studies were organized, focusing on clinical data related to patient survival: Brain Lower Grade Glioma (TCGA, Firehose Legacy), Brain Lower Grade Glioma (TCGA, PanCancer Atlas), Diffuse Glioma (GLASS Consortium), Diffuse Glioma (GLASS Consortium, Nature 2019), Diffuse Glioma (MSK, Clin Cancer Res 2024), glioma (MSK, Clin Cancer Res 2019), glioma (MSK, Nature 2019), Low-Grade Gliomas (UCSF, Science 2014), Merged Cohort of LGG and GBM (TCGA, Cell 2016), Brain Tumor PDXs (Mayo Clinic, Clin Cancer Res 2020), glioblastoma (CPTAC, Cell 2021), glioblastoma (Columbia, Nat Med. 2019), glioblastoma (TCGA, Cell 2013), glioblastoma (TCGA, Nature 2008), Glioblastoma Multiforme (TCGA, Firehose Legacy), and Glioblastoma Multiforme (TCGA, PanCancer Atlas). The clinical tab was selected for analysis, and survival graphs were generated for the patient groups based on survival status (live and deceased groups). The p values associated with the survival curves were carefully evaluated to ensure the best accuracy. The survival data encompassed 2,444 patients in the living group and 3,226 patients in the deceased group.\n\nA172 glioblastoma cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Cat. No. 11965092) supplemented with 10% fetal bovine serum (FBS; Gibco, Cat. No. 16000044) and 1% penicillin-streptomycin (Gibco, Cat. No. 15140122). The cells were maintained in a humidified incubator at 37°C and 5% CO2. The medium was replenished every 2–3 days, and cells were passaged upon reaching 80–90% confluence.\n\nTransient knockdown of MUC19 was achieved using RNA (siRNA). The cells were seeded in 6-well plates (Corning, Cat. no. 3516) and grown to 70% confluence before transfection. MUC19-specific siRNA (Bioneer, Cat. No. 283463) and non-targeting control siRNA (NC) (Bioneer, Cat. no. SN-1001) were transfected into cells using Lipofectamine RNAimax (Invitrogen, Cat. No. 13778075) according to the manufacturer’s instructions. After a 6-hour incubation period, the transfection medium was replaced with fresh cell culture medium. Cells were harvested seven days post-transfection for subsequent assays.\n\nTotal RNA was extracted from cells using an AccuPrep® Universal RNA Extraction Kit (Bioneer, Cat. No. K-3141), according to the manufacturer’s instructions. RNA was quantified using a NanoDrop 2000 spectrophotometer (Thermo Scientific, Cat. No. ND-2000), and 1 μg RNA was reverse transcribed into complementary DNA (cDNA) using a High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Cat. No. 4368814). The resulting cDNA was used as a template for PCR amplification, using specific primers for the gene of interest. PCR amplification was performed using Taq polymerase (Takara, Cat. No. R001A) under the following cycling conditions: initial denaturation at 95°C for 5 min, followed by 35 cycles at 95°C for 30 s, annealing at 60°C for 30 s, and extension at 72°C for 30 s. The amplified products were separated by electrophoresis on a 1.5% agarose gel containing ethidium bromide, and visualized under UV light using a gel documentation system (Biorad, Cat. No. 170-8185). DNA ladder markers (New England Biolabs, Cat. No. N3232S) were used to determine the molecular weights of the PCR products, and band intensities were quantified using ImageJ software (NIH, version 1.53k).\n\nCell viability was assessed using a Luna-FL Automated Cell Counter (Cat. No. L20001). Cells were harvested, resuspended in phosphate-buffered saline (PBS; Thermo Fisher Scientific, Cat. No. 10010023) and stained with acridine orange/propidium iodide (AO/PI) staining solution (Logos Biosystems, Cat. No. F23001). Viable and non-viable cells were counted using a Luna-FL device, which provides accurate quantification based on fluorescence and bright-field imaging. Data from triplicate experiments were averaged and statistical analyses were performed to assess the impact of MUC19 knockdown on cell viability.\n\nStatistical analyses were performed to evaluate the significance of genetic alterations and their association with survival outcomes in patients with glioblastoma multiforme (GBM) patients. Survival curves were generated using the Kaplan-Meier method, and differences between groups (living and deceased) were assessed using the log-rank test. The mutation frequencies for the top genes were compared between groups using Fisher’s exact test. P-values were adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) correction to obtain q-values. A threshold of p < 0.05 and q < 0.05 was considered statistically significant. All analyses were performed using R software (version 4.1.2), and the results were visualized using appropriate plotting functions. For siRNA experiments, statistical significance between control and siMUC19-treated groups was determined using Student’s t-test, with a p-value of < 0.05 considered significant.\n\n\nResults\n\nThe top ten mutated genes were significantly enriched in the deceased group of patients with GBM ( Table 1). These genes, including PTEN, Aquaporin 7 Pseudogene 1 (AQP7P1), EGFR, MUC19, FSHD Region Gene 2 Family Member B (FRG2B), Mucin 17 (MUC17), Transmembrane Protein 191A (TMEM191A), Mucin 16 (MUC16), Rho Guanine Nucleotide Exchange Factor 33 (ARHGEF33), and NACHT And WD Repeat Domain Containing 2 (NWD2), had notably higher mutation rates in the deceased group than in the living group. The analysis highlights the cytoband locations, mutation rates, and statistical significance of the differences, measured through p-values and q-values. Three members of the mucin (MUC) gene family (MUC19, MUC17, and MUC16) were prominent, with MUC19 being the most significant gene in the group.\n\nThe patients were divided into a living group (n = 2,444) and a deceased group (n = 3226). This table identifies ten of the most significant mutated genes enriched in the deceased groups. The table also displays the gene’s cytobands, their rates in both deceased and living groups, their log2 ratio, their p-value, and their q-value. Phosphatase and tensin homolog (PTEN), Aquaporin 7 Pseudogene 1 (AQP7P1), Epidermal growth factor receptor (EGFR), Mucin 19 (MUC19), FSHD Region Gene 2 Family Member B (FRG2B), Mucin 17 (MUC17), Transmembrane Protein 191A (Pseudogene) (TMEM191A), Mucin 16 (MUC16), Rho Guanine Nucleotide Exchange Factor 33 (ARHGEF33), NACHT And WD Repeat Domain Containing 2 (NWD2) genes were identified to be enriched in the deceased groups. This table has been reproduced with permission from Ref. 22.\n\nThe effect of siRNA targeting MUC19 (siMUC19) on MUC19 expression levels and cell viability in A172 glioblastoma cells was analyzed ( Figure 1). The gel electrophoresis results showed two bands corresponding to MUC19 and GAPDH in the negative control (NC) and siMUC19-treated cells ( Figure 1A). After siRNA treatment, MUC19 expression in the siMUC19 group was significantly reduced compared with that in the control group. Quantitative analysis revealed that control cells showed significantly decreased cell viability ( Figure 1A).\n\n(A) Gel electrophoresis results showing MUC19 and GAPDH (control) expression in negative control (NC) and siMUC19-treated A172 cells seven days post-transfection. The siMUC19 group exhibits significantly reduced MUC19 expression compared to the control (p = 0.0029) (N = 3). (B) Quantitative analysis of cell viability after siMUC19 transfection. Representative microscopy images demonstrating decreased cell density in siMUC19-treated cells compared to the control group. The bar graph shows significantly lower MUC19 expression in the siMUC19 group compared to the control (p = 0.0336) (N = 3), Scale bar = 200 μm.\n\nThe normalized MUC19 expression levels in the siMUC19 group were significantly lower than those in the control group, and microscopic images further confirmed a decrease in cell density ( Figure 1B). siMUC19-treated cells exhibited visibly fewer cells than the control group, supporting the observation of reduced cell growth. Statistical analysis revealed a significant difference between the two groups, with a p-value of 0.0336 ( Figure 1B). These findings suggest that MUC19 plays a key role in glioblastoma cell growth, supporting the hypothesis that targeting MUC19 could be a potential therapeutic strategy.\n\n\nDiscussion\n\nThis study provides significant insights into the genetic alterations associated with glioblastoma multiforme (GBM) mortality and highlights potential therapeutic targets, mainly focusing on mucin genes. Our findings revealed important differences in mutation frequencies between deceased and living GBM patients, offering new perspectives on disease progression and potential treatment strategies.\n\nOur analysis identified ten key mutated genes that were significantly enriched in deceased GBM patients, suggesting their potential role in disease severity and mortality. These genes, including PTEN, EGFR, AQP7P1, and FRG2B, as well as three mucin genes (MUC19, MUC17, and MUC16), were selected based on their low q-values and p-values, indicating strong statistical significance. The diverse chromosomal locations of these genes and their higher presence in deceased individuals emphasize their possible involvement in critical biological processes that impact patient outcomes.\n\nThe identification of well-known cancer-associated genes, such as PTEN and EGFR, in our analysis, aligns with previous studies, reinforcing their importance in GBM pathogenesis.13 PTEN loss and EGFR amplification have been associated with poorer survival outcomes in patients with GBM, suggesting that personalized treatment strategies targeting these alterations could be more effective.14 PTEN, which is located on chromosome 10q23.31, regulates cell growth and division.15 Its mutation rate of 26.37% in deceased patients compared to 12.16% in living patients underscores its significance in GBM progression. EGFR, found on chromosome 7p11.2, is involved in the cell growth and survival pathways. Its amplification, observed in 20.41% of deceased patients versus 8.75% of living patients, further emphasizes its role in aggressive GBM phenotypes. AQP7P1, a gene encoding an integral membrane protein involved in water transport, showed a striking difference, with a 23.16% mutation rate in deceased patients compared to 0% in living patients.16 This finding suggests a potential novel role of this gene in GBM pathogenesis, which warrants further investigation.\n\nA novel aspect of our findings is the identification of three mucin genes (MUC19, MUC17, and MUC16) among the top mutated genes in deceased patients with GBM. Although these genes are traditionally associated with the formation of protective mucous barriers in various bodily systems, their involvement in cancer pathogenesis, particularly in GBM, is less understood.17 MUC19 emerged was the most significant mucin gene in our analysis, with a mutation rate of 4.55% in deceased patients compared with 0% in living patients. Our siRNA experiments targeting MUC19 demonstrated a significant reduction in cell viability in A172 glioblastoma cells, suggesting its potential role in tumor cell survival and proliferation. These results indicate that MUC19 may be a viable therapeutic target, with the potential for the future development of targeted therapies aimed at silencing MUC19 expression. MUC17, located on chromosome 7q22.1, had a mutation rate of 9.93% in deceased patients versus 2.68% in living patients. This gene is known to play a role in creating a mucous barrier that protects the digestive system lining.18 Its increased mutation rate in deceased GBM patients suggests a potential role in tumor progression, possibly through cell adhesion or signaling pathway alterations. MUC16, found on chromosome 19p13.2, exhibited a mutation rate of 17.19% in deceased patients compared with 8.14% in living patients. This gene forms protective barriers on epithelial surfaces and is involved in cellular adhesion and immune responses. The higher mutation rate in deceased GBM patients may indicate a role in immune evasion or altered cell-cell interactions in more aggressive tumors.19 The roles of MUC17 and MUC16 in GBM progression require further investigation. Their potential contributions to GBM pathogenesis may involve cell adhesion, signaling, and immune modulation mechanisms that are yet to be fully elucidated in the context of brain tumors.20\n\nAlthough our study provides valuable insights, it has several limitations that should be addressed in future research. Our reliance on data from deceased GBM patients may introduce bias as these patients likely have more aggressive tumor phenotypes. Future studies should include a more balanced cohort of patients at various disease stages to provide a more comprehensive understanding of the genetic alterations throughout GBM progression.21 Focusing on mutations in specific genes may overlook other potential factors such as epigenetic changes or microenvironmental influences, which could also significantly affect patient outcomes. A more comprehensive approach that incorporates these factors would provide a fuller picture of GBM progression and potentially reveal additional therapeutic targets. While our siRNA experiments provided evidence for the role of MUC19 in glioblastoma cell viability, further studies are needed to explore the exact mechanisms by which MUC19, MUC17, and MUC16 contribute to tumor progression.20\n\nThis study highlights the importance of genetic alterations, particularly in mucin genes, in GBM progression and mortality. These findings underscore the potential for developing personalized treatment strategies targeting MUC19, MUC17, and MUC16 in future therapeutic approaches. Although our results provide a promising foundation, further research is essential to validate these findings and explore new avenues for GBM treatment.\n\nThis study used publicly available clinical data obtained from the cBioPortal for Cancer Genomics, which was anonymized and de-identified to protect patient confidentiality. No direct involvement of human or animal participants was observed in this study. All experimental procedures involving cell cultures adhered to institutional guidelines and regulations regarding ethical conduct in the research. Specifically, A172 glioblastoma cell lines were approved under standard laboratory protocols, ensuring the proper handling and disposal of biological materials to minimize environmental or safety risks.",
"appendix": "Data availability\n\nFigshare: Data_A comparative analysis of mutated genes that are enriched in deceased patients from cBioPortal analysis.xlsx, https://doi.org/10.6084/m9.figshare.27190986.v1.\n\nThis project contains the following underlying data:\n\n• Data_A comparative analysis of mutated genes enriched in deceased patients from cBioPortal analysis.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe thank the members of IRIS LAB for supporting the wet lab experiments.\n\n\nReferences\n\nHanif F, Muzaffar K, Perveen K, et al.: Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac. J. Cancer Prev. 2017; 18(1): 3–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrandao M, Simon T, Critchley G, et al.: Astrocytes, the rising stars of the glioblastoma microenvironment. Glia. 2019; 67(5): 779–790. PubMed Abstract | Publisher Full Text\n\nObrador E, Moreno-Murciano P, Oriol-Caballo M, et al.: Glioblastoma therapy: Past, present and future. Int. J. Mol. Sci. 2024; 25(5). PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavis M: Glioblastoma: Overview of disease and treatment. Clin. J. Oncol. Nurs. 2016; 20(5 Suppl): S2–S8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarsi Z, Allahyari Fard N, N.: Identification of key genes and pathways in glioblastoma using bioinformatics analysis. Mol. Cell. Oncol. 2023; 10(1): 2246657. PubMed Abstract | Publisher Full Text | Free Full Text\n\nErira A, Velandia F, Penagos J, et al.: Differential regulation of the EGFR/PI3K/AKT/PTEN pathway between low- and high-grade gliomas. Brain Sci. 2021; 11(12). PubMed Abstract | Publisher Full Text | Free Full Text\n\nEze N, Lee J-W, Yang D-H, et al.: PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma. Oral Oncol. 2019; 91: 69–78. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang Y-F, Chiao M-T, Hsiao T-H, et al.: Genetic mutation patterns among glioblastoma patients in the Taiwanese population: insights from a single-institution retrospective study. Cancer Gene Ther. 2024; 31(6): 894–903. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHill C, Hunter SB, Brat DJ: Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. Adv. Anat. Pathol. 2003; 10(4): 212–217. PubMed Abstract | Publisher Full Text\n\nAdler KB, Tuvim MJ, Dickey BF: Regulated mucin secretion from airway epithelial cells. Front. Endocrinol (Lausanne). 2013; 4: 129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYu DF, Chen Y, Han JM, et al.: MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren syndrome patients. Exp. Eye Res. 2008; 86(2): 403–411. PubMed Abstract | Publisher Full Text\n\nGao J, Aksoy BA, Dogrusoz U, et al.: Integrative analysis of complex cancer genomics and clinical profiles using the CBioPortal. Sci. Signal. 2013; 6(269): pl1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmith JS, Tachibana I, Passe SM, et al.: PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J. Natl. Cancer Inst. 2001; 93(16): 1246–1256. Publisher Full Text\n\nEttl T, Baader K, Stiegler C, et al.: Loss of PTEN is associated with elevated EGFR and HER2 expression and poor prognosis in salivary gland cancer. Br. J. Cancer. 2012; 106(4): 719–726. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMolinari F, Frattini M: Functions and regulation of the PTEN gene in colorectal cancer. Front. Oncol. 2013; 3: 326. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTown M, Jean G, Cherqui S, et al.: A novel gene encoding an integral membrane protein has been mutated in nephropathic cystinosis. Nat. Genet. 1998; 18(4): 319–324. PubMed Abstract | Publisher Full Text\n\nSheng YH, Hasnain SZ, Mucins M: The underappreciated host defense system. Front. Cell. Infect. Microbiol. 2022; 12: 856962. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGum JR, Crawley SC, Hicks JW, et al.: MUC17, a novel membrane-tethered mucin. Biochem. Biophys. Res. Commun. 2002; 291(3): 466–475. PubMed Abstract | Publisher Full Text\n\nBlalock TD, Spurr-Michaud SJ, Tisdale AS, et al.: Functions of MUC16 in corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 2007; 48(10): 4509–4518. Publisher Full Text\n\nWi D-H, Cha J-H, Jung Y-S: Mucin in cancer: A stealth cloak for cancer cells. BMB Rep. 2021; 54(7): 344–355. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHaque A, Banik NL, Ray SK: Molecular alterations in glioblastoma: potential targets for immunotherapy. Prog. Mol. Biol. Transl. Sci. 2011; 98: 187–234. PubMed Abstract | Publisher Full Text | Free Full Text\n\nArafah A: The Prognostic Value of Copy Number Variations and Gene Mutations in Glioblastoma: Insights from a Large-Scale Bioinformatic Study. Int. J. High Sch. Res. 2024; 6(10): 61–65. Publisher Full Text"
}
|
[
{
"id": "345956",
"date": "13 Dec 2024",
"name": "Amna Makawi",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Gene ontology",
"Cancer",
"genetic diseases"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper was written in an organised way and it was easy to follow and understand what the author is trying to convey.\n\nGlioblastoma Multiform is a very aggressive tumour with a poor prognosis and any literature that can be provided on this tumour is important to provide insights on future therapeutic approaches. Here the author used cbioportal database and also did a wet lab experiment to highlight the role that MUC19 could play in patients with GBM.\n\nI would however suggest adding a separate conclusion section and clearly illustrate what can be concluded from the study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1474
|
https://f1000research.com/articles/13-1472/v1
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03 Dec 24
|
{
"type": "Research Article",
"title": "Influence of perceived congruence in basic moral values on perceived level of ethical leadership: A Russophone organization case",
"authors": [
"Alexey Belinskiy",
"Carl Olsen",
"Carl Olsen"
],
"abstract": "Background This study investigates the influence of perceived follower–leader congruence in basic moral behaviors, as defined by the morality-as-cooperation theory (MAC), on the perceived level of ethical leadership. Although important for the leadership theory and practice, this association is scarcely covered by the literature.\n\nMethods The study employed a mixed-methods approach, consisting of a one-site quantitative survey in Phase 1 carried out in a Russophone logistics company, and a follow-up series of semi-structured interviews within the same population in Phase 2.\n\nResults The results of Phase 1 showed a moderate positive correlation (r(54) = [.34;.64], p < .05) between perceived congruence in each MAC element and the perceived level of ethical leadership, whereas the findings from Phase 2 demonstrated that this association is causal. Moreover, the research unexpectedly revealed that the influence of the congruence in care for kin, heroism, and deference is mediated by the congruence in loyalty to the group and reciprocity, with the significance level at p < .05 for all indirect effects. The study also found a moderating role of duration of leader’s moral behavior observation by followers.\n\nConclusions This research advances ethical leadership literature by applying the MAC theory to studying the antecedents of the perceived leaders’ ethicality and revealing the mediating role of some basic moral values in assessing a leader’s ethicality. Besides, the study contributes to the cross-cultural validity of both MAC and ethical leadership theories by testing the respective instruments in a Russophone organization.",
"keywords": [
"ethical leadership",
"morality-as-cooperation",
"value congruence",
"moral values",
"moral behavior",
"perceived ethicality"
],
"content": "Introduction\n\nThe emphasis on ethical behavior in organizational circumstances and its specific relevance to leadership practice was fueled by corporate scandals at the beginning of this century (Hoch, Bommer, Dulebohn, & Wu, 2018; Northouse, 2019). However, researchers differ substantially on their understanding of what exactly should be considered as ethical or moral (Westra & Andrews, 2022). Despite the claim that no universal ethics for humanity exists due to the dependence of ethics on cultural contexts (Wong, 1984), the recent developments in evolutionary moral psychology have offered various accounts of the moral basics that underlie the whole variety of ethics and morality that emerge in various circumstances (Curry, 2016; DeScioli, 2016; Haidt & Joseph 2004; Rai & Fiske, 2011; Schein & Gray, 2018).\n\nRecent literature stresses the importance of knowledge about antecedents of followers’ perception of a leader as ethical, and points to the lack of empirical research in this field (Banks, Fischer, Gooty, & Stock, 2021; Brown & Treviño, 2014). Given that a positive influence of such a perception on the group’s outcomes has been covered by numerous papers (Bedi, Alpaslan, & Green, 2016), the knowledge of factors influencing the perceived level of ethical leadership turns out to be a valuable tool for ethical leaders aiming to enhance the outcomes.\n\nParaphrasing Edwards and Cable’s (2009) definition of values, personal moral values may be specified as general beliefs about morally acceptable and desirable behaviors or end states. Hayes, Pankey and Gregg (2002) argue that personal value congruence occurs when someone’s behavior corresponds with self-attributed values. This entails the importance of moral value congruence for ethical assessment of leaders’ behaviors. Banks et al. (2021) posit that the congruence of leaders’ behavioral signals, such as prosocial values, with their followers’ moral identities, which is defined by Wang and Hackett (2020) as sets of self-associated moral values, determines their evaluation as ethical or unethical. However, while the association of value congruence with ethical leadership has been addressed by recent publications, there is still a scarcity of empirical studies on this subject (Peng & Lin, 2017).\n\nMore specifically, few studies focus on follower–leader moral value congruence as a factor influencing followers’ ethical evaluation, including Egorov, Kalshoven, Pircher Verdorfer, and Peus (2020) and Pircher Verdorfer and Peus (2020), and neither provide empirical evidence of causality. This research aims to provide such evidence by a one-site mixed-method inquiry to the follower–leader congruence in moral values as a causal antecedent of followers’ moral evaluation of ethical leaders’ behaviors.\n\nMoral judgment on a leader’s behavior employs various criteria, either rational or irrational, and conscious or unconscious (Alfano, 2022; Haidt, 2012). Curry (2016) proposed the morality-as-cooperation (MAC) theory, which posits that morality represents a set of typical solutions for the cooperation problems that humanity has faced in our species’ history. Intra-group interactions and gene–culture co-evolution have led to the adoption of such solutions and their conceptualization as morally acceptable behaviors (Tomasello, 2016; Buchanan, 2020). Curry (2016) argues that they correspond to the cooperative games studied by game theory, which involve such behavioral strategies as care for kin, loyalty to the group, reciprocal exchange, dominance and heroism, deference and submission, fairness in dividing disputed resources, and respect to prior possession ( Table 1). These behaviors are thus widely considered moral (Curry, 2016), and turn out to be universally morally relevant to all cultures across the globe (Alfano, Cheong, & Curry, 2022; Curry, Mullins, & Whiterhouse, 2019b).\n\nAccording to Curry, Alfano, Brandt, and Pelican’s (2021) suggestion, the MAC basic moral behaviors, or MAC values, represent basic elements of human morality, that, taken in various combinations, can possibly constitute any known moral value. Assuming this hypothesis on morality as a combinatorial system as true, the appreciation of basic moral behaviors should be present in any moral assessment, and if a leader’s behavior demonstrates adherence to those basic moral elements, then it should be evaluated as ethical.\n\nSummarizing the above, Curry and his colleagues suggest that basic cooperative moral values represent the culturally universal basis of morality, in whatever values it may be explicitly expressed or implicitly perceived. Hence, the MAC basic moral values can serve as culturally universal criteria for moral evaluation of a leader. Therefore, the aim of this study is to explore whether congruence in MAC basic moral elements causally influences the evaluation of a leader as ethical, which, to the knowledge of the authors, has not been covered by empirical research so far.\n\nThe two main studies on cross-cultural universality of MAC values (Alfano et al., 2022; Curry, Mullins, & Whiterhouse, 2019b) were based on anthropological sources written in English. They noted this as a limitation, and thus suggested testing the MAC in various languages and cultural contexts as an avenue for further research. Russian-speaking organizations is one of such non-English cultural contexts, the application to which can provide a valuable contribution to the cross-cultural validity of the theory.\n\nThe Russophone diaspora is one of the world’s largest (Ryazantsev, 2015), which spreads beyond the post-Soviet area. In some Western countries such as the United States, Germany, and Israel, the Russophones have formed extensive well-established communities hundreds of thousands or millions strong that continue to use Russian for informal and formal business communications (Zabrodskaya & Ivanova, 2021). However, notwithstanding the topic’s importance, a literature search returns no studies on the MAC applied to the Russophone groups. Similarly, there is a scarcity of studies on ethical leadership in the Russophone cultural context. Therefore, the application of both these theories in a Russian-speaking organization was expected to offer important contributions to both fields.\n\nTherefore, to close the gap identified above, the following research question (RQ) has been posed: Does the perceived follower–leader congruence in MAC basic moral elements causally influence the perceived level of ethical leadership in the Russophone language context?\n\n\nMethod\n\nThe expected answer to the RQ depends on the results of testing for two research hypotheses. First, the association hypothesis RH1: The relationship between perceived follower–leader congruence in any of the MAC elements (Xn) and perceived level of ethical leadership (Y) is statistically significant. If confirmed, the causality hypothesis RH2 should be tested: The influence of perceived follower–leader congruence in any of the MAC elements on the perceived level of ethical leadership (Xn→Y) is causal. The conceptual model is depicted in Figure 1.\n\nThe figure depicts the conceptual framework to be tested on association and causality. Hn stand for hypotheses alternative to the null hypotheses outlined in Table 9. a Each Xn signifies perceived congruence in respective MAC elements drawn from Curry (2016). b Y stands for perceived ethical leadership construct suggested by Brown, Treviño, and Harrison (2005).\n\nDiscussing the methodological issues of causal inference in empirical research, Maxwell (2004) advocates a realist approach, which recognizes the validity of both positivist and interpretivist methods, and suggests ways of allowing for causality inference in a single-setting design, such as, for example, triangulation of quantitative and comparative qualitative data. Thus, this research was structured as a two-phase mixed-method study: the quantitative cross-sectional testing of the relationships’ significance and differences in means, and the follow-up qualitative cross-sectional inquiry into causality of findings from the first phase.\n\nAs the cross-sectional design was chosen due to the limited time frame for sampling provided by the sampled company, a survey with a subsequent quantitative analysis was conducted for testing RH1. Given the limited accuracy of possible causality inferences in a quantitative cross-sectional inquiry, a follow-up qualitative study is required for the exploration of causal relationships stated by RH2 (Gelfand, Mensinger, & Tenhave, 2009; MacKinnon, Fairchild, & Fritz, 2007). Thus, as a Phase 2, a series of semi-structured interviews were performed.\n\nFor Quantitative Phase 1, the study addressed confidentiality and anonymity by obtaining informed consent from all participants. Participants consented by checking a relevant box in the web form prior to starting answering questions. The consent was recorded and documented as per ethical guidelines. No data that could identify specific participants was collected, and the company received results only in aggregated form to ensure that individual identities were protected. The consent procedure and data handling process received prior approval from the SBS Swiss Business School Ethical Committee, in compliance with the Declaration of Helsinki’s principles. The date of approval is September 2, 2022, while the data collection was performed between 16 and 19 of September, 2022.\n\nFor Qualitative Phase 2, participants provided written consent, confirmed orally at the beginning of each interview. Data were anonymized personally by the researchers, and only anonymized data were used in the report. To ensure the company did not incur any damage and to maintain transparency, the approval of the CEO and HR Director was obtained before engaging with any employees. The results were presented to the company in an aggregated format, so that participants’ identities cannot be revealed in any circumstances. The procedures and the use of consent were reviewed and approved by the SBS Swiss Business School Ethical Committee. The date of approval is December 7, 2022, while the data collection spanned from 07 till 26 of December 2022.\n\nNo material incentive was offered or provided to any participant. All participants were informed of the study’s purpose, methods, and potential risks and benefits. They were made aware that participation was voluntary, and they could withdraw at any time without any consequences.\n\nAll data collected during this study were handled confidentially and stored securely on encrypted password-protected hard-disk of the researcher’s computer, and will be retained for five years before being destroyed.\n\nThis process ensured adherence to the principles of autonomy and respect for participants as stated in the Declaration of Helsinki.\n\n\nPhase 1: Method and procedures\n\nThe questionnaire was composed of items used in previous research. Two relevant instruments, presented below in detail, were drawn from the literature.\n\nFor the measurement of the seven basic moral behaviors suggested by MAC theory, Curry, Chesters, and Van Lissa (2019a) designed and validated the 42-item Morality-as-Cooperation Questionnaire (MAC-Q). Whereas MAC-Q measures perceived values themselves, the present research is aimed to measure perceived congruence on these values. Thus, the instrument’s introductory messages were modified in order to measure followers’ perceived congruence in basic moral elements with those of the leader’s, while the items themselves were left identical to those from the original questionnaire.\n\nThe literature suggests numerous approaches to measuring ethical leadership, which vary depending on the philosophical angle on ethics, focal respondents, and differences in the construct aspects that are intended to be measured (see for example Langlois, Lapointe, Valois, & de Leeuw, 2014; Kalshoven, Den Hartog, & De Hoogh, 2011; Riggio, Zhu, Reina, & Maroosis, 2010; Spangenberg & Theron, 2005; Yukl, Mahsud, Hassan, & Prussia, 2013). The majority of those instruments are in line with Brown et al.’s (2005) approach in assessing ethical leadership as a specific behavioral practice, though enhancing it in certain aspects. Meanwhile, the Ethical Leadership Scale (ELS) suggested by Brown and colleagues represents one of the most frequently used in empirical research of ethical leadership (Bedi et al., 2016). For this reason, this study considers the ELS as the most appropriate instrument for the empirical advancement of Brown et al.’s (2005) conceptualization of ethical leadership.\n\nThe questionnaire employed in the survey was therefore composed of two instruments: the ELS and the modified versions of the MAC-Q Relevance and Judgment scales, denoted as mMAC-Q(R) and mMAC-Q(J) scales in this study ( Table 2). Besides this, such demographic variables as gender, age and organizational level were collected in order to test between-group differences in responses. All non-demographic questionnaire’s items were measured using a 5-point Likert-type response range. Although numerous papers insist on better reliability of 7-point scales compared to 5-point scales (see for review Taherdoost, 2019), some others argue that the difference in reliability is insufficient, and 5-point scales are less confusing and easier to respond (Aybek & Toraman, 2022; Babakus & Mangold, 1992). Using this assumption, this research employed 5-point scale to be easier to read and understand from mobile screens by respondents, thereby helping them to avoid being overwhelmed when picking answers, which can more probably occur with a wider response scale.\n\na Names within quotation marks are drawn from Curry (2016).\n\nb The term is drawn from Brown et al. (2005).\n\nThe composed questionnaire was translated into Russian. The correctness of the items’ translation was checked by reverse-translation involving third-party translators. Then, a review of the instrument’s form and content was carried out by running a questionnaire among a private Russian HR community in order to ensure that the overall composition of the questionnaire was easy to use, the Russian wording of the items was clear to the respondents, and there was no misperception of the constructs which were supposed to be measured. After final wording amendments, the resulting instrument was exhibited at Google Forms platform for sampling.\n\nThe survey was conducted in a Russian logistics company (hereinafter the company). The total number of employees is 1319 located in various regions of Russia, among which 263 work in the Moscow headquarters, which was chosen as a sampling site following the company’s management requirements. However, although the behavioral patterns of the regional branches’ employees theoretically may differ from those of the Moscow HQ due to possible cultural differences between different regions of Russia, this limitation was considered negligible for the generalization of the results to the whole company, and wider to the people employed in the industrial sector of the Russian economy, as the substantial part of headquarters’ employees moved to Moscow from various regions and industries, according to the company’s management statement. No respondents were deliberately chosen for the participation by management or the researcher, and the entire process was voluntary and open to any participant. To that extent, the selection was random, although the choice of the company and its headquarters utilized convenience sampling.\n\nThe emails contained an introductory message motivating employees to participate in the survey were sent to all HQ employees, and provided a link to the questionnaire’s web-form. Confidentiality and anonymity issues were addressed thoroughly, as outlined below in the Ethics and Consent section.\n\nFifty six responses were received (Belinskiy & Olsen, 2024). The response rate was therefore 56/263, or 21 percent. Participation was voluntary, responses were anonymous, and there were no repetitive patterns of answers on any scales. Therefore, all responses (n = 56) were considered to have been made sincerely and consciously, and thus valid. Following Fritz and MacKinnon’s (2007) recommendations, a minimal required sample size should not be less 33 for valid regression analysis, so the actual sample size (n = 56) was found sufficient.\n\nThe amendment of the original MAC-Q in introductory messages changed the constructs being measured, and hence the validity of the instrument had to be verified. The initial measurement model was tested for a model fit using SPSS Amos 29 package in order to assess whether it fitted the dataset and was good in predictive capacity. CFA initially resulted in poor fit of all models combined from the MAC-Q items ( Table 3), in contrast to good fit demonstrated by the initial MAC-Q Relevance and Judgment scales (Curry, Chesters, & Van Lissa, 2019a). After removal of lower-loading factors and factors demonstrating the most salient levels of standardized residual covariance with those of other items, the best model fit was achieved when each of seven MAC constructs had been reduced to two items from the Relevance scale ( Figure 2): All factor loadings were above .70 and all model-fit values (CMIN Sig. .156, CFI .985, TLI .975, RMSEA .059, RMSEA 90%CI [.000, .107], PCLOSE .380) are close to levels commonly accepted in the literature as good-fit measures (Schreiber, Nora, Stage, Barlow, & King, 2006; Ullman, 2006); only the upper bound of RMSEA CI .107 exceeds Schreiber et al.’s threshold .08 ( Table 4). This model (hereinafter Model A’, mMAC-Q, or the MAC section of the instrument), was employed for the following reliability and validity analysis.\n\na Good fit reference values drawn from Schreiber et al. (2006), and Ullman (2006).\n\nThe figure represents the structural equation model for the best fitting model A’. It is generated using IBM SPSS Amos 29 software when performing CFA. Circles “X1” – “X7” represent latent variables standing for basic moral behaviors (Curry, 2016). Squares like “rk3” represent observed variables correspondent to the respective questionnaire items ( Table 2). Ellipses denoted like “e3” represent errors, or the variance in the observed variable that is not explained by the latent variable.\n\nThe single-headed arrows indicate regression weights or factor loadings from one variable to another. The double-headed arrows represent correlations or covariances between latent variables. The numbers next to these arrows show the correlation values between different latent variables.\n\na Reference values drawn from Schreiber et al. (2006), and Ullman (2006).\n\nEach scale showed a Cronbach’s alpha within a range between .83 and .90, which represents a good level of internal consistency according to Taber’s (2018) review. The composite reliability value for each scale ranged from .83 to .91, exceeding the .70 threshold suggested by Hair, Ortinau, and Harrison (2010). Therefore, each construct in the reduced model was found reliable.\n\nPairwise correlations within each construct are positive and statistically significant (r > .70, p < .001) for all Xn1–Xn2 within-construct pairs ( Table 5). Each scale’s average variance-extracted value (AVE) exceeds the threshold .50 ( Table 6) suggested by Fornell and Larcker (1981). Thus, the scales of the reduced instrument demonstrate sufficient convergent validity.\n\na Intra-construct correlation.\n\nThe discriminant validity was assessed according to Fornell and Larcker’s (1981) criterion, implying that the square root of the scale’s AVE should exceed its correlation with other items in the model. This criterion was met for all items except the second item in “loyalty to the group” scale, which returned slightly negative differences between AVE square root and correlations with first and second items in “reciprocity” scale: -.02 and -.01 respectively ( Table 7).\n\na Satisfactory HTMT test.\n\nTherefore, the modified MAC-Q Relevance scale reduced to two items per each MAC-related construct, or mMAC-Q, was considered a valid instrument for measuring follower–leader perceived congruence in MAC elements. All data related to skipped or removed items was not taken into account in further analysis. Therefore, while the unchanged MAC-Q section of the instrument failed to demonstrate good model fit, the modified mMAC-Q section represents a valid and coherent model for measuring perceived congruence in MAC elements in Russian.\n\nSimilarly to the mMAC-Q section, the ELS scale demonstrated a high rate of internal consistency (α = .92). The EFA and CFA analyses confirmed Brown et al.’s (2005) argument that perceived ethical leadership measured by the 10-item ELS represents a coherent construct. The EFA returned a one-factor model with an eigenvalue of 5.96, so that 59.6 percent of variance is explained by one factor with the factor loading ranged from .483 to .894 per item. The CFA returned good model fit for the scale (CMIN Sig .326, CFI .990, TLI .987, RMSEA .041, RMSEA 90%CI [.000, .108], PCLOSE .538); hence, the original Brown et al.’s (2005) ELS was employed for further inferential analysis as a uni-dimensional measure of the Y variable.\n\nThe content validity of the Russian-worded items was qualitatively addressed in Phase 2, resulting in support for claims of Curry, Chesters, and Van Lissa (2019a) and Brown et al. (2005). Hence, the instrument is viewed as a valid instrument to measure the perceived level of ethical leadership in Russian-language contexts.\n\n\nPhase 1: Results\n\nAmong 56 responses, 34 participants were female and 22 were male. All the participants were adults, eight of them between 18 and 30 years old, 40 between 31 and 45, and the remaining eight within the 46 and 60 age range. A total of 18 responses were collected from those who received link one, 14 followed link two, and 24 received link three, which implies each response allocated to the corresponding organizational layer ( Table 8).\n\nRaw Likert integer values were transformed to continuous values by calculating the mean of the array of values corresponding to each scale of the instrument, thus forming the data-set for the statistical tests. Initial responses were coded as follows: strictly negative responses were coded as 1, strictly positive as 5, with a neutral point at 3. The means above 3, therefore, demonstrate the evidence of the perceived congruence in MAC elements in the case of independent variables, and perceived ethical leadership in the case of dependent one. The results demonstrate the perception of all MAC elements as congruent with the leader (3.31 < M < 3.89), and perception of the leadership as ethical (M = 3.86). The data were considered as normally distributed with skewness [-.10, .53] and excess kurtosis [-1.35, .75] intervals close to those proposed by Gravetter, Wallnau, Forzano, and Witnauer (2020) for normal distributions ( Table 8).\n\nSeven null hypotheses were posed for the quantitative test ( Table 9). The results demonstrated that all means of follower–leader perceived congruence, in each MAC element, correlate with perceived ethical leadership, with Pearson r(54) values ranging from .34 to .59 and significance level at p < .001, except those for “fairness” and “property” scales, which are significant at p < .05 and < .01 respectively ( Table 10). Regression analyses stress the argument for the rejection of all null hypotheses ( Table 11). Thus, the results were considered to show a statistically significant moderate positive linear correlation for each Xn–Y pair using Ratner’s (2009) criteria, which supports the RH1, meaning that there is a statistically significant relationship between perceived follower–leader congruence in each MAC element and the perceived level of ethical leadership ( Table 22).\n\nIt was expected that this association may be demographic sensitive, which means that age, gender, or organizational level may interfere between congruence in some MAC values and the perceived level of ethical leadership. To control for demographics, the difference in means between various population groups was assessed. However, tests for the equality of means between gender ( Table 12) and age ( Table 14) groups failed to demonstrate statistically significant differences between means of these groups ( Table 13; Table 15).\n\nIn comparison, a one-way ANOVA demonstrated that the difference in means between the top-management team (n = 18), middle management (n = 14), and lower-level staff (n = 24) is statistically significant for any variable at p < .001 ( Table 16; Table 17). A post-hoc pairwise Tukey HSD test showed that each variable demonstrated difference in means between top-management and two other organizational levels at least at p < .01 in all cases, except the difference in congruence in “fairness” significant at p = .021 ( Table 18). Meanwhile, neither comparison of variable means between mid- and lower-layers provided sufficient evidence of such a difference (p > 0.05). The mean differences between top-management and two other groups were all positive and fell into the range between .61 and 1.29, which signifies that each variable demonstrated a higher mean rate when assessed by top managers than when assessed by employees from other organizational layers.\n\n* The mean difference is significant at the 0.05 level.\n\nThis was assumed as a sign of possible moderation by the organizational layer parameter, and tested by a follow-up multiple regression ( Table 19). Baron and Kenny (1986) recommended comparing the unstandardized B for two scenarios: with and without the influence of a potential moderator. The test showed that adding an organizational layer as a moderator lowers levels of B in all seven Xn–Y relationships. Hence, the data quantitatively supported a moderating effect of the organizational layer. However, as shown below, the results from Phase 2 demonstrate that it is not the actual moderator, thought the moderation effect remains valid with another parameter.\n\nThe positive correlation itself does not entail the causality of Xn→Y. To be supported, the relationship should fulfill three conditions, namely (1) a significant association between variables, (2) a directional or temporal precedence of variance in Xn to variance in Y, and (3) an unconfoundedness of this relationship (Gelfand et al., 2009; Kenny, 1979). While the first condition is met, as reported above, the second is impossible to establish quantitatively in a cross-sectional design (Gelfand et al., 2009; MacKinnon et al., 2007), so it has been examined qualitatively in Phase 2, as recommended by Maxwell (2004). The third condition, unconfoundedness, appears to be the most questionable, as shown below.\n\nWhen planning the research, it was hypothesized (RH2) that each perceived congruence in MAC value causally impacts the perceived level of ethical leadership, and no possible interplay or interdependence of independent variables was assumed. The data show that all Xn–Xm pairwise correlations are significant and positive (.21 < r < .92, n = 56, p < .05), except for the pairs “property”–“group” and “property”–“reciprocity” which correlate at an insignificant p > .05 ( Table 20). This may signal that some XM variables might confound or mediate relationships of other Xn variables with Y.\n\nAccording to Kenny (1979), the unconfoundedness of the Xn–Y association implies that there is no controlling variable that turns their correlation insufficient or insignificant. Partial correlation test of Xn–Y associations controlled by any other XC variable returned insignificant (p > .05) partial correlations for 18 Xn–Y pairs out of 42 possible ( Table 21). The congruence in “kin”, “group”, “reciprocity” and “heroism” impacts some other constructs’ relationships with “perceived EL”, so that the unconfoundedness condition in this respect may not be fulfilled, hence questioning RH2. However, the quantitative data without theoretical explanation are not sufficient to infer a confounding influence (Pieters, 2017). Therefore, the qualitative inquiry was expected to reveal these variables’ capacity to determine the importance of congruence in other values for the perception of a leader as ethical, which is reported below.\n\n\nPhase 2: Method and procedures\n\nThe qualitative Phase 2 was intentionally limited in scope and focused only on themes which could confirm or reject the quantitative findings of the preceding survey. It aimed to triangulate the quantitative phase results by revealing qualitative evidence supporting or questioning RH2 to test whether two remaining conditions of causality are fulfilled, namely directionality and unconfoundedness. In addition, Phase 2 was aimed at verifying the Phase 1 assumption on the content validity of the Russian wording of the final instrument items.\n\nAccording to Maxwell (2004), a comparative multicase design represents a qualitative strategy allowing for causality testing of relationships. He argues that such an approach addresses concerns related to qualitative case studies inability to infer what would have happened if a presumed cause was not present (Cook, Campbell, & Shadish, 2002). Comparing cases here was expected to provide various perspectives on predetermined themes, so as to smooth the impact of one personal opinion on central tendency estimation. Hence, this phase represents the deductive case study, which is explanatory in Yin’ (2013) terminology, or instrumental in the Stake’s (1995) one, conducted in a multiple-case design for examination of causality following Maxwell’s (2004) recommendations, meaning by multiple cases the interviews made in a single organizational context.\n\nSemi-structured interviews were chosen as a methodology for Phase 2 to ensure the collection of comparable statements or judgments by setting particular themes for discussion. The propositions, a term suggested by Yin (2013), are based on the MAC (Curry, 2016) and ethical leadership (Brown et al., 2005) theories, as well as the findings of Phase 1. The following questions were therefore posed for qualitative inquiry. First, have the relevant phenomena been properly measured by the items employed by Phase 1? The answer requires a qualitative examination of the relevance of the Russian wording of the mMAC-Q and the ELS sections’ items to the domain of perceived leaders’ morality, or the content validity of the questionnaire’s items. Second, are these constructs and the conceptual model relevant to the organizational context of the company? This implies examining whether the congruence in MAC values influences and precedes the perceived ethicality of the leader, how some MAC values interfere with others in their influence on the latter, and whether such an influence is unilateral and causal.\n\nThe literature suggests that the most common principle for defining the adequate sample size is saturation, which represents the point when the additional data reveals no new properties or insights about a construct examined (Guest, Bunce, & Johnson, 2006). Hennink and Kaiser (2022) show that, in recent empirical studies, the saturation was typically achieved within a range from 9 to 17 interviews, with a mean at 12–13 interviews, if the population was homogeneous, and objects were narrowly defined. Since Phase 2 involved sampling from a culturally homogeneous one-site population, and examined relationships between constructs that were narrowly defined by previous research, the sample size was arbitrarily set at 14 interviews. Applying the Hennink, Kaiser, and Marconi’s (2017) criteria, the code saturation was achieved after coding the first three interviews, while the meaning saturation was reached after the coding of the 10th interview, when no new meanings, nuances, or insights were found by analyzing the remaining transcripts. Therefore, 14 interviews were eventually considered the adequate sample size, which provided the necessary richness and depth of the qualitative data.\n\nCandidates for interviews were selected in collaboration with the company’s HR director based on the following criteria: they worked in the HQ of the company, they did not participate in the Phase 1 survey, and they demonstrated an interest in participation. The HR director had a series of phone conversations with potential participants until seven top-level and seven lower-level candidates had agreed to participate ( Table 23).\n\nFor the avoidance of researcher bias, a professional Russian-speaking interviewer was invited to perform all interviews. Her purpose was to motivate interviewees to talk freely about themes taken from the modified instrument and provide justifications or rationalizations for their judgments and evaluations. In addition to this, she was expected to discuss with the participants what would happen to their perception of a leader if a similarity in moral values were to change. Practically, interviewees were asked to express their thoughts about the items used in the preceding survey.\n\nThere were six female and eight male participants. All conversations were conducted and transcribed verbatim in Russian, which was the mother tongue of the majority of the interviewees. Those two persons who noted that their mother tongue was not Russian, spoke Russian with nativelike proficiency. The series of 14 interviews resulted in 1053 minutes of records, with each interview’s length lying in the range [57 min, 95 min], mean 75 minutes ( Table 23). Transcript files exceeded 120,000 words in total volume.\n\nThe set of verified transcripts was analyzed applying Braun and Clarke’s (2006) six-phase framework for thematic analysis using the Nvivo 1.7 package. The data and propositions were linked by the markers of assertion and explanation. When a phenomenon was named relevant or important, it was coded correspondingly. When the explanation of that importance indicated other markers of the importance, they were also linked to the respective proposition as potentially influencing the phenomenon they were used to explain. The main criterion of the relevance of evidence found in the data was frequency of display across numerous cases. When some aspect was found as coded episodically, it was eventually neglected; only assertion or explanation patterns that were widely repeated in numerous interviews were considered to reflect a tendency in the given population.\n\nAfter the initial coding, the codes were collated into themes, a term which here denotes data units for further interpretation of the aspects of phenomena under examination (Boyatzis, 1998). The final iteration of review of transcripts, codes, and themes and elimination of the episodically mentioned codes and themes resulted in a final theme list. It needs to be noted that the coding was performed by the researcher, so the consideration of results of Phase 2 should keep in mind potential researcher bias, though the data analysis has been attempted in good faith, without conscious intention to confirm the findings of the previous phase.\n\nEthical issues were addressed adhering to the Declaration of Helsinki principles, as outlined in detail in Ethics and Consent section below.\n\n\nPhase 2: Results\n\nEach interview in Phase 2 included discussion about every item of the ELS in order to confirm the validity of Brown et al.’s (2005) interpretation of the ethical leadership concept for the company, which operates in a Russian cultural context within a specific industrial subculture. The way the content was coded resulted in numerous quotes referencing the ELS items’ relevance ( Table 24). All interviewees expressed no doubt when evaluating their CEO as an ethical leader, and that their judgments were unequivocal and unconditional. Despite the fact that four out of 10 items of ELS were considered as irrelevant by some interviewees, the dominant sentiment is that all aspects are important for such an evaluation. Hence, the present study confirms the content validity of the Russian-language ELS instrument when applied to the sample company.\n\nThere was no difference found between top- and lower-level interviewees in evaluation of their CEO as an ethical leader. All of them unequivocally assessed the leader as ethical, and all expressed sympathy and general follower-leader congruence in moral values. At the same time, the majority of participants noted a difference between top managers and other employees in evaluation of the leader. This is consistent with the moderating role of the organizational layer parameter revealed in Phase 1, though the data demonstrate its derivative nature.\n\nIn responses to the reasoning request, interviewees explained the difference with reference to a proximity to the leader. At the same time, they repeatedly pointed out that proximity to the leader is not sufficient when communication is lacking. Communication frequency was noted by the interviewees as an even more important parameter influencing the evaluation of the leader as ethical. Direct communication was mentioned as an instrument for shaping followers’ perception, and thus one of the main constraints in big companies. Hence, communication deficit turns out to be the main reason for the difference between organizational levels in perceived level of ethical leadership. When communication is sufficient, the difference may disappear. None of the interviews pointed to a different reason.\n\nTherefore, although the perceived level of ethical leadership depends on the organizational level of evaluators in the focal population, the moderating role of the organizational layer parameter revealed in Phase 1 is found to be company specific, and not generalizable to a wider population. Instead, the leader’s proximity, that is behavioral visibility and cumulative communication duration with followers, emerge as factors influencing the perceived level of ethical leadership.\n\nSimilarly, there is a difference in moral value congruence between different organizational levels and the leader. The proximity and communication were also noted as main reasons. On the other hand, inability to understand the leader was pointed out as a reason for the difference in value congruence. Hence, the farther the hierarchical distance between the leader and his actual or potential followers, the less their capacity for interaction, and, thus, the bigger the gap in congruence.\n\nWhile the data set contains multiple indication of the perceived link between moral value congruence and the perception of ethical leadership, the exact mention of directionality is essential for the establishment or refutation of a causality hypothesis, namely the explicit indication that change in perceived value congruence precedes the change in the perceived level of ethical leadership or, vice versa—the mention of the influence of ethical leadership on moral value congruence.\n\nAlthough there is some mentioning of a congruence itself as a factor influencing ethical leadership, the main body of evidence is centered around the relevance of MAC moral behaviors for the assessment of a leader as ethical. The interviewees were responding to questions about the importance of these moral behaviors in such an evaluation, and, when justifying their opinions, they were predominantly talking about what is important for them personally, which was treated as possessing focal value or indicating appreciation of the corresponding behavior. Therefore, the relevance discussion was understood as a discussion about implied value congruence between participants and either an ideal leader of their dreams or the actual leader of the company.\n\nAll MAC basic behaviors were recognized as important for the evaluation of a leader as ethical ( Table 25), though with differences in some nuances.\n\nCare for kin (“kin”, X1) was mainly pointed out as important for a leader mostly in the context of a group. Interviewees perceived such care as proof that their expectations regarding the leader’s care for a group would also be fulfilled. Although some point to a low significance of care for kin for leadership, such a view is rarely represented in the dataset.\n\nThe importance of loyalty to the group and care for its members (“group”, X2) is supported unanimously. All reasoning going beyond the intrinsic importance of a group itself is centered on performance indicators and factors leading to a better productivity. Uniting people within a group is seen as a prerequisite for productive work. This is consistent with group dynamics theorists positing that group cannot exist without cohesiveness (Dion, 2000). Hence, care for a group turns out to be a core value, as it directly impacts the group’s well-being, while, on the contrary, lack of care entails lack of confidence.\n\nSuch a confidence is a main rationale expressed by the interviewees when discussing the importance of a leader’s being reciprocal (“reciprocity”, X3), which is perceived in terms of predictability. Reciprocal behavior is noted to be a facilitator of performance, and, thus, all participants are unanimous in feeling that the promises should be fulfilled. Hence, the consistency in reciprocity is stated as a basis of trust. Some perceive a leader with trust in advance, but a low level of reciprocity, when observed frequently, leads to the decrease in overall trust level.\n\nHawkish (“heroism”, X4) and dove-ish (“deference”, X5) behaviors are mentioned by the MAC as a conflict-avoidance strategy and are both regarded as valuable in the leadership context. Being assertive and bold was regarded as a positive trait by all interviewees, as they recognize a leader’s responsibility to drive the company. It was noted that such behavior is inevitable if a leader aims to keep the big organization manageable. Participant 8 placed the importance of the ability to make hard decisions in the context of reciprocity, as making them entails making alike decisions by team members. Domination has also been mentioned as a productive behavioral feature in terms of day-to-day management.\n\nDeference was a regarded feature as well, however. Talking about a leader in a dove-ish role didn’t induce a wide emotional response and willingness to talk about it extensively. Meanwhile, some noted that leaders should respect superiors if expecting the same attitude from followers towards them. At the same time, such respect to superiors should be deserved by them, and may take a form of value congruence.\n\nThe leader’s unfair behavior (“fairness”, X6) in sharing resources was unanimously noted as morally bad. Favoritism, as a special case of unfair conduct, was sharply condemned by all interviewees. In contrast, the avoidance of favoritism induced a positive followers’ reaction. All unanimously supported the recognition of productive efforts, regardless of the leader’s personal sympathies. The recognition of somebody’s contribution to the result by a leader was perceived as fair and good, whereas unfair behavior was noted as negatively impacting trust.\n\nThe leader’s respect to prior possession (“property”, X7), was regarded as morally good by all interviewees. The majority couldn’t find a rational justification for this, and stressed emotionally that taking what does not belong to you is absolutely wrong. Some perceived respect to property as a matter of personal respect.\n\nSuch a permanent noting of terms ‘respect’ and ‘trust’ requires attention, as these terms are not an explicit part of basic moral values as they suggested by MAC. The word ‘respect’ was mentioned numerously by every interviewee, or 186 times overall across the entire dataset. Besides the above-noted respect for a person as associated with respect to property (Participant 6), the term is related to respect to the position in hierarchy as recognition of the right to behave in a certain way (Participant 1), respect as admission of personal boundaries of another person (Participant 12), respect to the right of others for having personal opinion (Participant 14). Participant 4 placed respect in a context of reciprocal exchange in a straightforward way:\n\n… this is respect … ; we agreed, and that means we have a contract. You owe me then. And I owe you—to protect you, to defend your rights, etc. But this is a contract, you have to abide by it, you have to do certain things in time with a required quality (Participant 4).\n\nRegardless the context, respect emerges as a derivative of the recognition of the right of somebody else to act in a certain way or to possess something, which in turn comes from the reciprocal attitude that implies behaving with others the way that persons expect others to behave towards them. Therefore, respect has not been considered as an independent construct within the theoretical framework of the present research, as it can be reduced to Curry’s (2016) MAC basic reciprocal behavior.\n\nThe word “trust” in various forms was used in the interviews over 300 times, which highlights its importance for the participants. All interviewees agree that ethical leaders can be trusted, and that trust is essential for a leader. Trust was prevalently noted by the interviewees as a product of compliance with ethics. That is, living one’s personal life in an ethical manner was pointed out as an element of a self-sacrifice, and some interviewees perceived it as an important cue of the leader’s readiness to take a similar attitude towards a group, as such consistency in behavior is treated as a prediction for the same behavior in the future.\n\nIn all cases trust and confidence were mentioned in the context of behavioral predictability, which is perceived as important for all aspects of social life. Such a feature is consistent with recent literature, which considers the value of moral behavior in evolutionary terms as predictable, and thus saving the organism’s metabolic cost of adaptation in future cooperation (Theriault, Young, & Barrett Feldman, 2021). Given the variety of possible moral behaviors that may be expected in future, trust appears rather as a composite phenomenon which can be explained as a combination of basic moral elements within Curry et al.’s (2021) combinatorial hypothesis. This was frequently noted in interviews, such as “something so systemic and big, but consisting of such small [things]” (Participant 5).\n\nAll interviewees point to the employees’ congruence in values with the company’s leader. Such a congruence is mentioned in various contexts or ways 45 times as a prerequisite for the evaluation of a leader as ethical ( Table 26). Meanwhile, the dominant participants’ sentiment is unwillingness to work together with a leader if there is no congruence in values, and expectation of decrease in the leader’s perceived ethicality if the congruence in values disappears.\n\nHence, the directionality of value congruence influence on perceived level of ethical leadership should be considered established. However, there is evidence of the opposite way of influence, though opinions on that way are controversial. Whereas nine participants asserted that their values cannot change as a response to an ethical leader’s behavior, 10 interviews showed that in certain circumstances such an influence is possible ( Table 26). Therefore, the congruence and perceived level of ethical leadership represent rather a positive feedback loop, than just a uni-dimensional influence of value congruence on evaluation of a leader, though the latter was mentioned substantially more frequently.\n\nAlthough the directionality hypothesis was supported, and the overall evaluation of a leader as ethical was noted as composite, “they are made up of little things” (Participant 2), the impact of different basic moral values varied. Some moral values turned out to be unimportant for the evaluation, in case the congruence in others is not felt or disappears, representing an asymmetry in perceived and assessed importance of values for the evaluation of a leader. When explaining why one or another MAC moral behavior is important for an ethical leader, most answers eventually reduced that importance to group interests or reciprocity ( Table 27). Other MAC values are either not mentioned in this context, or are mentioned episodically throughout the entire dataset, and thus neglected.\n\nThe importance of congruence on a certain value in context of other values may represent a mediation relationship. If the value congruence Xn influences “perceived EL” stronger when the mediating congruence XM is present, that may entail substantial implications for practitioners, as it represents an evident reason to concentrate on the mediator in daily practice. This does not refute RH2, which posits the causal influence of congruence in each MAC value on the perceived ethicality of a leader, though such an influence in some cases appears to be indirect. The results of mediation analysis are provided in the next section.\n\n\nDiscussion\n\nAs reported above, the results from Phase 2 showed the interviewees’ unanimous unequivocal support for the influence of congruence in MAC basic moral values on the perception of a leader as ethical, though a positive feedback loop was also present in some extent. This means that the second condition of causal inference—directionality—is fulfilled. The third condition—unconfoundedness—is fulfilled fully for the influence of congruence in “group”, “reciprocity”, “fairness” and “property”, and partially for congruence in “kin”, “heroism”, and “deference”, on the perceived level of ethical leadership, as outlined below.\n\nAlthough both research phases demonstrate interdependence between congruence in some MAC values in their influence on the perceived level of ethical leadership, the results of the qualitative phase demonstrate no signs of conflation of the MAC values by the participants. Despite the statistically significant positive pairwise correlations between the MAC variables for some pairs, Phase 2 demonstrates their distinctness and relevance to the moral domain, which is consistent with recent research on the cross-cultural universality of the MAC values (Alfano et al., 2022; Curry, Mullins, & Whiterhouse, 2019b). Partial correlation analysis demonstrates that any of the MAC variables can interfere with the association between some other MAC variables and the evaluation of a leader as ethical. Therefore, given that the directionality condition has been considered established, mediation analysis was employed to identify whether there are MAC variables causally mediating the influence of other MAC variables.\n\nStatistical simple mediation analysis (MacKinnon et al., 2007; Preacher, Rucker, & Hayes, 2007) of the data gathered in Phase 1 suggests that 16 out of 42 possible combinations of MAC values in Xn→XM→Y relationships may be mediating, where XM stands for the MAC variable that mediated the influence of Xn MAC variable on the perceived level of ethical leadership ( Table 28). The data collected by Phase 2 provides sufficient qualitative evidence supporting only six of these potential mediations. Hence, the triangulation of both studies led to the inference on the mediating role of the congruence in “group” and “reciprocity” MAC values in the influence of congruence in “care for kin”, “heroism” and “deference” on the perceived level of ethical leadership ( Table 29). In the meantime, the influence of congruence in “fairness” and “property” MAC values was considered as direct.\n\nTherefore, the three conditions for causal inference regarding the influence of congruence in MAC values and the perceived level of ethical leadership are fulfilled for “group”, “reciprocity”, “fairness” and “property” MAC values, and their influence is thus considered as direct and causal. The influence of the remaining three MAC values, namely “care for kin”, “heroism”, and “deference” is indirect and causally mediated by “group” and “reciprocity”. This inference resulted in the amended path model depicted by Figure 3.\n\nThe figure depicts the resulting causal influence model, based on the research findings. Dashed lines denote mediated relationships. Each Xn signifies perceived congruence in respective MAC basic moral value (Curry, 2016). Y stands for perceived ethical leadership (Brown et al., 2005). The moderating role of the leader’s behavior visibility to the followers and their cumulative communication duration is also depicted.\n\nFor the population of both research phases, demonstration of fairness and respect to prior possession directly influences the perceived level of ethical leadership. The display of loyalty to the group and reciprocal behavior has the same effect, but they also play an additional role as mediators in influence of congruence in care for kin, heroism and deference on the followers’ moral evaluation of the leader. Being the way in which stimulus leads to response (MacKinnon et al., 2007), mediation in this case implies reasoning behind the hierarchy of importance of the MAC values.\n\nThat is, leader’s care for kin is important because it signals to followers that their leader will similarly take care of the group. Being assertive and sometimes dominant within the group is important because it leads to better group performance. Being forceful outwards is important when it protects group members and aims to enhance the group’s prosperity. The leader’s deference to superiors is important because it brings stability to the group’s future. Without referencing the group’s interests, all these three MAC values lose their importance for ethical leader evaluation.\n\nIn a similar vein, reciprocity impacts the influence of congruence in care for kin, heroism and deference on the leaders’ perceived ethicality. Reciprocity is referred to as respect in the interviews, where it was frequently mentioned in a context implying the leader’s recognition of a deserved right to expect or receive or possess something. This perceived deserved right means the expectation of reciprocal behavior in exchange for actions undertaken in the past. The display of respect here applies not only to behavior towards followers, but also to all other stakeholders. It appears to be a value in itself, regardless of the personal interests of an interviewee. Hence, a dominant or assertive leader’s behavior is valuable only if respect is genuinely displayed, and respectful actions are undertaken. Deference is valued if it is the manifestation of respect to seniors or superiors. Care for kin is important as respect to a family, which serves as a predictive signal of respectful behavior towards followers.\n\nHence, the degree of influence on the evaluation of a leader as ethical exerted by congruence in such MAC values as care for kin, heroism, and deference depends on the genuine subjection of such a behavior to the group’s interests, and the degree of reciprocity in wider terms that is displayed by the leader. Practically speaking, congruence with followers on these two mediating MAC values should be the first priority for a leader aiming to earn evaluation as ethical, along with fairness in distributing the disputed resources and respect to prior possession. In other words, to justify any decision without risking losing followers’ ethical evaluation, the leader must operate with care for the group, reciprocity in actions, and fairness in resource distribution, paying full respect to others’ property.\n\nWhile appeal to heroism, deference, and care for family are not expected to give a substantial effect on the perceived level of ethical leadership, this does not mean that they are not valued by followers or that they have no influence on evaluation at all. In a hypothetical situation when group members were to elect one of two leaders equally perceived as devoted to the group, and congruent with them in feeling the importance of reciprocity, fairness, and respect to prior possession, they will most likely elect that person who is perceived better in family values, heroism and deference.\n\nThe interdependence between MAC values appears to be even more complex than the mediation discussed above. As a matter of common sense, moral assessment should be a composite phenomenon, and the qualitative phase provides empirical support for such an intuitive guess. The data collected in Phase 2 provided clear evidence of the insufficiency of congruence in one standalone basic moral value for moral assessment. In the same vein, the data show limited ability of a follower–leader perceived incongruence in one standalone basic moral value to destroy the perception of the leader as ethical, given the inevitable influence of other values. The interviewees point to moral assessment as a complex phenomenon comprising numerous small factors. In the meantime, besides the value hierarchy and moral assessment complexity in ethical leadership, there are more findings unforeseen in the beginning of the research.\n\nThe data for Phase 2 demonstrate possible counter-productivity of the moral management factor, which represents one of the pillars of Brown et al.’s (2005) concept of ethical leadership. The interviewees argue that excessive talk on ethics, or inconsistency of that talk with a leader’s behavior, results in lowered evaluation of the ethical leader. This finding is consistent with recent research (Pircher Verdorfer & Peus, 2020). Nevertheless, this study supports the main proposition of ethical leadership theory, which posits that the exemplary role of a leader acts as the main factor in the leader’s influence on followers.\n\nWhile the causal positive influence of congruence in MAC values on the perceived level of ethical leadership was found established, some specifics of such influence were not evident before Phase 2 was conducted. The qualitative data demonstrate the special role of a leader, who apparently is perceived differently compared to other people in the group. The way the interviewees explained what is right and wrong in the behavior of a leader leaves the impression that in their view, there is the leader and “the others,” two parts of a team with equal weight, no matter how large the “others” part is.\n\nRecent literature suggests that assessing the morality of a leader differs from assessing others (Crockett, Everett, Gill, & Siegel, 2021). For example, instrumental harm attributed to a leader can be viewed as morally good, as it entails benefit for the group, while it is morally unacceptable when caused by peers. Crockett and colleagues suggest that the deontological approach to the moral assessment of peers offers more certainty in terms of future inter-personal comfort in possible cooperation, whereas the peers’ tendency to apply instrumental harm entails future threat to an individual and may thus be condemned, even if it brings the utility for the group.\n\nIn contrast, people apply the utilitarian approach more willingly when evaluating leaders (Crockett et al., 2021). Due to the dependence of their actual or envisioned safety and well-being on leaders’ actions, people tend to afford instrumental harm to certain group members if it results in their group’s benefit, and thus to assess such behavior as morally good. Such an explanation gives the basis to understanding the value hierarchy revealed by this study.\n\n\nLimitations of research\n\nAlthough the sample size of the Phase 1 survey is satisfactory according to criteria suggested by the literature for regression analysis (see Fritz & MacKinnon, 2007), this might not be sufficient for good model fit in different circumstances. Keeping in mind Schreiber et al.’s (2006) arguments, it is recommended for future research to retest model fit on samples exceeding the product of 10 and the number of measured parameters. Moreover, to be generalizable across multiple groups, all the findings on association, moderation and mediation ideally need a retest in a multi-site research design with a substantially larger sample of at least M × N × 33 respondents, meaning M groups multiplied by N categories and 33 valid answers in each category.\n\nThe content validity of the MAC items of the resulting modified instrument might represent an issue for future research and practical applications. These items were adopted from Curry, Chesters, and Van Lissa (2019a), who, in turn, drew them from the peer-reviewed literature. However, Curry et al. argue that these items may measure different aspects of morality, even though they are within a designated group of typical solutions for cooperation problems. For better model fit, the original MAC-Q set of items have been reduced from an overall six per each MAC value, combining Judgment and Relevance scales, to just two items per construct, which can narrow substantially the possible aspects of morality covered by the resulting scales. Further research should examine their exhaustiveness and, thereby, the content validity of the entire instrument.\n\nDue to the focus on a company involved in the Russian logistics sector, the findings of both research phases are limited in generalizability to wider cultural and industrial contexts. Tested in different organizational circumstances, the hierarchy of congruence in MAC values might vary. Similarly, as the Russophones are spread across different countries that may culturally influence local diasporas (Zabrodskaja & Ivanova, 2021), the hypotheses of this study would not necessarily be borne out by data from other countries’ Russophones. In the meantime, the qualitative data received affords the expectation of transferability to other groups, as the most participants’ explanations were made in contexts wider than the Company or industry or country. Nevertheless, the results of the present research may be limited in application to a possible wider cultural range of Russophone communities across the globe, and the hypotheses should be re-tested on samples collected in other countries’ diasporas to be applicable to Russophones worldwide.\n\nAlthough these limitations may prevent the theoretically sound generalization of the results to populations other than the focal one for the present research, this does not mean that these results will necessarily be false for other groups. While further research might examine wider generalization for the sake of scientific rigor, it appears already valuable to employ the findings of this thesis in applied research, management consultancy, and leadership practice.\n\n\nTheoretical and practical implications\n\nBanks et al. (2021) point to the lack of research on factors influencing the association between ethical leaders’ behaviors and their perception by followers. Similarly, Brown and Mitchell (2010) point to the lack of research on the influence of followers’ moral identity on the perception of a leader as ethical or unethical. This study contributes to closing this gap by providing empirical support for the influence of followers’ perceived moral value congruence with a leader on the perceived level of ethical leadership. In addition, it contributes to literature on the MAC and ethical leadership by empirical examination of the causal association between the concepts of both theories. Besides that, the discussion of MAC values in terms of perceived value congruence also turns out to be novel to this theory.\n\nTesting of MAC-Q items in a Russian-speaking environment and validating their modified composition widens their cross-linguistic and cross-cultural application to Russophone context. The same is true with the ELS instrument, which had not been applied to Russophones in literature available to the authors. Thus, this study contributes to the MAC and ethical leadership research domains by testing these theories and corresponding instruments in the Russophone context.\n\nThe theoretical method employed in this thesis, namely quantitative inquiry with hierarchical regression analysis followed by semi-structured interviews, can be employed by leadership theorists, organizational consultants, or management practitioners for the assessment of the interdependence in the influence of MAC basic moral values on perceived level of ethical leadership within a given organizational context.\n\nDue to established positive group outcomes of the high perceived ethical leadership (Bedi et al., 2016), the enhancement of this perception has an evident practical rationale. Hence, the degree of importance of each MAC element represents valuable information for practitioners aiming to improve the perceived level of ethical leadership. Armed with such knowledge, leaders can adjust their behaviors accordingly, subsequently enhancing followers’ ethical evaluation, which results in enhancement of group’s outcomes.\n\nMoreover, given that congruence in “care for kin”, “heroism” and “deference” moral values is contingent on follower–leader congruence in such MAC elements as “group” and “reciprocity”, the leader’s behavior and narratives reflecting these values should be placed into the context of the safety of and utility for the group, and of respect for others’ efforts and achievements, if the leader aims to attain a better result. If applying the suggested method in different organizational contexts will reveal other value hierarchies, leaders can adjust their behavior accordingly in order to achieve better perceived value congruence.\n\nOn the other hand, the above-noted positive feedback loop of the influence of ethical leadership on moral value congruence suggests that followers’ moral values could change in certain conditions. From the practical standpoint, moral value management in a group may appear suitable for pursuing ethical leaders’ purposes. Knowledge of congruence in particular MAC elements may serve as a guide for leaders’ choices regarding moral manifestations to change their followers’ MAC values preferences, which can eventually enhance organizational outcomes in accordance with the ethical leadership theory.\n\n\nFurther research\n\nFuture research is necessary to expand the theoretical and practical implications of this study. Besides testing its findings beyond the limitations outlined above, some avenues for academic inquiry represent interest in the advancement of knowledge on moral psychology and ethical leadership. This section suggests such avenues from the authors’ perspective, though these suggestions under no circumstances should be considered an exhaustive set of potentially interesting research areas, as the field’s potential scope appears to be substantially wider.\n\nThe core of leadership phenomena is a leader’s influence on followers (Northouse, 2019). Brown et al. (2005) build the ethical leadership theory on social learning theory, which involves the role model concept. Gibson’s (2004) concept of a behavior induced by role models may be decomposed to four components, namely attributes of people in social roles, perception of personal attributes as similar, the desire to increase such similarity, and the emulation of that similar behavior. While the perception of similarity was approached by this study to some extent, the phenomenon of social role attribution of MAC elements has not been touched. The knowledge of mechanics underlying the association between MAC values attribution, perceived congruence, and the desire to act similarly turns out to be essential for the understanding of ethical leaders’ influence, so it needs to be addressed in future studies.\n\nResearch on the dynamics of the influence of the particular composition of MAC values demonstrated by a leader could make a substantial theoretical contribution given the interdependence of values in moral assessment demonstrated by this research. Such an interplay of MAC values may represent multiple mediation relationships, or depend on the degree of the follower–leader communication frequency, or demonstrate some other specifics that cannot be foreseen based on the findings of this research. More research is thus required for a deeper understanding of the relationship between MAC basic moral values and ethical leadership.\n\nThe dynamics of leader’s influence may also depend on the stability of moral evaluation. Recent research shows that moral judgments vary within a week in sacrificial dilemmas (Rehren & Sinnott-Armstrong, 2022). Further research should find an answer to the question of the stability of followers’ MAC value composition. From the practical standpoint, this would provide leaders with knowledge of the moments when the moral accents in their behavior should be re-adjusted to followers’ moral expectations.\n\nNewly formed teams may differ in moral consensus achievement dynamics compared to established groups. Knowledge of the dynamics of belief equilibrium formation can be beneficial for the practice of ethical leadership in early-stage start-up management or in mature corporations’ efforts to expand to new markets. Gavrilets (2021) suggests an approach to modeling group behavior as a function of norms, personal beliefs, and material payoffs. The application of this or a similar approach to group dynamics might entail valuable theoretical and practical implications in the ethical leadership domain. Similarly to newly-established groups with possibly varying moral prioritization across members, mixed-culture teams may face the same specifics and thus represent a promising area for future research.\n\nThe differences in moral assessment imposed by either cultural or any other conditions may be reduced to variance in MAC values prioritization, according to the combinatorial hypothesis proposed by Curry et al. (2021). Due to its potentially substantial theoretical and practical implications, it deserves extensive cross-cultural qualitative tests. The qualitative data of Phase 2 provides supporting evidence for such moral values as trust and respect. As the hypothesis claims that any moral value may be reduced to the combination of MAC basic moral elements, qualitative inquiry into wide spectrum of moral values is required.\n\nBesides the prospective research areas mentioned above, there may be others—for example, the influence of the MAC values on narratives that reflect moral evaluation (Kim & Crockett, 2022), the way normative evaluation shapes the behavioral patterns (Theriault et al., 2021) in the context of the MAC and ethical leadership, and so forth. Answers to such questions have practical importance for a group’s behavior engineering, meaning by this the leaders’ fine-tuning of their own narratives and behaviors to achieve the desired followers’ behavior. Such social engineering appears to be a wide and interesting topic for ethical leadership practice.\n\n\nConclusion\n\nKeeping in mind the limitations discussed earlier, the data gathered in both phases of this study supports the following statements at least for the population studied.\n\nFirst, there is a positive association between perceived congruence in MAC basic moral values and the perceived level of ethical leadership, and, in this association, perceived value congruence causally influences the perceived ethicality of a leader, though there is a positive feedback loop to a certain extent. Second, this influence is moderated by the proximity of the leader, understood as the extent to which followers can observe the leader’s behavior, combined with the frequency and duration of the leader’s communication with the followers. Third, the leader’s values observed by the followers are not equal in their influence on the perceived level of ethical leadership; so that influence of congruence in “care for kin”, “hawkish” and “dove-ish” basic moral behaviors on perceived ethical leadership is mediated by congruence in two other basic moral behaviors, namely “loyalty to the group” and “reciprocal exchange”, while congruence in “fairness” and “respect to prior possession” positively influences perceived ethical leadership without mediators.\n\nBesides this, the results of practical application of the morality-as-cooperation and ethical leadership theories in a Russophone organization supports their validity in Russophone contexts. Over and above this theoretical contribution, instruments and method have been offered to ethical leadership practitioners for the assessment of perceived congruence in MAC values, perceived level of ethical leadership, and their interdependence in the Russian language context.\n\nThis study was conducted in accordance with the ethical standards of SBS Swiss Business School and adhered to the ethical principles outlined in the Declaration of Helsinki. Approval for conducting both phases of the research was obtained from the SBS Swiss Business School Ethical Committee. The informed consent was received from each participant in both study phases by checking the corresponding box in the Web-form in the Phase 1, and in written and oral forms in the Phase 2.\n\n\nAuthor contributions\n\nAlexey Belinskiy: Conceptualization, data curation, formal analysis, funding, investigation, methodology, project administration, resources, visualization, writing — original draft preparation.\n\nCarl Olsen: Supervision, methodology, validation, writing — review and editing.\n\nhttps://doi.org/10.17605/OSF.IO/SZ93M",
"appendix": "Data availability\n\nOpen science framework: Influence of MAC Moral Value Congruence on Perceived Level of Ethical Leadership. https://doi.org/10.17605/OSF.IO/42TNC\n\nThis project contains following data:\n\n1. Anonymized quantitative results are provided in a.dbf file containing raw Likert values.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nRestricted data: Interview transcripts are available upon request. While anonymized, these transcripts may contain sensitive information about the sample company. As per agreement between the authors and the sample company, qualitative data can only be shared with third parties who demonstrably have no intention or ability to harm the sample company’s business. This determination is at the Corresponding author’s discretion and requires the requesting party to sign a Confidentiality Agreement. The agreement form (Confidentiality agreement for the qualitative data disclosure.pdf ) can be downloaded from https://doi.org/10.17605/OSF.IO/42TNC.\n\nOpen science framework: Influence of MAC Moral Value Congruence on Perceived Level of Ethical Leadership [Dataset]. OSF. https://doi.org/10.17605/OSF.IO/42TNC\n\nThis project contains following data:\n\nThe original, the original interview script and its English translation, and the interview written consent form.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThe reporting style adheres to the APA JARS guidelines, namely JARS-Quant (Appelbaum et al., 2018) for the quantitative Phase 1, and JARS-Qual (Levitt et al., 2018) for the qualitative Phase 2.\n\nReferencing style: The Academy of Management Journal http://aom.org/uploadedFiles/Publications/AMJ/AMJ Style Guide(1).pdf style guide (with only italic book and journal titles).\n\n\nReferences\n\nAlfano M: Varieties of moral motivation: Empirical perspectives.Copp D, Rosati C, editors. Oxford Handbook of Ethical Theory. Oxford University Press; 2022.\n\nAlfano M, Cheong M, Curry O: Moral universals: A machine-reading analysis of 256 societies.2022. 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Publisher Full Text\n\nGravetter FJ, Wallnau LB, Forzano L-AB, et al.: Essentials of statistics for the behavioral sciences. Cengage Learning; 2020.\n\nGuest G, Bunce A, Johnson L: How many interviews are enough? An experiment with data saturation and variability. Field Methods. 2006; 18(1): 59–82.\n\nHaidt J: The righteous mind: Why good people are divided by politics and religion. Pantheon/Random House; 2012; xvii, 421.\n\nHaidt J, Joseph C: Intuitive ethics: How innately prepared intuitions generate culturally variable virtues. Daedalus. 2004; 133(4): 55–66. Publisher Full Text\n\nHair JF, Ortinau DJ, Harrison DE: Essentials of marketing research. Vol. 2. .Irwin New York, NY: McGraw-Hill; 2010.\n\nHayes SC, Pankey J, Gregg J: Acceptance and commitment therapy. Anxiety Disorders: A Practitioner’s Guide to Comparative Treatments. 2002; pp. 110–136.\n\nHennink MM, Kaiser BN, Marconi VC: Code saturation versus meaning saturation: How many interviews are enough? Qual. 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}
|
[
{
"id": "350483",
"date": "23 Jan 2025",
"name": "Thomas Li-Ping Tang",
"expertise": [
"Reviewer Expertise Work Motivation",
"Monetary Wisdom",
"the Love of Money Attitudes",
"Monetary Aspirations",
"Business Ethics",
"Behavioral Economics",
"Cross-cultural studies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: Influence of perceived congruence in basic moral values on perceived level of ethical leadership: A Russophone organization case\nI offer my review comments below.\nThe authors of this paper provide an interesting review of the literature, present several hypotheses, collect data from 56 participants of a Russian logistics company in Moscow’s HQ, and present some interesting expected and unexpected results. The authors have engaged a great deal of work into the design, conduct, analysis, and write-up of this paper. I have enjoyed reading this paper.\nMy goal of this review is to help authors improve their presentation of ideas and enhance value-added theoretical, empirical, and practical contributions to the journal, F1000Research, specifically, and the field of management and business ethics, in general. I offer the following comments with the hope of helping authors maximize their value-added contributions and future citations.\n1. First, authors must demonstrate the extent to which their article makes specific, significant, and value-added theoretical, empirical, and practical contributions to the literature: theoretical (41%), empirical (42%), and practical (17%) (Rynes, 2005). Interestingly, theoretical and empirical contributions are equally important. Bartunek J, et al., 2005 (Ref 1)\n2. For the Title of your article, we must create a good first impression to attract readers’ attention and their future citations. Please incorporate the following ideas into your Title.\n\nFollowing Search Engine Optimization (SEO), Springer’s instructions for authors recommend that your title’s first 55 characters with space be brief and contain words that are useful for indexing. Authors must write succinctly, focus on what is important, and delete unnecessary words. Think: “What’s Important Now (WIN)? Holtz, L. (2006). Wins, losses, and lessons: An autobiography. HarperCollins.\nAccording to Leonardo da Vinci: Simplicity is the ultimate sophistication.\n3. Does your main Title capture the most significant aspect of your study? Please ask an interesting question as the main title and provide the answers in the subtitle. Please demonstrate: Why is this important? Why do we want to know?\n4. To simplify, please consider the following suggestion: Perceived moral values congruence impacts ethical leadership: Evidence from Russia\n5. Abstract, Methods. I would expect to see more details regarding your study, e.g., the contextualization (location of your data collection), the population, your sample, and sample size. I assume that you are very proud of this study because you have collected your data in Russia, a very unique and special sample. Thus, you must highlight these bright spots in your Title, Abstract, and Keywords. See my point #2.\n6. Readers and the AI’s search engine optimization (SEO) will identify your published article more quickly and present it at the very top of the search results, if you repeat these critical constructs in your Title, Abstract, and Keywords.\n7. Results: Please change/edit your statement to: (r (54) = [.34; .64], p < .05). Please make corrections throughout the article. The letters “r” and “p” have special meaning in statistics.\n8. In the following article, the authors identify 28,774 articles and explore the writing styles and citation count. Boghrati R, et al., 2023 (Ref 2) To increase your communications’ impact, please use first person, present tense, active voice, and emotional language to increase readers’ arousal, feelings, and memory, and enhance future citations. Please re-write your whole article following the instructions below:\n\nFunctional words explain 4% of the overall variance explained and 11% of language’s impact on citations. Use Present tense: It helps make the content current, in the moment (literature review), revealing its importance and impact. Use First-person pronouns, like “I” or “we”: It helps authors take personal ownership of arguments, hypotheses, findings, and contributions, impress readers as knowledgeable, important, and impactful, and have authority, power, and success. Use Indefinite articles (i.e., “a” or “an”): It makes content much broader and generally applicable than definite articles (i.e., “the”).\n\nUse First-person (“I” or “we”), fewer articles, or prepositions. Simpler front ends will lead to high citations. Use Active Voice: For example, we conducted this research. We collected the data. Avoid Passive Voice: For example, research was conducted. Data were collected. Use Emotional Language: Don’t just cite numbers and statistics. Do provide real examples and demonstrate the consequences of critical events. Corruption caused the destruction of Enron and Arthur Andersen, the incarceration of executives, and the disruption of 110,000 employees' careers worldwide. (Tang et al., 2023, p. 927).\n9. Incorporate contextualization into theoretical and practical implications. Can you find these patterns only in Russia or other cultures (nations)? Why? Why not? Johns G, 2017 (Ref 3) Rousseau D, et al., 2001 (Ref 4) Tsui A, 2009 (Ref 5) Whetten D, 2009 (Ref 6)\n10. Introduction. I expect to read the three-page Introduction with the following expectations. An exemplary Introduction serves three significant purposes and attempts explicitly to (1) show the significance of the topic, “hook” readers’ interest, attract their attention, and motivate them to read further, (2) identify the theoretical gaps, inconsistencies, controversies, and deficiencies of this topic in the literature, and (3) provide a brief preview of your specific value-added theoretical, empirical, and practical contributions to the literature that will fill the gaps and resolve these issues. The award-winning authors had written the same Introduction, on average, ten (10) times, before they published their articles. Grant A, et al., 2011 (Ref 7) Hemingway took writing very seriously. Hence his quote: “Don’t get discouraged because there’s a lot of mechanical work to writing…I rewrote the first part of A Farwell to Arms at least fifty (50) times”.\n11. In your Introduction, you state: “Curry (2016) proposed the morality-as-cooperation (MAC) theory”. I use this term, search the Scopus database, and find 30 articles: 10 in 2024, 5 in 2023, 4 in 2022, 7 in 2021, 3 in 2020, and 2 in 2019. I take a quick look. You have not cited any of these 10 articles published in 2024 on your Reference list. It appears that your literature review is dated. Please keep it current and up to date.\n12. Develop a robust theory in the Introduction. Show your theoretical model, list all the constructs, and explain the relationships among these components. You mention nothing regarding Relevance and Judgment in your theory until the Measurement section and Table 2. Don’t “surprise” your readers.\n13. Please read Curry, Mullins, and Whitehouse’s (2019) interesting cross-cultural study, digest the contents carefully, identify the gaps, and quote key ideas to set it up for your current research.\n14. To help you revise this paper and identify the gap of the literature, I offer my suggestions below: In Curry et al.’s (2019) article, we discover several important clues that demonstrate the robust theoretical and empirical gaps in the literature. We list them briefly below. In their reply to several eminent authors’ comments at the end of their article, the authors mention that “Bloom questions whether MAC is a ‘psychological theory’” (Curry et al., 2019, p. 63). “Hence moral value will exhibit a multifactorial structure, varying on these seven dimensions” (p. 63). “Further research will be needed to test the subsequent prediction that individual (and cultural) differences in moral values will reflect the value of cooperation at different stages of development (Curry 2005:182; Sheskin et al. 2014), and under different social conditions” (Curry et al., 2019: 63-64). “Moreover, the authors observe that they ‘were not able to measure within- or between-society variations” (p. 63).\nFollowing Curry et al.’s (2019) excellent points above, the present study answers their calls, expands “the theory of Morality-as-Cooperation” (MAC) developed, qualitatively, in the field of anthropology to a new context, and treats Morality-as-Cooperation as a “psychological theory” (p. 63). We apply MAC’s multifactorial structure and explore this construct’s impact on individuals’ ethical behaviors, a brand-new perspective in a new academic field to establish it validity.\nEmpirically, we collect data from Russia, a highly under-researched region of the world. To the best of our knowledge, no researchers have investigated the MAC construct among citizens in Russia. We apply recent advanced and powerful measurement theory (formative vs. reflective models), structural equation modeling (SEM) technique (IBM SPSS Amos), and investigate individuals’ potential within- and between-subjects differences. A formative SEM model allows us to treat MAC’s seven dimensions as independent and yoked antecedents of the unmeasured latent construct, MAC, which leads to the outcome variables. We test the theoretical SEM model across genders, age groups, and organizational levels using Mult-Group Confirmatory Factor Analysis (MGCF). These methods allow researchers to identify the relative contributions of MAC’s seven subconstructs to the latent construct, MAC, and the consequences, and examine within- and between-subjects differences across various contexts. Scholars can simultaneously inspect the correlations among these seven subconstructs. Specifically, MAC’s seven independent dimensions may make positive or negative, and significant or non-significant, contributions to the latent construct and the outcomes. Our study’s novel findings offer robust theoretical, empirical, and practical implications to the management and business ethics literature.\n[Here I am showing you that ideally this is what you can do. You must have a large sample size (N = 456) and additional outcome variables to accomplish these objectives. If you have data from more than 30 countries, then follow the 30*30 rule to conduct cross-level analysis. See more discussion on these issues below]\n15. According to Curt Lewin: “There is nothing more practical than a good theory”. Please also see Tang (2024b) below: Tang, T. L. P. (2024b). Monetary Wisdom: Crafting an inspirational, memorable, and practical theory. In Tang, T. L. P. (Ed.) (2024). Monetary wisdom: Monetary aspirations impact decision-making. Cambridge, MA: Academic Press, An Imprint of Elsevier. Paperback ISBN: 9780443154539; eBook ISBN: 9780443154546\n\nA theory is an explanation. It takes a blizzard of facts and observations and explains your key ideas in the most basic terms. A theory is incomplete and oversimplified. However, it helps readers understand. An excellent paper has a strong theory.\n16. A good paper with a strong theory should have well-constructed logical arguments, rich and novel insight, adequate conceptual development, and a deep appreciation for the relevant literature. Please read the following articles for more information. Alvesson M, et al., 2011 (Ref 8)\nTang, T. L. P. (2021). Creating inspirational, memorable, and practical theories: The lessons of The Last Supper. In G. R. Ferris, P. L. Perrewé, & A. Akande (Eds.). Emerging trends in global organizational science phenomena: Critical roles of politics, leadership, stress, and context (Chapter 9, 183-195). Hauppauge, NY: Nova Science Publishers.\nHere are some guidelines for reviewing papers submitted to top journals (or the Academy of Management annual conference). Please ask yourself and examine your composition from the Reviewer’s perspective:\n\n Introduction\nIs there a clear research question with a solid motivation behind it? Is the research question interesting? After reading the introduction, did you find yourself motivated to read further? Theory Does the submission contain a well-developed and articulated theoretical framework? Are the core concepts of the submission clearly defined? Is the logic behind the hypotheses persuasive? Is extant literature appropriately reflected in the submission, or are critical references missing? Do the hypotheses or propositions logically flow from the theory?\n17. Besides, please follow Steve Jobs’ mantra: “Focus and Simplify.”\nSee also Adam Grant’s 2016 book on Originals.\nThe 1986 Nobel Laureate in Economic Sciences, Prof. James M. Buchanan, stated: “Economics requires expository writing skills, logical structures of analysis, and a grounding in ultimate reality.”\nOn November 21, 1991, James M. Buchanan revealed the secret to his success:\n“Hard work, a sense of self-confidence, a willingness to challenge all authority, scientific or otherwise”.\nAlbert Szent-Gyorgi (born in Budapest, Hungary, the 1937 Nobel Laureate in Physiology or Medicine, discovered Vitamin C and its components) stated:\n“Discovery consists of seeing what everyone has seen, and thinking what no one has thought”.\nDid you cite an interesting story to attract readers’ attention? Is your research relevant to real people in ultimate reality? This is sadly missing.\n18. Specifically, your Introduction leads readers to a theoretical model. Please explain the components of your model and the relationships among these components. Please spell out all these constructs clearly and explicitly. Provide an overarching theoretical model. Define all key constructs at the beginning of your Theory and Hypothesis.\n19. Provide detailed theoretical arguments (research findings) regarding how and why the relationship between X and Y is moderated and mediated by other variables (M and Z). Explain all the theoretical arguments regarding arrows in your model, not just the boxes. Thomas D, et al., 2011 (Ref 9)\n20 As Sutton and Staw stated: “But it still contained no discussion of what these theories were about and no discussion of the logical arguments why these theories led to the author’s predictions” (1995: 373). “Data describe which empirical patterns were observed and theory explains why empirical patterns were observed or are expected to be observed” (p. 374). Sutton R, et al., 1995 (Ref 10)\n21. A complete theory must have the following elements: What, How, Why, Who, Where, and When. An interesting paper has the following two critical ingredients: (1) “aha” (what is new here?) and (2) “so-what” (what can researchers and practitioners do with these new findings?). These components were missing.\n22. What makes a theory interesting, notable, influential, and famous? When researchers see a good theory, they find that the theory is not only true but also more importantly, it is challenging the assumptions underlying existing theories in some significant way (Alvesson & Sandberg, AMJ, 2011). The critical element is to ask the “right,” totally original, and creative research questions. Did you challenge any assumptions? Did you offer any counter-intuitive discoveries? If your findings support hypotheses as expected, then, why do we need another study to find out?\n23. Please also make sure that you frame your research question properly (Colquitt & George, 2011) and include all these aforementioned elements in your paper. Colquitt J, et al., 2011 (Ref 11)\n24. Further, it is vitally important that you step back, think deeply, and articulate clearly and explicitly: What was your value-added contribution to the literature? Did you articulate forcefully what we learned in this new paper that we did not know before? The theory is how we move to further research and improved practice. If a manuscript contains no theory, people may question its value.\n25. Please read the following article and understand where you stand regarding your contributions in theoretical terms (theory building and theory testing): Did you develop a new theory? What theories are you trying to test in this paper? With a good understanding of these principles, then, you will be able to craft a better article than the present version in the future. Present an interesting story, attract readers’ interests, and get readers hooked, wanting to know more about your study. Highlight the theoretical glue that connects all the constructs and paths, telling an exciting story. Enhance critical components that make an article exciting, innovative, novel, and counter-intuitively interesting.\n26. The authors explore the ethical issues from the evolutionary moral psychology perspective. This reminds me of Richard Dawkins’ 1976 book, The Selfish Gene, a very interesting and influential idea in scientific and popular thought. You may want to dive deeper into this issue in your theory, hypotheses, and measurement of constraints.\n\n27. You state: “More specifically, few studies focus on follower-leader moral value congruence.” I offer the following comments regarding the use of this term.\n28. We find a lot more than “few studies”. Following Leader-Member Exchange, LMX, the traditional and logical flow of influence is from “the leader” to “the followers”. Scholars have considered person-supervisor fit, the trickle-down effect, and leader-follower value congruence. Please see also Tang et al. (2018b, 2023), discussed below.\nSince managers are nested in a country, CPI at the country level, a Level 2 variable, “exerts a greater downward influence on” individual dishonesty than vice versa (Andersson et al., 2014: 1068). (Tang et al. 2023, p. 931-932) Andersson U, et al., 2014 (Ref 12)\n29. I listed 6 studies related to the trickle-down effect and 20 papers on value congruence as examples.\n\n30. Following your Table 2, you have three items for each of the seven Constructs, X1 to X7, (3*7 = 21), and 10 items for Perceived ethical leadership (21 + 10 = 31). In sum, you have 31 items in your study. Please note that you need more constructs for your dependent variables in your formative SEM model.\nWhen you consider the number of participants in your study, you need to have a ratio of at least 10 participants for each item on your survey questionnaire (N = 310). For a better ratio of 15, you need 465 participants.\n\n31. After reading your Population and Sampling section, I am very disappointed regarding your sample size (N = 56) which is significantly lower than the expected value (N = 310; or N = 465).\n32. Tell our readers about this particular study’s context and the backgrounds of these participants in Russia. Whetten (2009) discussed contributions of theory and contributions to theory together with theories in context and theories of context. Please read the whole special issue of Management and Organization Review.\n33. Since you use the original scales published in the English literature and translate them into the Russian language, did you check the measurement invariance or equivalence of these constructs in a new country, Russia? Please see Tang et al. (2006) for an exemplary demonstration of conducting measurement invariance/equivalence.\n34. Did you check the Common Method Variance (CMV) issue in a study using a cross-sectional design?\n\nMacKenzie, S. B., Podsakoff, P. M., & Podsakoff, N. P. (2011). Construct measurement and validation procedures in MIS and behavioral research: Integrating new and existing techniques. MIS Quarterly, 35 (2), 293-334.\n\nPodsakoff, P. M., MacKenzie, S. B., Lee, J. Y., & Podsakoff, N. P. (2003). Common method biases in behavioral research: A critical review of the literature and recommended remedies. Journal of Applied Psychology, 88, 879-903.\n35. To summarize, please update your literature review, select top research publications in prestigious journals with high-impact factors as your role models, and study, learn, understand, and cite the most recent developments in your research. Identify the gaps, deficiencies, and inconsistencies, develop a strong theory, and explore your niche by selecting proper theoretical constructs and measurement instruments with the highest reliability and validity so that you can resolve the above issues. The design of your empirical study and the development of your theory are the most essential parts of your research.\n36. Please delete all the unnecessary Tables (e.g., null hypotheses, Tables 9 and 22, raw data, pairwise Pearson, measures across genders, age groups, and organizational levels) at the “individual item level”. These Tables make no theoretical or empirical contribution.\n37. You should articulate what the readers have learned that they did not know before. The theory is how we move to further research and improved practice. Please also show the “aha” (what is new?) and “so-what” (what can you do with this new finding?) in your paper. A good article should have these attributes. Please make it explicit and flush your ideas out right in Introduction and Discussion: What, How, Why, and Who, Where, and When. Do you challenge any assumptions? Do you offer any counter-intuitive discoveries? Following your literature review, your hypotheses and findings are obvious. Why do we need another study?\n\n38. Finally, carefully craft each word to enhance cognitive ease and associative coherence so that your paper will be simple, memorable, insightful, rhymed, and easy to read, according to Dr. Daniel Kahneman, the 2002 Nobel Prize Winner in Economic Sciences.\nI hope that you can respond to my concerns above and revise your paper accordingly in your future research. Thank you very much for allowing me to review your work. Good luck with your research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1472
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https://f1000research.com/articles/13-721/v1
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01 Jul 24
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{
"type": "Review",
"title": "Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action",
"authors": [
"Megha M Anchan",
"Guruprasad Kalthur",
"Ratul Datta",
"Kabita Majumdar",
"Karthikeyan P",
"Rahul Dutta",
"Megha M Anchan",
"Guruprasad Kalthur",
"Ratul Datta",
"Kabita Majumdar",
"Karthikeyan P"
],
"abstract": "Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features adhesions caused by estrogen-dependent periodic bleeding. It is characterised by a widely spread fibrotic interstitium that comprising of fibroblasts, myofibroblasts, collagen fibres, extracellular proteins, inflammatory cells, and active angiogenesis found outside the uterus. Thus, fibrosis is recognized as a critical component because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or non-cyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root cause, etiology, and complex pathogenesis of this debilitating condition, makes it challenging to diagnose early and to implement therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Research on understanding the pathogenesis of endometriosis is still ongoing to find biomarkers and develop non-hormonal therapeutic approaches. Current clinical research indicates a close relationship between endometriosis and fibrosis, which is thought to be tightly linked to pain, a major factor for the decline in the patient’s quality of life but little is known about the underlying pathophysiological cellular and molecular signaling pathways that lead to endometriosis-related fibrosis. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease to assess treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article’s goal is to examine recent developments in the field and pinpoint knowledge gaps that exist with a focus on the development of novel fibrotic mouse models for the early diagnosis and treatment of endometriosis and how this knowledge aids in the development of novel anti-fibrotic treatments which opens fresh avenues for a thorough investigation and extended research in the field of endometriosis.",
"keywords": [
"Endometriosis",
"pelvic pain",
"etiology",
"animal model",
"Epithelial-mesenchymal transition",
"fibrosis"
],
"content": "Introduction\n\nEndometriosis is an inflammatory disorder dependent on estrogen and results from the implantation of viable endometrial, epithelial, and stromal cells (a lesion) outside of the uterus, often associated with infertility.1 The condition affects at least 10% (~247 million) of women worldwide, with Asian women reporting the highest prevalence with over ~ 42 million girls and women from India2,3 which can hurt the outcome of IVF treatments.4,5 Endometriosis can result in severe dysmenorrhea, dyspareunia, menorrhagia, excruciating pelvic/abdominal pain, and eventually lead to infertility due to considerable damage to the structure and function of reproductive organs, even compromising entire bodily systems due to the accumulation of fibrotic tissue.6 Even after several decades of research, the etiology is still unclear and dependent on a few key assumptions. The retrograde menstruation theory, embryonic remnants, coelomic metaplasia, immune dysfunction, inflammation and oxidative stress, hormones, dysfunctional apoptosis, microbiome, metabolomics, endocrinology, and genetic expression differences are the main theories of pathophysiology2,7 Currently, the most widely recognized theory explaining how endometriosis begins is “Sampson’s theory”, which holds that the misplaced viable endometrium-like tissue is transferred onto the pelvic peritoneum by retrograde menstruation via the fallopian tubes.8 The diagnosis can take 4 to 11 years due to difficulties in classifying and identifying the disease as well as its peculiar symptoms, as well as a lack of diagnostic indicators.9 The disease’s variable severity can be due to superficial peritoneal, deep peritoneal (DIE), ovarian endometriomas, extra-abdominal endometriosis, and iatrogenic endometriosis.10 According to Maddern et al., endometriosis has a significant impact on a person’s quality of life, their reproductive health, and society at large. Therefore, a thorough understanding of the mechanisms underlying the origin and evolution of endometriosis is crucial for managing and evaluating the risks associated with the condition.11 Although imaging procedures such as transvaginal ultrasonography (TVUS), and magnetic resonance (MRI) imaging are common diagnostic tools, the gold standard diagnosis method for endometriosis remains the histological investigation of lesions obtained after laparoscopic surgery.12 Endometriosis pelvic adhesions have also had a major impact on the American Society of Reproductive Medicine (rASRM) categorization score approach.13,14 It does not, however, account for the pathology-based staging that is based on the normal course of endometriosis and fibrosis aspect which includes epithelial to mesenchymal transition (EMT) or mesenchymal to epithelial transition (FMT), Smooth muscle metaplasia (SMM). This means that patients with fibrotic characteristics and adhesions may fail to get a reliable diagnosis.15\n\nRetrograde menstruation is prevalent in healthy women and only a small population of women develop the condition contributing to the understanding of complex mechanisms that underlie the onset of this challenging condition.16 While 90% of women of reproductive age undergo retrograde menstruation to the pelvic cavity, only 10% of them go on to develop endometriosis. This suggests that the onset and progression of the disease in the peritoneal cavity depend on additional relevant factors.17 This entails understanding how cells from the normal lining of the uterus find atypical locations, multiply excessively, escape immune and apoptotic processes, and acquire the necessary blood supply and nutrients that ultimately result in the formation of aberrant lesions.18 None of the available theories fully captures the intricacies of fibrotic endometriosis, emphasizing the need for additional studies to identify the pathophysiology of endometriosis.19 Therefore, it is imperative to investigate and characterize the molecules involved in the emergence of this crippling disease, including the acquisition of characteristics in these normal endometriotic cells such as increased proliferation, invasion, vascularization, angiogenesis, and migration.20 The formation, invasion, and angiogenesis of fibrotic ectopic lesions have been associated with disrupted immunoregulatory processes and a variety of inflammatory markers, including immune cells, cytokines, chemokines, matrix metalloproteinases, and other substances associated with the immune system.21,22 Thus, a thorough understanding of the mechanisms underlying the origin and evolution of endometriosis is crucial for managing and evaluating the risks associated with the condition. In this review, we describe and comment on existing endometriosis models, research gaps, proposals, or ideas for the most essential and underappreciated aspect of the condition of EMT and fibrosis, and how focused research on it can lead to novel therapeutics.\n\n\nMethod\n\nWe conducted an electronic database literature search of PubMed and Google Scholar for published research articles on endometriosis and endometriotic animal models. “Endometriosis”, “endometriosis mice model”, “Primate model of endometriosis”, “endometriotic patients”, and “endometriosis-associated fibrosis” were the search terms that were employed. Articles with thorough experimental data and definitive results were considered for inclusion; those with inconclusive research findings were eliminated. We incorporated clinical trials, surveys of endometriosis-affected women, and observational and experimental studies including animal research as references. Research written in languages other than English was not considered. All the graphics were prepared using Biorender software (BioRender.com).\n\n\nLiterature review\n\nEndometriosis is characterized by the persistent occurrence of fibrosis and myofibroblasts within endometriotic lesions, which play a critical role in the disease’s development, making fibrosis a molecular hallmark of endometriosis.23 Significant scarring is commonly linked to endometriosis.23 Although the initial onset of endometriosis is associated with the existence of endometrial stromal and glands in abnormal locations, often the endometrial components are soon replaced by fibrotic and smooth muscle components.24 Rectovaginal nodules frequently display glandular epithelium embedded deeply within fibromuscular tissue, devoid of any surrounding stroma.25 Additionally, in 40% of ovarian endometriomas, there is no detection of endometrial epithelium, and the interior of the cyst is covered solely by fibrotic tissue.26 Despite being a crucial pathological feature of the disease, pelvic adhesions generally lack any endometrial components.14 These adhesions contribute to the pathology of some common symptoms of endometriosis, including chronic pelvic pain, deep dyspareunia, and infertility, which may be influenced by pelvic adhesions.14 In fibrosis of organs like lungs, liver, and kidney, involvement of TGF-β signaling pathway is well documented.27 TGF-β is an influential growth factor and a chemical that attracts monocytes and is capable of triggering fibrosis and angiogenesis in abnormal growths and promoting the advancement of endometriosis.28 In comparison to normal women, the peritoneal fluid of stage III and IV endometriosis patients exhibits greater levels of TGF-β.29 The process by which endometriosis progresses to a malignant condition remains unknown. However, continuous inflammation, immunological dysregulation, and fibrosis, most likely caused by iron-induced oxidative stress, may lead to genetic changes, which may lead to a malignant feature.30,31 Fibrosis is believed to be linked to pain, which is the disease’s most common symptom and the principal cause of the patient’s poor quality of life.32 If the underlying mechanisms are uncovered, they may explain why the disease’s morphological characteristics do not match the extent and nature of fibrosis-induced pain sensations.33 Fibrotic tissue is defined by excessive development of extracellular matrix (ECM) components inside and around inflamed or damaged tissue, and it is a typical and significant phase of tissue repair in all organs. Fibrosis involves activated platelets, macrophages, and myofibroblasts, which result in increased collagen deposition.34 Furthermore, fibrosis occurs with the transition from epithelial to mesenchymal cells in variety of malignancies, which is associated with poor prognosis.35 Fibrosis and smooth muscle metaplasia are two of the main characteristics of endometriosis in women; fibrosis is found surrounding the endometriotic tissue, and the degree of fibrosis is connected with the degree of smooth muscle metaplasia.36 Based on these data, we postulate that fibrotic-based EMTs’ involvement in chronic inflammatory responses may be a factor in the invasive nature of endometriotic lesions. Also, angiogenesis which stimulates endothelial function, vascular permeability, and the emergence of experimental endometriosis, is commonly associated with this heightened invasive and metastatic potential.37 Endometriotic lesions are thought to be “wounds” that undergo repeated tissue injury and repair (ReTIAR) through the processes of smooth muscle metaplasia (SMM), fibroblast-to-myofibroblast trans-differentiation (FMT), and epithelial-mesenchymal transition (EMT). This process ultimately leads to fibrosis and is a common feature of all endometriotic diseases.31,38 Epithelium-mesenchymal transition (EMT) is characterized by polarised, stationary epithelial cells change into highly motile mesenchymal cells.39 This makes it possible for solitary cells to pass through the basement membrane, grow invasively, and metastasize by both intra- and extravasation. Sampson’s implantation theory states that each of these occurrences is necessary for the development of an endometriotic lesion.8\n\nRegretfully, due to differences in opinion over the etiology of the disease, the EMT route has received less attention in the context of endometriosis than it does in cancer research. In recent times, most research on EMT in endometriosis focuses on tissues; very few examine the specific transcription factors involved in EMT signaling that are present in endometriotic cells.40,41 EMT-related processes in endometriosis have been reported to be much higher in ectopic endometrial lesions than in eutopic endometrium.42 As a result, endometriosis etiology may involve EMT. We speculate that EMT and fibrosis processes may be involved in the evolution of endometriosis, given its chronic nature and the possibility of it leading to fibrotic adenomyosis. Additionally, in their mouse model of endometriosis, Modi et al., discovered significant inflammation but no histological fibrosis and no epithelial-mesenchymal transition concluding EMT and fibrosis are not typical in endometriosis.43 Consequently, studies on the molecular pathways based on EMT or possible targets for therapeutic intervention for EMT and fibrosis in endometriosis were stopped due to the unavailability of a animal model of endometriosis that mimicked the human condition. Endometriosis research is mostly based on non-human primate or rodent models due to the apparent limitations and ethical concerns of human experimentation. The available mice models have aided in the investigation into several aspects of the disorder, such as early disease phases,44 steroid hormone involvement,45 host inflammatory mechanisms,46,47 oxidative stress,48,49 neuro-angiogenesis,50 and infertility51 were also studied in mice. However, there is a paucity of information on the development of pre-clinical models that define clinically effective endpoints such as fibrosis or EMT-induced metastasis. Furthermore, 50-70% of drugs that advance to phase II and III of clinical trials are unable to show efficacy.52 This suggests that there are not enough disease models to investigate crucial biological processes. To conclude, we want to highlight that an ideal animal model developed specifically to study endometriosis should include the same cellular and pathophysiological pathways and clinical behaviours that are observed in endometriotic patients, such as fibrosis leading to scar formation and EMT linked to invasion and metastasis.\n\nAccording to Greaves et al., endometriosis is currently being studied using two basic approaches: human-based in vitro samples and experimental in vivo animal models. The first type involves experimental in vitro research using tissue biopsies and fluids obtained from resected lesions or aspiration biopsies, such as endometrial and peritoneal explants, endometriotic cell lineages, primary endometrial stromal cells, endometrial stem cells, and immune cells.53 In vivo animal models are essential for assessing drug candidates and for preclinical trial testing. Our knowledge of the early phases of disease development, including the effects of peritoneal microenvironment, inflammatory responses, and steroid responsiveness has improved because to these models.54 For several reasons, it is challenging to create in vitro or in vivo models that mimic or represent the salient characteristics observed in endometriotic patients, such as EMT or fibrosis. One, the condition is multifactorial, heterogeneous complexity, as none is certain of the condition’s onset or duration. Second, there are many disease characteristics associated with endometriosis, including peritoneal, deep infiltrative lesions, and ovarian endometrioma. Lastly, endometriosis cannot be modelled based on a particular pathophysiological mechanism.55 Furthermore, endometriosis has been connected to genetic,56 immunological,57 environmental,58,59 and hormonal changes such as progesterone resistance60 and estrogen dependency61 further posing challenge in creating a suitable animal model (Figure 1).\n\nOne of the most significant obstacles in endometriosis research is the lack of reliable animal models. Ideally, a disease model should mirror human disease while also allowing researchers to investigate the effects of intrinsic (e.g., genes) and extrinsic (e.g., environment) factors on disease progression. Many previous studies linked fibrosis secondary to the development of endometriosis and there has not been much research on the study of fibrosis. Based on research from animal models of the condition, it became clear that a percentage of women receiving hormone therapy in human trials were not responding to these drugs62 requiring surgical lesion removal to alleviate symptoms. Women may have endometriotic lesions that have progressed to a fibrotic state by the time they seek medical attention, rendering treatment ineffective. Significant evidence supporting the process of fibrosis comes from in vitro experiments conducted on humans and from in vivo higher vertebrates such as baboons.\n\nDespite a recent surge in endometriosis research, the underlying pathobiology of the disease remains poorly known, implying that animal models of the disorder are crucial for future studies in this field. Non-human primates and higher vertebrates are regarded to be potential candidates for disease research due to their anatomical resemblance to human reproductive organs.63 Controlled experimental investigations on humans are limited because assessing disease prevalence and development necessitates numerous laparoscopies, which are challenging for a variety of reasons. Though endometriosis occurs spontaneously in humans, human investigations have been limited for ethical and practical reasons which is one of the primary reasons being the difficulty of studying the disease. As a result, understanding the mechanisms that cause this disease requires the use of an appropriate animal model. Endometriosis has long been investigated in both primate and non-primate animals. The spontaneous endometriosis of the baboon64–66 limitation is that baboons have vast and effective mechanisms for clearing and regenerating their peritoneum66 the rhesus monkey67,68 where limitation is the significance of peritoneal cysts in endometriosis pain and discomfort was not investigated. The cynomolgus monkey69,70 has been described, with the limitations that deep lesions were difficult to diagnose and time course changes in the condition were not investigated. Though non-human primates are an excellent model for studying endometriosis, they are expensive to maintain and are extremely sensitive to captivity. Furthermore, spontaneous endometriosis occurs at a low frequency, limiting the use of primates in research.71 However, because research facilities for primates are restricted, non-primate experimental animal species, such as mice or rats, are regarded to provide an ideal first-line technique for investigating the etiology of this mysterious disease.\n\nEvery menstrual cycle, endometriosis is characterized by the development of new lesions and the advancement of pre-existing lesions. Therefore, additional research is required to comprehend the endometriosis lesion’s natural course and their gradual development.72 There is evidence of gradual lesion clearing, but only a small number of studies using mouse models of endometriosis have studied disease induction and regression.72,73 It is unethical to perform many laparoscopies on endometriosis patients to monitor disease progression. So, longitudinal studies of lesion formation and progression can considerably increase the translational efficiency of pre-clinical model of endometriosis.72\n\nMice are the most popular experimental animal models due to their ease of gene manipulation, availability, and handling, tissue similarity in vivo, small size and large litter, which make them cost-effective, and their relatively short gestation, which allows for transgenerational examination.74 Based on the vast majority of already available research publications, two types of mice models have been successfully used to implant endometriotic lesions. The first approach involves suturing, whereby human endometriotic implants are surgically auto-transplanted into the peritoneum of immunocompromised mice.75–77 The second approach involves intraperitoneal or subcutaneous implantation of autologous uterine segments into the peritoneum of recipient mice from a syngeneic donor.50,54,78 Although there are numerous reports describing the spontaneous attachment, growth, and proliferation of endometriotic lesions, these lesions do not accurately reflect human endometriosis because they do not exhibit characteristics like chronic, persistent fibrosis for internal scarring, or invasiveness based on EMT. Moreover, the animal models provide data on the inflammatory processes generated by implanted lesions rather than those caused by endometriosis. Rats can only produce superficial lesions, which are the most fundamental and possibly least clinically significant types of lesions. The inability of any study to recreate fibrotic endometriotic lesions may account for the failure of rat models to yield data relevant to the pathophysiology and treatment of human endometriosis. This situation demonstrates that the preclinical animal studies that have been established are not transferable.79 Many studies using rodents as a model for endometriosis have looked at the gene expression patterns of ectopic tissue deposits in rats in an attempt to correlate them with human endometriotic lesions. Chronic inflammation, angiogenesis, and extracellular matrix remodeling have all been found to be common pathways.80–82 While some aspects of the disease are replicated in the rodent model, all the modifications involve suturing uterine fragments (endometrium plus myometrium) to different sites, which does not accurately represent the formation of lesions from those shed endometrial tissue or the dissemination of menstrual tissue into the peritoneum. It is noteworthy that, particularly in terms of understanding its pathophysiology and treatment options, the current rodent models have not been successful in yielding findings that apply to human endometriosis. Therefore, fibrosis a mostly disregarded component of human endometriosis be taken into consideration.83,84 However, efforts to translate the results into humans were unsuccessful in offering effective endometriosis treatments. Therefore, developing novel animal models that mirror the continuous fibrotic process seen in endometriotic patients is essential in improving our understanding of the disease. An increasing amount of research has recently brought attention to the role that fibrosis plays in clinical-grade endometriosis. On the other hand, little is known about fibrosis treatment strategies. Therefore, it is critical to develop a fibrotic mouse model of endometriosis, elucidate the regulatory processes behind fibrosis in endometriosis, and identify more precise specific biomarkers for the disease. These markers can also be utilized to find effective therapy targets and identify endometriosis in its early phases (Figure 2).\n\nTo mimic the fibrotic scarring observed in endometriosis, many endometriotic fibrotic animal models have been developed (Table 1). Furthermore, new in vivo models that use stromal cells generated from menstrual blood have been created to study endometriosis; these models show enhanced endometriotic cell migration and proliferation.60 Many cues, including estrogen stimulation, may trigger the epithelial-mesenchymal transition.85 Furthermore, estrogen-induced EMT of Ishikawa cells promotes adenomyosis.86 However, it remains still unknown how estrogen causes EMT in endometriosis at the molecular level. To prevent fluctuations in the mice’s estradiol levels during the estrous cycle, the majority of established mouse models use ovariectomized mice.87–90 As a result, the steady availability of estradiol in the circulation may help to promote lesion establishment and growth. But this makes it impossible to research how estrogen-induced EMT in endometriosis affects fertility like in women with normal circulating estrogen. Therefore, studies of endometriosis produced in intact mice call for more research on the connection between ectopic tissue and fertility.\n\nIn endometriotic lesions, it is known that TGF-β family members, Notch receptor, and bioactive sphingolipid sphingosine 1-phosphate (S1P) cause tissue fibrosis and change signaling pathways.91 It has been found that NF-κB is activated in endometriotic lesions and peritoneal macrophages, which are essential for the inflammation associated with endometriosis. It has been demonstrated that inhibiting NF-κB lowers the development and progression of endometriosis in women as well as its associated symptoms.92 Estrogen can promote the formation and dissemination of endometriosis ectopic lesions by upregulating the expression of the transcription factor Slug in ectopic endothelial cells and inducing the epithelial-mesenchymal transition.86 Fibrogenesis in endometriosis may be facilitated by aberrant Wnt/β-catenin pathway activation and reversed by blocking the Wnt/β-catenin pathway.93 TGF-β1 may stimulate the expression of N-cadherin, OCT4, and Snail in ectopic stromal cells, implying that TGF-β1 facilitates cell invasion.94 The AKT and ERK signaling pathways may work synergistically to promote the formation of deep endometriotic lesions by increasing endometriotic stromal cell proliferation in a fibrotic milieu in vitro.95\n\nBy inducing EMT and FMT in endometriotic lesions, platelet-derived TGF-β1 stimulates smooth muscle metaplasia (SMM) and fibrosis.96 Evidence suggests that EMT induces fibrogenesis in addition to increasing cellular invasiveness. For instance, TGF-β1/Smad3 signaling pathway, which is driven by platelets, is known to induce EMT and FMT in endometriotic lesions, which eventually results in SMM and fibrosis.96 Targeting TGF-β1 may be an effective strategy to prevent fibrosis and adhesion formation since endometriotic cells release TGF-β1, which induces ECM disorganisation and fibrosis in the tissues of ovarian endometriotic patients.97 Oxidative stress has been linked to the ADAM17/Notch signaling pathway and perhaps fibrosis, according to a study done on endometriosis patients.98 Furthermore, it is known that endometriotic cells of endometriomas express Smad2, Smad3, and Smad4 (as well as their phosphorylated forms), which causes fibrosis and adhesion to ovarian tissues, suggesting a role for TGF- β1/Smad signaling.97 FOXP1 uses Wnt signaling to increase fibrosis in endometriosis.99 Through their effects on tissue repair, senescence, EMT, FMT, and proliferation of fibroblasts/myofibroblasts, mutations in TP53, PTEN, ARID1A, PIK3CA, KRAS, and PPP2R1A appear to hasten the development and fibrogenesis of endometriosis.100 A significant increase was observed in the mRNA levels of α-SMA, vimentin, N-cadherin, fibronectin, PAI-1 (Serpine1), Snail, Slug, and LOX.101 Growth factors such TGF-β1, PDGF, EGF, and CTGF are released by activated platelets in lesions, facilitating fibrogenesis in endometriotic patients with deep endometriosis and ovarian endometrioma.102 NR4A1 is a novel pro-endometriotic transcription factor that accelerates the development of endometriosis.103 HOXC8 stimulates TGF-β signaling, which affects adhesion, cell proliferation, migration, and ovarian endometrioma.104 FAK intracellular non-receptor tyrosine kinase mediates a series of processes in the development of endometriosis, including cell adhesion, inflammatory response, and fibrosis signaling in patients with endometriomas.105 In ectopic ESCs derived from retrograde menstruation, PGE2/thrombin is known to induce modifications such FMT and EMT, which are linked to fibrotic changes in the lesions.41 Through EMT and FMT processes, proinflammatory substances such PGE2 and thrombin in retrograde menstrual fluid have been jointly implicated in generating endometriosis fibrosis in endometriotic patients. This suggests potential targets for treatment to mitigate fibrosis.41 Apart from the fibrotic and EMT markers, numerous processes, such as pyroptosis, NLRP3 inflammasome, and deregulation of the long noncoding RNA MALAT1 are identified to cause fibrosis in endometriotic patients.87 It has been discovered that reducing the number of lesions by targeting inflammatory molecules like IL-8 also known to reduce fibrosis and adhesions, highlighting the potential for disease-modifying therapy.106 While existing research has shed light on the genes involved, there is still a potential to uncover the intricate downstream signaling networks that govern this complex disease. As a result, sophisticated additional approaches, such as knockout models that incorporate high throughput RNA sequencing and omics methodologies should be emphasised to further validate the role and mechanism of fibrotic markers in the development of fibrosis, providing solid proof for the discovery of drugs that hinder, terminate, and reverse fibrosis progression and benefit endometriotic patients.\n\nEndometriosis is a common benign gynaecological disease with a high propensity for migration and invasion. The cell-to-cell or cell-ECM connections allow the cells to migrate, invade, and proliferate in new locations. MMPs are linked to adhesion, invasion, and the severity of endometriosis. This indicates that MMPs have a role in extracellular matrix remodeling, which is necessary for the development of ectopic endometriosis lesions.107 They are also significantly higher in the endometrial and peritoneal fluid of endometriosis patients.108,109 Matrix metalloproteinases (MMPs) are a family of enzymes that are mostly found in the endometrium’s functional layer. They are secreted by the resident immune cells and stromal fibroblasts, which facilitate the remodeling of the extracellular matrix including collagen, elastins, and other glycoproteins and endometrial disintegration during menstruation. Tissue inhibitors of matrix metalloproteinases (TIMP) are endogenous antagonists that reduce MMP overexpression, and ovarian steroid hormones are known to control MMP activity.110 For early clinical studies of EMT, the nude mouse is a suitable model, particularly for the identification of MMP-2 and TIMP-2, proteins that seem to play a significant role in the pathophysiology of EMT. It has been found that estrogen specifically increases MMP-2 expression to encourage ectopic implantation of the endometrium. Progestin, on the other hand, can suppress TIMP-2 expression, increasing the MMP-2/TIMP-2 ratio and increasing the invasiveness of ectopic endometrium to facilitate implantation.111 In ovarian endometriosis, MMP7 facilitated the epithelial-mesenchymal transition; EGF increased MMP7 expression by activating the ERK1-AP1 pathway.112,113 MMP14 affects the development and function of invadopodia, which in turn modulates mesenchymal cells’ capacity for invasion and migration.114 MMP-2 and MMP-9, two important enzymes involved in the destruction of diverse types of ECM, have been linked to the development of endometriosis by regulating endometrial cell invasion.115 MMP-2 and MMP-9 have been shown to operate as both biomarkers of EMT and triggered factors that contribute to the progression of EMT.116 As a result, we hypothesize that MMPs may be crucial in controlling the endometriosis-related EMT process. However, further research is required to fully understand the connection between MMPs and the epithelial-mesenchymal transition in endometriosis, as there are not enough comprehensive studies on the subject. Despite this, it is apparent that MMPs play a crucial role in collagen production, which is necessary for endometriosis fibrosis to develop gradually.107 These findings suggest that there may be a precise equilibrium between collagen synthesis and breakdown, which should be investigated further.\n\n\nDiscussion\n\nEndometriosis is an underdiagnosed chronic inflammatory disease that affects millions around the world. The primary explanation for endometriosis growth is the transplantation of living endometrial cells that are refluxed after menstruation, thereby attaching to and invading other pelvic organs developing inflammation and fibrosis.2 Despite its broad incidence and importance, endometriosis research has significant limitations.117 The gaps include a lack of understanding of the disease’s etiology, a delay in diagnosis that necessitates invasive treatments, and the difficulties of integrating electronic health records for research, which aids in identifying potential therapeutic tools and reminds us to look beyond endometriotic lesions.118 50 to 70 percent of endometriotic drugs that advance to phase II and III in clinical trials are unable to show efficacy, suggesting an unfulfilled research gap in developing appropriate animal models.119 Endometriosis fibrosis shares characteristics with other fibrotic conditions, including increased myofibroblast and smooth muscle cell activity, high levels of fibrotic-associated growth factor and protein production, epithelial to mesenchymal transition, and collagen deposits.15 Molecular hallmarks of endometriosis include immunological dysregulation, ER expression, progesterone resistance, chronic inflammation, angiogenesis, and epigenetic changes. There is substantial evidence that fibrosis is a molecular characteristic of endometriosis etiology.15 Interestingly, fibrosis as a histologic feature in lesions can progress, most likely due to repeated tissue injury and repair caused by inflammation-induced recurrent menstrual bleeding31,120 Thus, a thorough understanding of the disease process is required for progress in the fields of biomarker identification and nonhormonal therapy. Fibrosis may impair drug administration and efficacy. Rather, a study into the mechanisms that resolve fibrosis will uncover new possibilities by discovering new targets for pharmacologically regulating the condition, notably in the pharmacology of multi-component medications.100,121 Because EMT-induced fibrosis is numerous and diverse and plays vital functions in various human body systems, robust longitudinal studies are required to [1] Confirm biomarkers and underlying mechanisms linked with fibrosis progression, providing insights into disease causes and potential diagnostic or prognostic tools. [2] To investigate temporal dynamics to record the advancement of fibrosis over time, allowing researchers to better comprehend its development from early stages to advanced forms thereby allowing early intervention and personalised treatment methods. [3] To investigate treatment efficacy, or the effectiveness of various interventions for fibrosis, to provide useful data on long-term outcomes and responses. [4] To better understand the natural course of fibrosis, including its variations among individuals, potential triggers, and variables influencing its progression, to create preventive and targeted therapeutics. [5] To determine whether endometriosis’s inflammatory environment participates in fibrosis. The proposed pathways of endometriosis participation in fibrosis require more investigation. Indeed, discovering fibrosis-specific therapies for endometriosis remains a significant issue. As a result, further inquiry and investigation are needed in the future. Finding the underlying etiology of endometriosis is made more difficult by the disease’s missing components, such as EMT and fibrosis, which have yet to be replicated in experimental rodent models that use heterologous or homologous endometriotic tissue. Filling in these gaps may lead to more accurate patient diagnoses, more effective medications, and a better knowledge of how the disorder affects women’s lives. Any treatments that help to reduce the fibrotic aspect of the disease will have far-reaching implications for the individual, the population, and the healthcare system. These thought-provoking articles show our reliance on carefully selected animal models to advance our understanding of endometriosis. They emphasize the multisystem character of pro-inflammatory mechanisms in endometriosis, as well as the need for researchers to think beyond the endometrial lesion. As we have come to expect, no single cause can explain endometriosis. Yet these studies give us optimism that more therapeutic methods to improve the quality of life for affected people are on the way. The breakthrough in the construction of models is promising research that could have substantial beneficial consequences for patients. Translating these research findings into clinical care will undoubtedly aid in shortening the extended delay to diagnosis and understanding the epidemiological underpinnings of the condition.\n\n\nConclusion\n\nEndometriosis is a prevalent gynaecological disorder with a significant influence on female patients’ physical and emotional well-being due to its intrusive, and recurring nature. The association between endometriosis and fibrosis imbalance is poorly understood; additionally, EMT may play a role in the etiology of endometriosis through immunological regulation, pro-inflammatory cytokines, and other mechanisms. Clinical trials have shown that targeting EMT-induced fibrosis can help treat endometriosis, establishing a new research direction and theoretical foundation for the diagnosis and treatment of fibrotic endometriotic patients. Thus, it is vital to examine the molecular pathways that drive and sustain fibrosis in endometriosis using a novel fibrotic-based animal model, to discover new pharmacological targets and provide creative therapeutics for patients. Furthermore, the research connecting endometriosis and fibrosis has added a further complicating factor to the shared strategy for dealing with endometriotic patients with infertility, as well as a potentially essential concern in the counselling and management of the condition for those desiring future fertility. Well-designed longitudinal studies are needed to improve clinical decision-making in these contexts. Although gynecologic surgeons are aware of the complex role of fibrosis in the surgical treatment of endometriosis, the molecular pathways that relate fibrosis to endometriosis-associated pain and infertility remain unknown. More research is needed to better understand the clinical implications of fibrosis and identify it as a molecular marker of endometriosis etiology. A potentially important element to consider while counselling and managing endometriotic patients who plan to have children in the future. Well-designed longitudinal studies are required to make more informed clinical decisions in these contexts. Efforts should be focused on building trustworthy disease models that incorporate physiologically relevant cells, such as organoids and microfluidics. The continued creation of animal models to aid in understanding the processes of endometriosis development offers the best chance of creating therapeutic options to prevent or reverse this mysterious disease. This review aims to spark a debate on the need to revise present understandings by focusing on the fibrotic features of endometriosis pathogenesis. We believe that this approach will shed new light on the condition and suggest areas that need to be investigated further.",
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PubMed Abstract | Publisher Full Text | Free Full Text\n\nProtopapas A, Markaki S, Mitsis T, et al.: Immunohistochemical expression of matrix metalloproteinases, their tissue inhibitors, and cathepsin-D in ovarian endometriosis: correlation with severity of disease. Fertil Steril. 2010 Nov; 94(6): 2470–2472. PubMed Abstract | Publisher Full Text\n\nSotnikova NY, Antsiferova YS, Posiseeva LV, et al.: Mechanisms regulating invasiveness and growth of endometriosis lesions in rat experimental model and in humans. Fertil Steril. 2010 May 15; 93(8): 2701–2705. PubMed Abstract | Publisher Full Text\n\nRydlova M, Holubec L, Ludvikova M, et al.: Biological activity and clinical implications of the matrix metalloproteinases. Anticancer Res. 2008; 28(2B): 1389–1397. PubMed Abstract\n\nWang J, Ma X: Effects of estrogen and progestin on expression of MMP-2 and TIMP-2 in a nude mouse model of endometriosis. Clin Exp Obstet Gynecol. 2012; 39(2): 229–233. PubMed Abstract\n\nChatterjee K, Jana S, DasMahapatra P, et al.: EGFR-mediated matrix metalloproteinase-7 up-regulation promotes epithelial-mesenchymal transition via ERK1-AP1 axis during ovarian endometriosis progression. FASEB J Off Publ Fed Am Soc Exp Biol. 2018 Aug; 32(8): 4560–4572. Publisher Full Text\n\nLiu F, Zhou J, Zhang X, et al.: Whole-exome sequencing and functional validation reveal a rare missense variant in MMP7 that confers ovarian endometriosis risk. Hum Mol Genet. 2022 Aug 17; 31(15): 2595–2605. PubMed Abstract | Publisher Full Text\n\nKaramanou K, Franchi M, Vynios D, et al.: Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: Lumican a key regulator. Semin Cancer Biol. 2020 May; 62: 125–133. PubMed Abstract | Publisher Full Text\n\nXin L, Hou Q, Xiong QI, et al.: Association between matrix metalloproteinase-2 and matrix metalloproteinase-9 polymorphisms and endometriosis: A systematic review and meta-analysis. Biomed Rep. 2015 Jul; 3(4): 559–565. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOrlichenko LS, Radisky DC: Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development. Clin Exp Metastasis. 2008; 25(6): 593–600. Publisher Full Text\n\nEllis K, Munro D, Clarke J: Endometriosis Is Undervalued: A Call to Action. Front Glob Womens Health. 2022 May 10; 3: 902371. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPenrod N, Okeh C, Velez Edwards DR, et al.: Leveraging electronic health record data for endometriosis research. Front Digit Health. 2023; 5: 1150687. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKimmelman J, Federico C: Consider drug efficacy before first-in-human trials. Nature. 2017 Jan 30; 542(7639): 25–27. Publisher Full Text\n\nCousins FL, Kirkwood PM, Murray AA, et al.: Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation. FASEB J Off Publ Fed Am Soc Exp Biol. 2016 Aug; 30(8): 2802–2811. Publisher Full Text\n\nLi X, Zhu L, Wang B, et al.: Drugs and Targets in Fibrosis. Front Pharmacol. 2017; 8: 855. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "311329",
"date": "22 Aug 2024",
"name": "Jae-Wook Jeong",
"expertise": [
"Reviewer Expertise Endometriosis",
"Translational study",
"Preclinical animal model"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nOverall Rating: Average Reviewer Opinion: Major Revision\nThe manuscript effectively emphasizes the significance of understanding endometriosis-related fibrosis and the limitations of current treatments. It underscores the need for better models and addresses the challenges in understanding the disease's pathogenesis. However, the presentation would benefit from a more structured approach and a clearer focus on specific research gaps and proposed solutions. Adding details on how the review addresses these gaps and improves therapeutic strategies would enhance its impact. While the review offers valuable insights into fibrotic models and treatments, greater clarity on its specific contributions is needed.\n\nAbstract: The abstract effectively outlines the importance of fibrosis research in endometriosis. Restructuring for clarity and adding specific research gaps and proposed solutions would strengthen overall outlook. Introduction:\nLink to Fibrosis: The introduction does not clearly connect endometriosis issues to fibrosis. Adding specifics on how the review addresses this would improve its rationale. Redundancy: The introduction repeats information on endometriosis mechanisms and diagnostic challenges. Reducing repetition would improve clarity.\n\nLiterature Review:\nFibrotic Endometriosis Overview: The discussion on animal model limitations could be more focused. Highlighting specific shortcomings, especially in fibrosis and EMT representation, would provide clearer insights. There is a mouse model for endometriosis and fibrosis (PMID: 30626716). Endometriotic Models: While the challenges of developing accurate models are discussed, more specific examples would be beneficial. Consider adding key limitations of rodent models and clarifying how estrogen-induced EMT impacts translation to human disease. EMT and MMPs in Endometriosis: The discussion on MMPs and EMT lacks detailed mechanisms and direct evidence. Emphasizing experimental findings and strengthening the link between MMPs, EMT, and disease progression would improve this section.\n\nDiscussion: While acknowledging the importance of translating research into clinical care, the section lacks concrete examples of how this might occur or what specific therapeutic advancements are expected. Conclusion: The call for longitudinal studies is important, but the section does not address the obstacles in conducting these studies.\n\nMinor Abstract: the first sentence: “estrogen-dependent” repeated word mesenchymal to epithelial transition (FMT) change to “MET”\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": [
{
"c_id": "12445",
"date": "02 Oct 2024",
"name": "Rahul Dutta",
"role": "Author Response",
"response": "Dear Mr. Reviewer, We are thankful to you for the constructive feedback. We have incorporated the suggested improvement into the revised manuscript. Here are the specific responses to the comments/suggestions- Abstract: The abstract effectively outlines the importance of fibrosis research in endometriosis. Restructuring for clarity and adding specific research gaps and proposed solutions would strengthen overall outlook. The abstract has been modified as advised Introduction: Link to Fibrosis: The introduction does not clearly connect endometriosis issues to fibrosis. Adding specifics on how the review addresses this would improve its rationale.- The introduction has been modified as advised Redundancy: The introduction repeats information on endometriosis mechanisms and diagnostic challenges. Reducing repetition would improve clarity. The redundant portion has been edited as advised Minor Abstract: the first sentence: “estrogen-dependent” repeated word- Removed mesenchymal to epithelial transition (FMT) change to “MET”- Changed Literature Review: Fibrotic Endometriosis Overview: The discussion on animal model limitations could be more focused. Highlighting specific shortcomings, especially in fibrosis and EMT representation, would provide clearer insights. The overview has been modified as advised There is a mouse model for endometriosis and fibrosis (PMID: 30626716). But it is developed in Baboon, what we are trying to discuss here is the fibrotic mice model Endometriotic Models: While the challenges of developing accurate models are discussed, more specific examples would be beneficial. Consider adding key limitations of rodent models and clarifying how estrogen-induced EMT impacts translation to human disease. Modified as advised EMT and MMPs in Endometriosis: The discussion on MMPs and EMT lacks detailed mechanisms and direct evidence. Emphasizing experimental findings and strengthening the link between MMPs, EMT, and disease progression would improve this section. Modified as advised We extend our heartfelt gratitude for the feedback."
}
]
}
] | 1
|
https://f1000research.com/articles/13-721
|
https://f1000research.com/articles/13-1461/v1
|
02 Dec 24
|
{
"type": "Research Article",
"title": "New Approaches of Generalised Fuzzy Soft sets on fuzzy Codes and Its Properties on Decision-Makings",
"authors": [
"Masresha Wassie Woldie",
"Jejaw Demamu Mebrat",
"Mihret Alamneh Taye",
"Jejaw Demamu Mebrat",
"Mihret Alamneh Taye"
],
"abstract": "Background Several scholars defined the concepts of fuzzy soft set theory and their application on decision-making problem. Based on this concept, researchers defined the generalised fuzzy soft set and its applications. However, to the best of the author’s knowledge, the generalised fuzzy soft set has not been dealing with in the generalised fuzzy soft code set. In this paper, we introduce the notion of generalised fuzzy soft code set and its application.\n\nMethods The theory of fuzzy soft sets and its application, generalised fuzzy soft sets and fuzzy codes in different years were studied with various researchers. To derive a generalised fuzzy soft code set, we apply the concepts of generalised fuzzy soft set and a new view of fuzzy codes and its application. A new aspect of this paper is to introduce the definition of generalised fuzzy soft code sets and its application on medical diagnosis and decision-makings.\n\nResults Generalised fuzzy soft code is the most powerful and effective extension of fuzzy soft sets that deal with the choice’s parameterized values. It is an extended model of fuzzy soft sets and a new mathematical tool with significant advantages for handling uncertain information and is proposed by combining the concept of fuzzy soft sets and fuzzy code sets. This paper introduces the concept of generalised fuzzy soft code and its properties.\n\nConclusions In this study, we combine generalised fuzzy soft set and a different approach to coding theory to introduce generalisation of fuzzy soft codes. The paper also considers the relation between generalised fuzzy soft code and its application. We discussed the matrix representation of generalised fuzzy soft code. Furthermore, a demonstration example illustrates how the strategy could be effectively applied to various problems.",
"keywords": [
"Fuzzy Soft set",
"Fuzzy code",
"interval-valued fuzzy soft code",
"generalised fuzzy soft set",
"Generalised fuzzy soft code."
],
"content": "1. Introduction\n\nZadeh (1965) established the notion of a “fuzzy set” as a way to represent a class of objects with different membership grades. A membership function, also known as a characteristic function, describes such a set, with each item’s membership degree ranging from 0 to 1. Molodtsov (1999) presented the theory of soft sets as a novel mathematical technique for handling uncertainties that are outside the scope of current mathematical techniques. In order to address complicated issues including ambiguity and uncertainty, Molodtsov created a universal mathematical tool that may be applied to both conventional and some modern mathematical methods. Fuzzy sets are conceptualized in a way that makes their methods intuitively clear. Maji, Biswas, and Roy (2003) developed the theory of soft sets. Gogoi, Kr. Dutta, and Chutia (2014) introduced an application of fuzzy soft set theory in day to day problems; Roy and Maji (2007) presented the application of fuzzy soft set theory to decision-making problems. Amudhambigai and Neeraja (2019) discussed a new view of fuzzy codes and its application. Ozkan and Mehmet (2002) introduced different approaches of fuzzy codes and their properties. Malik, Mordeson, and Nair (1992) defined the concept of a fuzzy generating set and describe the fuzzy subgroup which it generates and introduced the notion of a minimal fuzzy generating set. Ali et al. (2018) designed and develop a new class of linear algebraic codes defined as soft linear algebraic codes using soft sets. They also discussed some algebraic properties of soft codes. Garg and Arora (2018) describe the concept of generalized IFSS. Kong, Wang, and Wu (2011) studied the implementation of grey theory-based fuzzy soft sets in decision-making situations. Lin et al. (2018) a set of code words from the cyclic code are decoded using a binary parity-check matrix in a soft-joint manner. Gereme, Demamu, and Alaba (2023), Hamming distance of fuzzy codes and other features of binary fuzzy codes. (Lin et al. 2018) a novel coding technique for the Galois-Fourier transform domain that is intended for collective encoding and collective iterative soft-decision decoding of cyclic codes of prime lengths. Kamble (2017) examined the codes that emerged from soft sets and fuzzy sets, and using fuzzy linear space, explained the properties of fuzzy linear codes. Kim (2023) developed a fuzzy linear code description based on linear algebraic codes. Tsafack et al. (2018) established the concepts of fuzzy cyclic and linear codes over a Galois ring. Majumdar and Samanta (2010) established generalized fuzzy soft sets and investigated a few of their characteristics. It has been demonstrated that generalized fuzzy soft sets can be used to diagnose medical conditions and decision-making problem. Adde, Toro, and Jego (2012) examined linear block code of maximum likelihood soft-decision decoding. Dauda, Mamat, and Waziri (2015) an application of fuzzy soft sets based on a thorough theoretical analysis of the fundamental operations of soft sets and a definition of soft sets. Kané (2021) suggested a different method for figuring out the fuzzy optimal solution to a semi-fully fuzzy linear programming issue. Ali et al. (2023) discussed the generalized intuitionistic decision-theoretic rough set, a combination of intuitionistic fuzzy sets and decision-theoretic rough sets.\n\nHowever, as far as the author’s awared, no studied pertaining to the fundamentals of generalised fuzzy soft code have been released. Thus, motivated by the formationed works, the current study seeks to introduce this idea. To derive a generalised fuzzy soft code and its properties, we integrate the concepts of a generalised fuzzy soft set (Majumdar and Samanta 2010) and a different approaches of coding theory (Ozkan & Mehmet 2002). A new aspect of this paper is to introduce and develop the definition and application of generalised fuzzy soft code by combining the concepts of fuzzy soft set and fuzzy codes. The definition and features of relations on generalised fuzzy soft codes are proposed.\n\nThe organization of this study as follows: Section 2 included fundamental notions and properties of preliminary concepts, Section 3, Generalised fuzzy soft code, and some of their characteristics, whereas, Section 4 takes into consider relation on generalised fuzzy soft codes and its application.\n\n\n2 Methods\n\nIn this section, we review a few fundamental concepts that we utilize to get our outcomes.\n\nOzkan & Mehmet (2002) The notion Fq=(a1,a2,…,aq), is a q-ary code which is a collection of symbol sequences in which each symbol is chosen from a set of q different components. The set Fq is sometimes referred to as the alphabet and is defined as the set\n\n(Amudhambigai & Neeraja 2019) Fn is the collection of all ordered n− tuples\n\np=p1,p2,…,pk, Where each p i in Fq . The elements of Fn are referred to as words or vectors.\n\nOzkan & Mehmet (2002) Let us assume that C has a as a code word. The relative weight of a code word a, denoted as\n\nRw(a) , is the sum of p1,p2,…,pk if p1,p2,…,pk are defined as the positions of 1s in a . For instance, Rw(a)=1+3+4+5=13 if a=10111 is a code word of C in F5 .\n\n1+2+3+…+n is the relative weight of 111…1, which is a code word of C in F2n . This can be articulated as the sum of the first n positive integers. The largest relative weight of code C in F2n is referred to as this matter. Where n is the length of a code word, where Rwr is a mapping defined as Rwr:C→[0,1] for C ∈ F2n and Rwr(a)∈[0,1], for any a∈C .\n\n(Ozkan & Mehmet 2002) Let {c1,c2,…,cn} is the code word of C with length n. Let C be a code.\n\nFor each i=1,2,…,n, let Rwr(ci) be a fuzzy code word related to the code words ci , cj in C . Then the fuzzy code intersection and union of any two fuzzy codes Rwr(ci) and Rwr(cj) , respectively, are given as follows:\n\n(Amudhambigai and Neeraja 2019) For any fuzzy code Rwr(ci) , the complement is c(Rwr(ci)) is calculated by subtracting from 1 the relative weight of each member of C .\n\nThat is,\n\n(Kong, Wang, and Wu 2011) Consider the idea of a set of parameters represented by E and U be the notion of a starting universe of items. P(U) be represents the power set of U and A⊆E . A pair (F,A) is a soft set over U if and only if F is a mapping given by\n\nIn other words, the soft set is a parameterized family of subjects from the set U.\n\nConsider the set of e elements of the set (F,A) , or the set of e− approximate components of the soft set, where F(e) can be arbitrary, some of which can have nonempty intersection, and some of which can be empty. This applies to every F (e) from this family for e in A . where the attributes, traits, or properties of objects are usually the arguments. We might consider Zadeh’s fuzzy set as a subset of the soft set. Given a fuzzy set A , its membership function is μA , that is, μ A is a mapping from U into [0,1], that is\n\n(Majumdar & Samanta, 2010) The set of all fuzzy subsets within a universal set U is denoted by IU .\n\nAssume A⊆E and that E is a parameter set. Then, a pair (F,A) is a fuzzy soft set over U , where F is a mapping denoted by\n\n(Ali et al. 2018) Assume that a vector space of size n over the field K is represented by W=Kn . (F,E) is as of t algebraic linear code over K . For every F(ei);1≤i≤t , the symbol F(E)=F(e1),…,F(et) in x indicates a linear algebraic code of W . The number of linearly independent elements of F(ei) is denoted by di, which is the dimension of F(ei) . Each F(ei)∈F(E) in this instance represents a linear algebraic code. The soft dimension of (F,E) is (F,E)={d1,d2…,dt} and the number of soft code words of (F,E) is given by:\n\nWhere 1≤i≤t .\n\nKeep in mind that dim(F,A) represents the soft dimension (F,E) .\n\n(Majumdar & Samanta 2010). The universal set of elements is ={x1,x2,…,xn} , and the universal set of parameters is\n\nE={e1,e2,…,em}. We shall refer to the pair (U,E) as a soft universe. Let μ be a fuzzy subset of E , that is,\n\nμ:E→[0,1], and let F:E→IU .\n\nwhere the set of all fuzzy subsets of U is represented by IU . Assume that Fμ represents the mapping. Let a function Fμ such that\n\nFμ:E→IU×I have the following definition:\n\nFμ(e)= F(e),μ(e)) , where (e)∈IU .\n\nA generalised fuzzy soft set (in short GFSS) over the soft universe (U,E) is then denoted by Fμ . Here, for every parameter ei , Fμ(ei)=(F(ei),μ(ei)) showed both the degree of belongingness that μ(ei) represents and the degree of belongingness of the elements of U in F(ei).\n\n(Majumdar & Samanta 2010) Let Fμ and Gσ be two generalised fuzzy soft sets over (U,E). Now Fμ is said to be a generalised fuzzy soft subset of Gσ if\n\n(i) μ⊆σ\n\n(ii) F(e)⊆G(e) , for all e∈E , in this case we write F(e) is a fuzzy subset of G(e) .\n\n(Majumdar and Samanta 2010) Consider a generalised fuzzy soft set over (U,E) , denoted by Fμ . Then, F∁ represents the complement of Fμ , which is defined as\n\nσ(e)=μ∁(e), for all e∈E .\n\n(Majumdar & Samanta 2010) Fμ⋃Gσ represents the union of two generalised fuzzy soft sets Fμ and Gσ . This results in a generalised fuzzy soft set Hν , which is defined as Hν:E→IU×I such that Hν(e)=(H(e),ν(e)) where H(e)=F(e)°G(e),ν(e)=μ(e)°σ(e), and ° denotes a t-norm.\n\n(Majumdar & Samanta 2010) Fμ⋃Gσ represents the intersection of two generalised fuzzy soft sets, Fμ and Gσ . This leads to a generalised fuzzy soft set Hν , which is defined as\n\nHν:E→IU×I such that Hν(e)=(H(e),ν(e)) , where ∗ is a t-co norm and\n\n(Majumdar & Samanta 2010) ∅θ:E→IU×I indicates a generalised null fuzzy soft set, which is referred to as a generalised fuzzy soft set, such that ∅θ(e)=(F(e),θ(e)), where ∅(e)=0¯ , and θ(e)=0 , for all e∈E .\n\n(Majumdar & Samanta 2010) A generalised absolute fuzzy soft set, represented by\n\nAα:E→IU×I, is refered to as a generalised fuzzy soft set, where\n\nAα(e)=F(e),α(e) is defined by A(e)=1¯, and α(e)=1 , for all e∈E .\n\n\n3. Results\n\nIn this subsection, we introduce generalised fuzzy soft codes and its properties.\n\nLet U=Rwr(ai) for which C is the universal element, consider the set of parameters be E, and ai is an element of a code vector. The fuzzy soft code universe is a pair (F,E).\n\nLet F:E→P(Rwr(ai)), where all fuzzy code subsets of Rwr(ai)∈[0,1] are collected as P(Rwr(ai)) . And consider a mapping μ and Fμ such that\n\nis a fuzzy subset of E and\n\n(Rwr(ai),E).μ(ei) is a representation of the possibility of membership, and the degree of belongingness of Rwr(ai)∈F(ei) is indicated for each parameter ei by Fμ(ei)=(F(ei),μ(ei)).\n\nConsider C⊆F24 and let\n\n={0.2,0.5,0.8,0.6,0.4,0.9,0.3,1} be a fuzzy code of the eight computers under consideration.\n\nLet E={e1,e2,e3,e4} be the set of qualities of the given computers, where the symbols e1 denote a super computer, e2 a micro computer, e3 a workstation computer,and e4 a personal computer.\n\nLet μ:E→Rwr(ai)×[0,1] = [0, 1] be a fuzzy code subset defined as follows:\n\nAnd we define a function\n\nFμ:E→P(Rwr(ai))×Rwr(ai) , be defined as follows:\n\nA Generalised fuzzy soft code over (Rwr(a),E) is then Fμ .\n\nThis can be represented in matrix form as follows:\n\nThe GFSC is then can be defined as\n\nFμ(ei),(ei)=(F(ei),μ(ei)),∀e∈E,F(e)∈P(Rwr(ai)) and ∀i .\n\nGiven two GFSCs over (Rwr(a),E), let Fμ and Gσ . Specifically, Fμ is a subset of Gσ that is considered a generalised fuzzy soft code if\n\ni μ⊆σ\n\nii F(e)⊆G(e),∀e∈E\n\nHere, we compose Fμ⊆Gσ.\n\nThe GFSC Fμ over (Rwr(a),E) is the one presented in example 3.12. Let Gσ be an additional GFSC defined as follows over (Rwr(a),E).\n\nHere σ and Rwr(a) are the respective mapping given by\n\nThen, a generalised fuzzy soft code subset of Gσ is Fμ .\n\nMatrix representation of Gσ is given by\n\n(Intersection of GFSC). Fμ⋂Gσ represents the GFSC intersection of two GFSCs of Fμ and Gσ over (Rwr(a),E) , and is defined as\n\n(Union of GFSC) Fμ⋃Gσ represents the GFSC union of two GFSCs of Fμ and Gσ over a soft universe (Rwr(a),E) , and is defined as\n\n(Complement of GFSC). The following notation represents the complement of the GFSC of Fμ:(Fμ)∁ or Subtracting the GFSC of each member of (Fμ(e),μ(e)) from 1 yield F∁μ∁ . That is,\n\nIf Fμ and Gσ represent any GFSC over a shared soft universe (Rwr(a),E) , then the following result is hold:\n\n(i) Fμ=Fμ⋂Fμ\n\n(ii) Fμ=Fμ⋃Fμ\n\n(iii) (F∁μ∁)∁=Fμ\n\n(i) (Fμ⋂Gσ)∁=F∁μ∁⋃G∁μ∁\n\n(ii) (Fμ⋃Gσ)∁=F∁μ∁⋂G∁μ∁\n\nThe proof follows directly from the definition.\n\nThe following properties are hold, if (F,A) and (G,B) are two generalised fuzzy soft codes over the common universe Rwr(a).\n\n(i) ((F,A)⋃(G,B))∁=(F,A)∁⋂(G,B)∁\n\n(ii) ((F,A)⋂(G,B))∁=(F,A)∁⋃(G,B)∁\n\n\n\n(i) ((F,A)⋃(G,B))∁=(F∁,¬A)⋂(G∁,¬B)=(H∁,¬A׬B),\n\nwhere H(¬e,¬e′)=F∁(e)⋃G∁(e′)=(H,¬(A×B)))\n\nAssume that, ((F,A)⋂(G,B))=(H,A×B))\n\nThus, from our discussion we get the result,\n\nThe proof of (ii) is similar to the above.\n\nA generalised null fuzzy soft code, represented by Fμ, is considered to be a generalised null fuzzy soft code if\n\nFμ:E→P(Rwr(a))×Rwr(a) and Fμ(e)=(F(e),μ(e)), where F(e)=0¯ and μ(e)=0,∀e∈E.\n\nA GFSC is said to be a generalised absolute fuzzy soft code, denoted by Gσ if Gσ:E→P(Rwr(a))×Rwr(a), where Gσ(e)=(G(e),σ(e)) is defined by G(e)=1¯,∀e∈E, and σ(e)=1∀e∈E.\n\nGiven any GFSC over (Rwr(a),E) , let’s say Fμ . The generalised null fuzzy soft code and generalised absolute fuzzy soft code over (Rwr(a),E) denoted as Gσ and Hθ , respectively. Then, thefollowing result is hold:\n\n(i) Fμ⋂Gσ=Gσ\n\n(ii) Fμ⋂Hθ=Fμ\n\n(iii) Fμ⋃Gσ=Fμ\n\n(iv) Fμ⋃Hθ=Hθ\n\n(v) Gσ⋃Hθ=Hθ\n\n(vi) Gσ⋂Hθ=Gσ\n\n(i) Let Fμ be any GFSC over (Rwr(a),E) and let Gσ be the generalised null fuzzy soft code over\n\n(Rwr(a),E) . Then\n\n(ii-v) Similar to the proof of (i)\n\nGiven a universal set U=Rwr(a), consider two generalised fuzzy soft codes over Rwr(a):(F,A) and (G,B) . Then, the addition operation modulo between (F,A) and (G,B) is represented by (F,A)⊕(G,B), and the multiplication operation modulo between (F,A) and (G,B) is represented by (F,A)⊙(G,B) . The interpretationof these notations are as follows:\n\n( F,A)⊕(G,B)=(H,a×b), where\n\n(F,A)⊙(G,B)=(H,a×b) , where\n\n(H,a×b)=F(a)⋂G(b) and a×b∈A×B.\n\n\n4. Relation on generalised fuzzy soft code and its application\n\n\n\nConsider the generalised fuzzy soft codes (F,A),(G,B), and (H,C) over the common universe Rwr(a) . That, the following characteristics are held:\n\n(i) ((F,A)⊕(F,A))=(F,A)\n\n(ii) ((F,A)⊙(F,A))=(F,A).\n\nFrom the definition, the argument is obvious.\n\nOver the parameterized universe (Rwr(a),E) . and A⊆E2 , let Fμ and Gπ be two GFSC. A fuzzy soft code relation R between Fμ and Gπ is a function that looks like the following:\n\ncharacterized as\n\nLet F={Fμii,i∈I}, as any collection of GFSC over (Rwr(a),E) and A⊆En , where I is the index set. The mapping R:A→P(Rwr(a))×Rwr(a) is then a n− ary generalised fuzzy soft code relation R on F , defined by R(ei1,ei2,ei3,…,ein)=min{Fμi1i1(ei1),Fμi2i2(ei2),…,Fμinin(ein)},where(ei1,ei2,ei3,…,ein)∈A.\n\nThe following illustrates how this generalized fuzzy soft code relation is used in a decision-making problem. Assume there are four computers in the universal set\n\nU={c1,c2,c3,c4} and there are four parameters E={e1,e2,e3,e4} which characterize their performance regarding a certain task. Assume a company wishes to purchase one of these computers based on certain criteria. Let there are two observations Fμ and Gσ by two experts A and B respectively\n\nLet the membership matrices that correspond to them be as follows:\n\nLet R:A→P(Rwr(a))×Rwr(a), be the generalised fuzzy soft code relation between Fμ and Gσ , defined as follows:\n\nIn order to identify the optimal computer, we first identify the greatest numerical grade indicated by the parenthesis in each column, with the exception of the final row, which represents the computer’s grade of belongingness in relation to each set of parameters. Now, the total of the products of these numerical grades with the associated values of λ is used to calculate each of these computers’ scores. That is the desired computer, the one with the greatest score. We do not take into account the computers’ numerical grades in relation to the pair (ei,ei),i=1,2,3,4, as both the parameters are same.\n\nHence, score (c1)=0.8∗0.6+0.6∗0.3=0.66,\n\nscore (c2)=0.6∗0.6=0.36,\n\nscore (c3)=0.6∗0.5+0.6∗0.3+0.5∗0.5+0.8∗0.3=0.97,\n\nscore (c4)=1∗0.3+0.9∗0.3+1∗0.8+1∗0.3=1.67\n\nThe company will then choose the computer that scored the highest, and they will purchase that computer c4.\n\n\n5. Conclusion\n\nIn this study, we have presented a Generalised fuzzy soft set and a New view of fuzzy codes and its application to introduce the new concept of Generalised fuzzy soft code and its characteristics. In fact, in this study, we introduced binary fuzzy soft code and its properties, and an application of Generalised fuzzy soft code has been presented. This study will serve as an introduction for future researchers who will work in this area. Furthermore, we can develop the study of Generalised interval-valued fuzzy soft codes; generalised intuitionistic fuzzy soft codes; Generalised interval-valued intuitionistic fuzzy soft codes and other related topics, are possible in future works.\n\n\nConsent to participate and ethics approval\n\nThis research paper is an original work that has not been published or submitted elsewhere at the same time.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nReferences\n\nAdde P, Toro DG, Jego C: Design of an Efficient Maximum Likelihood Soft Decoder for Systematic Short Block Codes. IEEE Trans. Signal Process. 2012; 60(7): 3914–3919. Publisher Full Text\n\nAli M, et al.: New Soft Set Based Class of Linear Algebraic Codes. Symmetry. 2018; 10(10). Publisher Full Text\n\nAli W, et al.: An Improved Intuitionistic Fuzzy Decision-Theoretic Rough Set Model and Its Application. Axioms. 2023; 12(11): 1003. Publisher Full Text\n\nAmudhambigai B, Neeraja A: A New View on Fuzzy Codes and Its Application. Jordan J. Math. Stat. 2019; 12(4): 455–471.\n\nDauda MK, Mamat M, Waziri MY: An Application of Soft Set in Decision Making. Jurnal Teknologi. 2015; 77(13): 119–122. Publisher Full Text\n\nGarg H, Arora R: Generalized and Group-Based Generalized Intuitionistic Fuzzy Soft Sets with Applications in Decision-Making. Appl. Intell. 2018; 48(2): 343–356. Publisher Full Text\n\nGereme MM, Demamu J, Alaba BA: Binary Fuzzy Codes and Some Properties of Hamming Distance of Fuzzy Codes. Fuzzy Inf. Eng. 2023; 15(1): 26–35. Publisher Full Text\n\nGogoi K, Dutta AK, Chutia C: Application of Fuzzy Soft Set Theory in Day to Day Problems. Int. J. Comput. Appl. 2014; 85(7): 27–31. Publisher Full Text\n\nKamble AJ: On Construction of Codes by Using Fuzzy Sets and Soft Sets. Int. J. Math. Trends Technol. 2017; 47(3): 180–184. Publisher Full Text\n\nKané L: International Journal of Research in Industrial Engineering Paper Type: Review Paper Solving Semi-Fully Fuzzy Linear Programming Problems. Int. J. Res. Ind. Eng. 2021; 10(3): 251–275.\n\nKim J-l: Fuzzy Linear Codes Based on Nested Linear Codes. cs IT. 2023; 467: 108523–108565. Publisher Full Text\n\nKong Z, Wang L, Wu Z: Application of Fuzzy Soft Set in Decision Making Problems Based on Grey Theory. J. Comput. Appl. Math. 2011; 236(6): 1521–1530. Publisher Full Text\n\nLin S, Abdel-Ghaffar K, Li J, et al.: Collective Encoding and Iterative Soft-Decision Decoding of Cyclic Codes of Prime Lengths in Galois-Fourier Transform Domain. International Symposium on Turbo Codes and Iterative Information Processing, ISTC. 2018-Decem; 2018(1): 1–8.\n\nMaji PK, Biswas R, Roy AR: Soft Set Theory. Comput. Math. Appl. 2003; 45(4–5): 555–562. Publisher Full Text\n\nMajumdar P, Samanta SK: Generalised Fuzzy Soft Sets. Comput. Math. Appl. 2010; 59(4): 1425–1432. Publisher Full Text\n\nMalik DS, Mordeson JN, Nair PS: Fuzzy Generators and Fuzzy Direct Sums of Abelian Groups. Fuzzy Sets Syst. 1992; 50(2): 193–199. Publisher Full Text\n\nMolodtsov D: Soft Set Theory First ResultS. Comput. Math. Appl. 1999; 37: 19–31. Publisher Full Text\n\nOzkan A, Mehmet EM: Different Aproach to Codind Theory.Pdf. Pak. J. Appl. Sci. 2002; 2(11): 1032–1033.\n\nRoy AR, Maji PK: A Fuzzy Soft Set Theoretic Approach to Decision Making Problems. J. Comput. Appl. Math. 2007; 203: 412–418. Publisher Full Text\n\nTsafack S, Atamewoue S, Ndjeya LS, et al.: Fuzzy Linear Codes. Fuzzy Inf. Eng. 2018; 10(4): 418–434. Publisher Full Text\n\nZadeh LA: Zadeh_FuzzySet Theory_1965.Pdf. Inf. Control. 1965; 8: 338–353. Publisher Full Text"
}
|
[
{
"id": "346175",
"date": "03 Jan 2025",
"name": "Tahir Mahmood",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper \"New Approaches of Generalised Fuzzy Soft sets on fuzzy Codes and Its Properties on Decision-Makings \" aims to develop a decision-making approach based on generalized fuzzy soft sets. The subject of the paper fits the aims and scope of the Journal. More detailed comments are as follows and I recommend the following major revision.\nRevise the title as “New Approaches of Generalized Fuzzy Soft Sets on Fuzzy Codes and Its Applications in Decision-Makings” The abstract is not written well. It has a lot of unexplained abbreviations. The authors didn’t adequately introduce the topic they are covering in the paper. It lacks an Information Classification: General adequate background of the problem highlighting the motivation for the study, main results, and conclusions. Further it is too short. Keywords are not enough to understand the theme of the manuscript. These should be enhanced. Most of what is currently Introduction should be moved from another section or should be extended, since it is too short to be useful and it should deal with the background of the problem and literature review effectively. Within this section, the authors should highlight the research gaps that this paper is trying to cover. The authors should discuss in the introduction a short overview of the problem and highlight the purpose and the aim of the study, as well as the main results, conclusions, and scientific contributions. It also lacks the historical background and literature review of the proposed study including the framework of soft set. The paper does not have a proper discussion. The authors did not discuss how the results can be interpreted from the perspective of previous studies. Discussion should clearly and concisely explain the significance of the obtained results to demonstrate the actual contribution of the article to this field of research when compared with the existing and studied literature. In the manuscript all the references should be cited correctly. For Example, in Definition 6, the reference (Kong, Wang, and Wu 2011) is cited, which needs correction. In subsection 3.1 and hence in the whole manuscript “generalised” should be “generalized”. The authors didn’t explain the limitations and implications of the proposed approach. Applications of the proposed theory needs attention as it is not properly treated. The conclusion is scarce. The authors should address the main research questions and highlight the main results, conclusions, contributions, and future research directions in the conclusion. Future scope of research should be multidirectional like bipolar soft sets, double framed soft sets, soft algebraic structures etc. English writing should be improved, particularly regarding syntax and style errors. Information Classification: General To address the above mentioned issues regarding literature review and future scope of the proposed study authors must add and cite some recent and well related manuscripts by Ashraf ul Quran, Tahir Mahmood and Muhammad Akram.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1461
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https://f1000research.com/articles/13-1103/v1
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27 Sep 24
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{
"type": "Brief Report",
"title": "Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator and a pilot study in orthopaedic-trauma patients.",
"authors": [
"Theodosios Saranteas",
"Eleni Poulogiannopoulou",
"Maria Riga",
"Konstantina Panagouli",
"Andreas Mavrogenis",
"Thomas Papadimos",
"Theodosios Saranteas",
"Maria Riga",
"Konstantina Panagouli",
"Andreas Mavrogenis",
"Thomas Papadimos"
],
"abstract": "Backround/Objectives We investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients.\n\nMethods We conducted a randomized study of two methods of perineural catheter advancement in a sciatic nerve block Blue Phantom simulator. Two groups of twenty catheters each (method A and method B) were evaluated under real-time ultrasound imaging. The needle in-plane/nerve in-short-axis technique was applied. In method A the catheter was advanced beyond the needle tip with the integral stylet extending along its entire length; in method B the catheter was advanced after its integral stylet was retracted by 6 cm, thus providing flexibility to the catheter’s distal end. Additionally, to assess the procedural effectiveness of method B coiling technique, a pilot study was conducted examining 25 perineural catheters coiled underneath the sciatic nerve in trauma-orthopaedic patients to document any displacement of catheters’ tip from their initial position (for 36 hours postoperatively).\n\nResults In the simulation study, method B led to a significantly higher percentage (18/20:90%) of coiled catheters than method A (3/20:15%). Two coiled catheters of method B were found kinked/obstructed. In our patients, after catheter insertion, the distal end of 2/25 (8%) coiled catheters was obstructed. One perineural catheter was dislodged. For the remaining 22 (88%) catheters, ultrasound imaging demonstrated that local anaesthetic infusion made contact with the sciatic nerve, indicating no displacement of the catheter’s distal end postoperatively.\n\nConclusion Regular straight perineural catheters can be easily coiled if their integral stylet is partially retracted. This coiling method offers extra catheter length adjacent to the nerve structure which potentially mitigates catheter tip displacement.\n\nTrial registration\nclinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview",
"keywords": [
"perineural catheter coiling",
"sciatic nerve block",
"ultrasound",
"catheter tip dislocation",
"simulation."
],
"content": "Trial registration\n\nclinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview\n\n\nIntroduction\n\nSelf-coiling catheters and catheters with a flexible, distal end-portion and wire-reinforced body can be looped, providing additional catheter length adjacent to the targeted nerves. Coiling potentially lowers dislocation rates of continuous peripheral nerve block (CPNB) catheters.1,2\n\nRegular straight perineural catheters inserted with the needle in-plane/nerve in-short-axis technique, tend to bypass the nerve due to the perpendicular orientation of the needle/catheter relative to the nerve.3,4 As of this time, there are no investigations examining whether regular straight perineural catheters (inserted with the needle in-plane/nerve in-short-axis technique) can be looped adjacent to nerves, and consequently, mitigate CPNB failure secondary to displacement.\n\nTherefore, we investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients.\n\n\nMethods\n\nTwo independent studies were conducted: 1) A simulation-based protocol in a Blue Phantom US simulator of sciatic nerve block. 2) A pilot study in 25 patients undergoing sciatic CPNB. All procedures were performed under US real-time visualization (5-9 MHz linear transducer; LOGIQ e; GE Healthcare, USA).\n\nTwo methods of perineural catheter advancement using the Blue Phantom simulator were evaluated. A 20G echogenic straight perineural catheter (SonoLong Sono, PAJUNK, Germany) with a stainless-steel helical coil-reinforced body and a steel integral stylet was used.\n\nMethod A: The catheter was advanced beyond the needle tip (under real-time US imaging) with its integral stylet extending along the entire length of the catheter (Figure 1A).\n\nInset: perineural catheter container. SC.N=Sciatic Nerve.\n\nMethod B: The catheter was advanced beyond the needle tip after the catheter’s integral stylet was retracted by 6 cm so that the catheter’s distal portion provided a more flexible end (Figure 1B).\n\nRandomization was done using a randomization generator (www.randomization.com) by means of sequentially numbered sealed opaque envelopes, including information about the sequence of method allocation.\n\nThe simulator was provided with a sciatic nerve insert (upper third of the posterior thigh) containing one nerve structure (CAE training Blue Phantom). The sciatic nerve-simulator surface distance featured different location depths (2-4 cm) (Figure 1C).\n\nA Tuohy needle (18G × 7.5 mm, PAJUNK, Germany) was inserted at the simulator’s posterior thigh (TS) from a lateral to medial direction (needle in-plane/nerve in-short-axis technique). The needle insertion angles (coronal plane) were always kept at 40 degrees (Figure 1D). In both methods, the needle was aimed behind the sciatic nerve with the curved end facing the nerve (Figure 1E). The perineural catheter was threaded through the Tuohy needle until its tip reached the needle orifice. The catheter was slowly advanced exactly 6 cm (under real-time US guidance) beyond the curved tip of the Tuohy needle, until the catheter’s distal end-portion coiled exactly under the sciatic nerve (Figure 2A). To better visualize a catheter’s trajectory, a slight heel-toe maneuver was implemented to bring the US beam perpendicular to catheter’s distal portion. Procedural time was limited to 15 seconds (total allowed performance time for each coiling maneuver). Each attempt was stored digitally and analyzed off-line (frame by frame) by two co-investigators (EP, MR) who were blinded to group allocation. The two investigators decided independently whether the catheter coiled or not. The result was considered positive (coiled catheter) only after unanimous agreement between the two investigators. If the catheter distal end did not coil or if the catheter bypassed the nerve and then coiled, the catheter was withdrawn, the needle tip reoriented (rotation of needle shaft/tip at 90 degrees), and the catheter was readvanced. In total, three attempts were allowed (overall maximum procedural time: 45 seconds). The number of attempts to coil a catheter, as well as the proportion of cases where a catheter was successfully looped on first attempt, were measured. The patency of coiled catheters was tested after normal saline (3 ml) infusion through the catheter. Contact of saline spread with the nerve was also recorded (Figure 2B). All images were taken under the same imaging settings (gain: 90 db, focus position at the level of the nerve, standard time gain compensation).\n\nC=Perineural Catheter, SC.N=Sciatic Nerve, *=LA spread.\n\nSample size calculation was based on a previous pilot simulation study including 10 CPNBs for each method, using a Blue Phantom nerve block simulator that contained two nerve structures with dimensions of 17cm × 13cm × 6cm (L × H × W), (CAE-Healthcare). Catheters were coiled (after maximum of three attempts) in 3/10 (30%) and in 8/10 (80%) cases, with method A and B respectively. Using an α error of 0.025 and a power of (1− β) at 80% to detect a 50% difference between the two methods, a sample size of 18 CPNBs in each group was required. To allow for increased data variability, 40 CPNBs were performed in a sciatic nerve block simulator. Proportions were compared using Fisher’s exact test; p values <0.05 were considered statistically significant. Interobserver agreement was assessed by using the inter-rater agreement statistic Kappa (MedCalc Software, Mariakerke, Belgium).\n\nTo assess procedural effectiveness of the preferred coiling technique (method B), a pilot study was performed. The pilot study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the “Attikon” Hospital Ethics Committee (Approval No 342, Approval Date 09/05/2024). Informed written consent was always obtained from the patients or their surrogates.\n\nStraight perineural catheters with coiled distal ends behind the sciatic nerve were examined in 25 patients (age: 28-55 years; male/female: 14/11; BMI: 26 (19-31) kg/m2) who had sustained tibia fractures (recruitment period: 10/05/2024-15/07/2024). Exclusion criteria: patients with infection in the subgluteal region, allergies to local anaesthetics, patients’ refusal to consent for the nerve block, neurological disorders, pregnancy.\n\nPatients were placed in the lateral position (with the injured leg uppermost) and a US-guided sciatic nerve block was performed under aseptic conditions (TS, EP). The sciatic nerve was visualized at the upper third of the posterior thigh (short axis view) and a Tuohy needle (21 G × 10 mm, SonoLong/NanoLine, PAJUNK, Germany) was inserted in a lateral to medial direction. The needle was placed underneath the sciatic nerve and 10 ml of ropivacaine (0.1%) were injected. A perineural catheter (with retracted integral stylet by 6 cm) (SonoLong Sono, PAJUNK, Germany) was then threaded through the needle tip and coiled behind the sciatic nerve. Confirmation of correct catheter tip placement was defined as adequate spread and contact of ropivacaine injectate (3 ml, 0.1%) with the sciatic nerve (Figure 2C). If the distribution of the local anaesthetic (LA) could not be visualized on the first infusion, 2 additional injections were performed until the distribution was clearly seen. If LA spread could not be visually confirmed, or if, when confirmed, LA did not come in contact with the sciatic nerve, the case was excluded.\n\nSubcutaneous tunneling (4 cm long) and placement of a transparent adhesive dressing were used to secure the catheter. All sciatic nerve blocks were followed by an adductor canal block (10 ml of ropivacaine 0.5%) and general anaesthesia. A continuous infusion 8-12 ml of ropivacaine 0,1% (ROPIVACAINE/KABI INJ.SOL 2 mg/ml, 28823.01.08, Fresenius Kabi Hellas A.E.) was commenced and an oral combination of paracetamol 325 mg with oxycodone 5 mg (DEPALGOS F.C. TAB 325+5 mg, 91337.01.01, MOLTENI SPA, Italy) was provided on an as-needed basis after surgery.\n\nAll CPNBs were assessed and data were collected in the post-anaesthetic care unit, and every 12 hours thereafter until 36 hours postoperatively from members of the acute pain service (APS) team not participating in the study. Observation of fluid under the dressing indicated catheter’s leakage. Unplanned external displacement and dislodgement of the catheter were defined: less than and equal to 6 cm (displacement) and more than 6 cm (dislodgement) movement of the catheter from the initial recorded depth at the point of insertion or from the distal end of the subcutaneous tunnel. The final catheter tip position was evaluated (under US imaging) 36 hours postoperatively and was identified by injecting 3 ml of ropivacaine (0.1%) through the catheter (Figure 2D). If LA spread was not confirmed after 3 injections or if, when confirmed, it did not come in contact with the sciatic nerve, the catheter’s tip was considered dislocated.\n\n\nResults\n\nIn the simulation study, overall 21 catheters coiled behind the sciatic nerve in both groups. None of the catheters coiled after bypassing the nerve. Removal of integral stylet (group B) led to a higher percentage (18/20:90%) of coiling catheters than in group A (3/20:15%), p=0.0003 (Figure 3). Of group A (n=3) and group B (n=18) coiled catheters, 3/3 (100%) and 15/18 (83%) (p=0.9) coiled on first attempt, respectively. There was significant agreement (kappa=0.9) between the two investigators assessing perineural catheter coiling. In 2 out of 18 coiled catheters (group B), saline injection was not feasible due to catheter’s distal end kinking/obstruction. Saline injections contacted the nerve in 3/3 (100%) (group A) and in 13/16 (81%) (group B) coiled catheters, respectively. After gradual uncoiling of the 2 obstructed catheters by 1 and 2 cm respectively, successful injection of saline became possible and made contact with the nerve.5\n\n* denotes p=0.0003 (method A vs method B).\n\nIn sciatic nerve CPNBs in patients with tibia fractures, the distal end of 2/25 (8%) coiled catheters was kinked/obstructed after catheter insertion, but after uncoiling the catheters by 3 cm and 2 cm, ropivacaine administration was successful. One catheter was dislodged postoperatively. Of the 22 indwelling catheters evaluated 36 hours postoperatively, the LA spread was visualized in all US examinations. Although 5/22 (22%) catheters were found externally displaced (displacement length: 2 (2-3) cm) postoperatively, no catheter tips were found dislocated. No leakage around the catheters was noticed. Neither catheter knotting nor nerve trapping/injury were recorded. Oxycodone consumprion was 12.5 (0-20) mg and the average numeric rating scale (NRS) score: 2 (0-5).6\n\n\nDiscussion\n\nAssessment of a new technique ideally should take place in humans. However, the methodology to sufficiently evaluate needles and perineural catheters on patients presents difficulties and/or ethical concerns.7–11 Therefore, we decided to initially assess this specific perineural catheter method in a “human-tissue mimicking” simulation model.\n\nThe Blue Phantom simulator was selected because its physical properties are close to human tissue and also has been employed as a testing method in peripheral nerve block needle visibility research endavours.12–17 Additionally, the Blue Phantom sciatic nerve block simulator exhibits an anatomic configuration approximating that of human anatomy.\n\nFurthermore, by partially withdrawing the integral stylet, the catheter body remained resistant to bending, while the catheter’s distal end developed a balance of malleability and strength that was required to achieve an ease of coiling, as well as lower probability for inadvertent penetration and nerve injury. We also used a Tuohy needle because its curved tip facilitated a trajectory (directional curvature) of the catheter that allowed proper target placement.\n\nIn our simulation study, the needle-insertion angles were maintained constant to attain standard angulations between the catheter’s tip and the surrounding Blue Phantom material once the catheter was threaded out of the Tuohy needle. We did not use shallow 0 to 30 degrees catheter insertion angles to optimize echogenicity because the Blue Phantom’s material is homogenous with low background echogenicity and enhances needle (and consequently perineural catheter) visibility, especially at low needle insertion angles.7 We decided, thus, to implement a steeper insertion angle of 40 degrees to simulate more difficult clinical conditions. Nevertheless, in all cases, the operator could easily advance the catheter and the two independent investigators could visually assess the trajectory of the catheters with precision and significant interobserver agreement.\n\nIn our patients, US examination of the perineural catheters (36 hours postoperatively) did not reveal any catheter tip dislocation (internally migrated catheter tip) from their initial position placement (underneath the sciatic nerve); even though 22% (5/22) of them exhibited external displacement at the point of insertion or from the distal end of the subcutaneous tunnel. It has been previously reported that regular straight perineural catheters with integral stylet display a lower tip dislocation rate when placed with the needle out-of-plane/nerve in-short axis approach.4,18 However, we can advocate that this type of perineural catheter could alternatively be inserted with good results, i.e. low dislocation rates of catheter’s tip, if the needle in-plane/nerve in-short axis approach is combined with the coiling CPNB technique.\n\nLeakage of perineural catheters is a shortcoming of the catheter-through-needle method.19 In our case series, no perineural leakage was recorded. It could be considered that a 6 cm coiled catheter path in perineural tissues may be long and winding enough to prevent local anesthetic from flowing back through the needle-puncture track. However, further investigation is imperative to support this hypothesis.\n\nA procedural weakness is the kinking of the distal end of the coiled catheters. Nevertheless, by partially uncoiling the catheter, points of obstruction can be relieved. We based our 6 cm stylet retraction on a previous report which although using a different perineural catheter brand, had a fixed 6 cm flexible/soft distal end as well.2 Although an advantage of this technique is that the stylet can be retracted from the catheter’s tip at different lengths, we did not study various lengths of stylet withdrawal (and consequently the optimal length affecting a catheter’s flexible end) that could facilitate the coiling maneuver without obstruction of the catheter.\n\nMoreover, attention should be paid to if extrapolating these observations to other ultrasound approaches, perineural catheter placement methods, as well as to diverse time-intervals of LA infusions.\n\n\nConclusion\n\nA regular straight perineural catheter can be easily coiled if its integral stylet is partially retracted. This coiling method secures a safe and adequate extra length that delivers to the operator a margin of comfort regarding the mitigation of perineural catheter tip dislocation. Further studies are required to evaluate the clinical effectiveness of this perineural catheter coiling method over other catheters’ designs and techniques.\n\nThe pilot study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the “Attikon” Hospital Ethics Committee (Approval No 342, Approval Date 09/05/2024). In accordance with the “Attikon” Hospital Ethics Committee requirements, informed written consent was always obtained from the patients or their surrogates.\n\n\nAuthor contributions\n\nTS: conception and implementation of the technique, writing, and correcting the manuscript. EP: equal contribution to the first author at all stages of the study. MR and KP: data collection and analysis. AM: recruiment and follow-up of patients. TP: commenting on all stages of the study and drafting the manuscript. All authors read and approved this final version of the manuscript.",
"appendix": "Data availability statement\n\n\n\n1. Figshare. Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator_Data.xlsx. https://doi.org/10.6084/m9.figshare.26491585.v1 5\n\nThis project contains the following underlying data:\n\n• Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator_Data.xlsx\n\n(Data from 40 catheter coiling attempts in a sciatic nerve block simulator randomized for the two coiling methods described above: method A and method B.)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n2. Figshare. Pilot study: Coiling of Echogenic Sciatic Nerve Perineural Catheters with Integral Stylet. https://doi.org/10.6084/m9.figshare.26854939.v1 6\n\nThis project contains the following underlying data:\n\n• Pilot study-original protocol.docx\n\n• Pilot study data.xlsx (data from 25 orthopaedic-trauma patients who had sustained tibia fractures and underwent a sciatic CPNB)\n\n• flow chart diagram.jpg\n\n• CONSORT Checklist.docx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nThe pilot study conducted adheres to the CONSORT reporting guidelines. A copy of the original protocol, a completed CONSORT checklist, the pilot study’s data, as well as a flow diagram are available online through Figshare. https://doi.org/10.6084/m9.figshare.26854939.v1 6\n\n\nReferences\n\nLuyet C, Meyer C, Herrmann G, et al.: Placement of coiled catheters into the paravertebral space. Anaesthesia. 2012; 67: 250–255. PubMed Abstract | Publisher Full Text\n\nSaranteas T, Poulogiannopoulou E, Ntalamagka G, et al.: Perineural coiled echogenic catheters with a flexible distal end: A brief technical report. Anaesth. Crit. Care Pain Med. 2023; 43: 101341. PubMed Abstract | Publisher Full Text\n\nSteffel L, Howard SK, Borg L, et al.: Randomized comparison of popliteal-sciatic perineural catheter tip migration and dislocation in a cadaver model using two catheter designs. Korean J. Anesthesiol. 2017; 70(1): 72–76. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIlfeld BM, Fredrickson MJ, Mariano ER: Ultrasound-Guided Perineural Catheter Insertion: Three Approaches but Few Illuminating Data. Reg. Anesth. Pain Med. 2010; 35(2): 123–126. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaranteas T, Poulogiannopoulou E, Riga M, et al.: Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator_Data.xlsx [Dataset]. Figshare. 2024. Publisher Full Text\n\nSaranteas T, Poulogiannopoulou E, Riga M, et al.: Pilot study: Coiling of Echogenic Sciatic Nerve Perineural Catheters with Integral Stylet. [Dataset]. Figshare. 2024. Publisher Full Text\n\nHocking G, Hebard S, Mitchell CH: A review of the benefits and pitfalls of phantoms in ultrasound-guided regional anesthesia. Reg. Anesth. Pain Med. 2011; 36(2): 162–170. PubMed Abstract | Publisher Full Text\n\nHocking G, Mitchell CH: Optimizing the safety and practice of ultrasound-guided regional anesthesia: the role of echogenic technology. Curr. Opin. Anaesthesiol. 2012; 25(5): 603–609. PubMed Abstract | Publisher Full Text\n\nSmith HM, Kopp SL, Jacob AK, et al.: Designing and implementing a comprehensive learner-centered regional anesthesia curriculum. Reg. Anesth. Pain Med. 2009; 34(2): 88–94. PubMed Abstract | Publisher Full Text\n\nXu D, Abbas S, Chan VW: Ultrasound phantom or hands-on practice. Reg. Anesth. Pain Med. 2005; 30(6): 593–594. Publisher Full Text\n\nEdgcombe H, Hocking G: Sonographic identification of needle tip by specialists and novices: a blinded comparison of 5 regional block needles in fresh human cadavers. Reg. Anesth. Pain Med. 2010; 35(2): 207–211. PubMed Abstract | Publisher Full Text\n\nPhelan MP, Emerman C, Peacock WF, et al.: Do echo-enhanced needles improve time to cannulate in a model of short-axis ultrasound-guided vascular access for a group of mostly inexperienced ultrasound users? Int. J. Emerg. Med. 2009; 2: 167–170. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDeam RK, Kluger R, Barrington MJ, et al.: Investigation of a new echogenic needle for use with ultrasound peripheral nerve blocks. Anaesth. Intensive Care. 2007; 35(4): 582–586. PubMed Abstract | Publisher Full Text\n\nBradley MJ: An in-vitro study to understand successful free-hand ultrasound guided intervention. Clin. Radiol. 2001; 56(6): 495–498. PubMed Abstract | Publisher Full Text\n\nMaecken T, Zenz M, Grau T: Ultrasound characteristics of needles for regional anesthesia. Reg. Anesth. Pain Med. 2007; 32(5): 440–447. Publisher Full Text\n\nSchafhalter-Zoppoth I, McCulloch CE, et al.: Ultrasound visibility of needles used for regional nerve block: an in vitro study. Reg. Anesth. Pain Med. 2004; 29(5): 480–488. Publisher Full Text\n\nHauritz RW, Pedersen EM, Linde FS, et al.: Displacement of popliteal sciatic nerve catheters after major foot and ankle surgery: a randomized controlled double-blinded magnetic resonance imaging study. Br. J. Anaesth. 2016; 117(2): 220–227. PubMed Abstract | Publisher Full Text\n\nFredrickson MJ, Leightley P, Wong A, et al.: An analysis of 1505 consecutive patients receiving continuous interscalene analgesia at home: a multicentre prospective safety study. Anaesthesia. 2016; 71(4): 373–379. PubMed Abstract | Publisher Full Text\n\nCapdevila X, Pirat P, Bringuier S, et al.: Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: a multicenter prospective analysis of the quality of postoperative analgesia and complications in 1,416 patients. Anesthesiology. 2005; 103: 1035–1045. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "327786",
"date": "06 Nov 2024",
"name": "Agathi Karakosta",
"expertise": [
"Reviewer Expertise Risk factor analysis",
"intraoperative haemodynamics",
"obstetric anaesthesia"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nCOMMENTS TO THE AUTHORS\nFirst, I would like to congratulate the authors for the interesting and relevant work. Data is presented in a detailed and coherent manner.\nHowever, there are minor issues that need clarification. 1) A flow chart for both the simulation and the pilot study would be helpful (depicting number of attempts, excluded cases or any other relevant detail).\n2) What statistical test did you employ for examining normal distribution of continuous variables. Please include this information in the “statistical analysis” section. Moreover, the way results are presented (i.e., mean(SD) or median(IQR) for continuous data and absolute/relative frequencies for categorical data or any other way ) should be mentioned in “statistical analysis”.\n3) In results you state “oxycodone consumption was 12.5 (0-20) mg …”. Are you referring to mean and range or median and IQR (interquartile range)? Please specify.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12883",
"date": "02 Dec 2024",
"name": "Eleni Poulogiannopoulou",
"role": "Author Response",
"response": "Thank you very much, indeed, for all your significant remarks. In the revised manuscript, all recommendations were considered and incorporated in the new text. Corrections in the text are highlighted with bold to facilitate perusal. 1) A flow chart for both the simulation and the pilot study would be helpful (depicting number of attempts, excluded cases or any other relevant detail). A flow chart is included in Figshare. Pilot study: Coiling of Echogenic Sciatic Nerve Perineural Catheters with Integral Stylet. https://doi.org/10.6084/m9.figshare.26854939.v1 2) What statistical test did you employ for examining normal distribution of continuous variables. Please include this information in the “statistical analysis” section. Moreover, the way results are presented (i.e., mean(SD) or median(IQR) for continuous data and absolute/relative frequencies for categorical data or any other way ) should be mentioned in “statistical analysis”. Normality was assessed by D'Agostino-Pearson test and the continuous data were described as mean (range) (Statistical analysis section). 3) In results you state “oxycodone consumption was 12.5 (0-20) mg …”. Are you referring to mean and range or median and IQR (interquartile range)? Please specify. Oxycodone consumption is presented as mean (range: highest value-lowest value)."
}
]
},
{
"id": "342696",
"date": "25 Nov 2024",
"name": "Konstantinos Kalimeris",
"expertise": [
"Reviewer Expertise Anesthesiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper presents an interesting method to coil perineural catheters which are not self-coiling. The authors conducted a study in Blue Phantom comparing if removing the stylet from the catheter before threading the catheter improves the coiling and then used this technique in 25 patients. They found that removing the stylet before threading the catheter improves coiling and they propose a solution for the obstruction of the catheter.\n\n- The purpose of the study is not clearly stated. Is it to test a technique to coil a straight stiff catheter?\n\n- Introduction should better explain the background, which research question this study aims to answer and why is it interesting to know. For example: refer 1. This reference should be added.\nWhat is the benefit from not using self-coiling catheters? Nickl et al report obstruction at 1.3%. Is there a clear cost difference?\n- Methods:\nAuthors should state if the coiling of the catheter is reliably recognized by ultrasound in all patients and Phantom. Some better quality images could help the average reader to understand the technique.\nAn important question that needs to be answered and stated in the paper is if this technique is according to the manufacturer's instructions or off-label. Does the technique involve retracting the catheter while inside the needle? Would a shear or damage of the catheter be possible by the additional manipulations?\n\n- The technique should be more clearly described. Was the coiled catheter placed inside the paraneurium? Would coiling inside the paraneurium possibly cause problems when removing the catheter? (knotting?)\nPlease state where/how many the openings of the catheter are.\nThe 15sec time limit is confusing. Please explain more the meaning of the measurement or remove\nWhat do Authors mean that \"the case was excluded\" when the anesthetic didnt reach the nerve? Please state more clearly in how many cases the technique was not feasible, as the paper regards feasibility of a new technique.\nThe study is powered for comparing two methods in the Phantom with great difference, but not for dislocation or other endpoints in the patients. There is no control group. Results are interesting, but conclusions must be carefully drawn, especially regarding complications. A section with the above limitations of the study should be included in the Discussion section.\nResults/Discussion:\n\nFigure 3 is unnecessary. Since the paper is a presentation of a technique, ultrasound images of the catheter threading and images where the coiling is clearly seen would be more helpful.\nIt would add if authors included a short literature-based comparison to other techniques of prolonged regional anesthesia.\nFrom conclusion and abstract please remove \"easily\". Authors report 12% not possible placement and 8% obstruction. A comment on the safety of the technique should be added.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Partly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12884",
"date": "02 Dec 2024",
"name": "Eleni Poulogiannopoulou",
"role": "Author Response",
"response": "We would like to thank you for the feedback and comments. In the revised manuscript, all recommendations were considered and incorporated in the new text. Corrections in the text are highlighted with bold to facilitate perusal. 1) The purpose of the study is not clearly stated. Is it to test a technique to coil a straight stiff catheter? The catheter used in the present study was not stiff; it was not made of potentially rigid material (such as plastic) but the material of the applied perineural catheters was polyurethane based: This detail is added in the introduction section (paragraph 3: purpose of the study) and in the methods section as well (paragraph 2; page 4; line 3-5). Additionally, the second paragraph of the introduction section is redrafted, further elaborating on the purpose of the study. The reference of Nickl R et all is now cited in the reference list. 2) What is the benefit from not using self-coiling catheters? Nickl et al report obstruction at 1.3%. Is there a clear cost difference? A procedural flaw may be the kinking of the distal end of the coiled catheters. Although this is a major shortcoming of the technique, by partially uncoiling the catheters, points of obstruction were relieved (Discussion section; page 10; paragraph 4). 3) Authors should state if the coiling of the catheter is reliably recognized by ultrasound in all patients and Phantom. Some better-quality images could help the average reader to understand the technique. The coiling maneuver was clearly recognized both in the blue phantom material and the case series by the investigators. The coiling maneuver of the catheter was recognizable due to its dynamic coiling motion during advancement (frame by frame analysis of the catheter in the stored video loops). In fact, the interobserver agreement of coiling maneuver between investigators was significant (k index=90) (Figure 3A). A video clearly presenting the motion of the catheter and its coiling maneuver during advancement was added (data availability section). 4) An important question that needs to be answered and stated in the paper is if this technique is according to the manufacturer’s instructions or off-label. Does the technique involve retracting the catheter while inside the needle? Would a shear or damage of the catheter be possible by the additional manipulations? This technique did not follow the manufacturer’s instructions but is an off-label technique. In fact, the methodology to sufficiently evaluate needles and perineural catheters on patients (not following manufacturer’s instructions) presents difficulties and/or ethical concerns. Therefore, we set out to initially assess this specific perineural catheter method in a “human-tissue mimicking” simulation model (Discussion section; page 9; paragraph 2). In fact, if the catheter was not coiled with the first attempt, it was then gently retracted and re-advanced; nevertheless, neither shear nor obvious damage nor knotting of the catheter were noticed (Results section; page 8; paragraph 3). 5) The technique should be more clearly described. Was the coiled catheter placed inside the paraneurium? Would coiling inside the paraneurium possibly cause problems when removing the catheter? (knotting?) The technique is more clearly described by incorporating in the text more details regarding the catheter placement in the paraneurium (Methods section; page 7; paragraph 2, 3 and 4) Knotting was not noticed in both studies. 6) Please state where/how many the openings of the catheter are? The catheter had one opening on its tip (Methods section; page 4) 7) The study is powered for comparing two methods in the Phantom with great difference, but not for dislocation or other end points in the patients. There is not a control group. A section with the above limitation should be included. Indeed, our clinical study was not powered, nor did it include a control group. This is an obvious methodology weakness, even though the intention was to deploy a pilot study supplementary to the simulation study, in addition to providing definitive preliminary data for a future randomize control clinical trial. We concur with the reviewer’s comment and a new paragraph in the limitation section was added. 8) Figure 3 is unnecessary. Since the paper is a presentation of a technique, ultrasound images of the catheter threading and images where the coiling is clearly seen would be more helpful. Figure 3 is omitted, and an explanatory video is included (data availability section). 9) From conclusion and abstract please remove \"easily\". Authors report 12% not possible placement and 8% obstruction. A comment on the safety of the technique should be added Both in the conclusion and abstract section the word \"easily\" was removed. 10) It would add if authors included a short literature-based comparison to other techniques of prolonged regional anesthesia. A new reference was added Nickl R et all in the reference list, emphasising the use of other types of coiled catheters in CPNB applications. In order to comply with the word limit (2500), we decided upon minimising the above comparison. Our article is a technical brief report focusing on specific technical details. 11) The 15sec time limit is confusing. Please explain more the meaning of the measurement or remove The 15 sec limit was an arbitrary decision, because we aimed to proceed with the simulation in a time limiting manner. In fact, the reviewer correctly considers that the certain time limit potentially confuses the implementation of the technique, but for the reason of group comparisons (coiling ability) a limited time period of implementation was imperative."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1103
|
https://f1000research.com/articles/13-1458/v1
|
02 Dec 24
|
{
"type": "Study Protocol",
"title": "Impact of haptic simulator in prosthodontics training during preclinic dental education: a systematic review protocol",
"authors": [
"Oumaima Tayari",
"Cyrine Sahli",
"Jamila Jaouadi",
"Cyrine Sahli",
"Jamila Jaouadi"
],
"abstract": "Background Prosthodontics significantly impacts oral health-related quality of life, especially oral comfort, functions, aesthetics, and overall well-being. This discipline is grounded in a solid academic and evidence-based understanding of fundamental principles for managing dental diseases and aims to restore the health of teeth and supporting tissues and compensate missing ones. Dental education is evolving quickly with the rise of digital dentistry, especially in prosthodontics. Integrating augmented reality simulations and haptic feedback has significantly advanced this transformation. This systematic review protocol intends to determine the effectiveness of haptic simulators in prosthodontics training during preclinical dental education.\n\nMethods An exhaustive search strategy will be employed, exploring PubMed, Scopus, EBSCO, Web of Science and Cochrane Central to select relevant studies, thereby enhancing the robustness of the review findings. Boolean operators (AND,OR) were utilized to assemble MeSH terms and relevant keywords. Titles and abstracts screening to identify studies that satisfy the eligibility criteria was followed by the quality and risk of bias assessment for the selected studies, via the Cochrane Collaboration’s tool and the Newcastle-Ottawa Scale (NOS). Data will be collected via standard form. Reviewers disagreement will be solved throughout debate, or by referring to a third opinion. This protocol will adhere the recommendations appointed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).\n\nDiscussion The outcomes of this systematic review are highly significant for dental education exploring the importance of enhancing haptic simulation during preclinic prosthetic training. Recognizing the strengths and weaknesses of virtual reality (VR) in relation to traditional preclinical training methods is crucial for developing effective educational strategies. This understanding can lead to enhanced training outcomes and increased student satisfaction, which in turn contributes to improved quality of clinical prosthetic services.\n\nSystematic review registration PROSPERO: CRD42024603681 (Registered on 30/10/2024).",
"keywords": [
"Haptic technology",
"simulation training",
"augmented reality",
"virtual reality",
"dental education"
],
"content": "Introduction\n\nImprovements in digital prosthodontics have profoundly transformed the field of dentistry.1 As a result, dental education models have evolved to keep pace with these changes. Recent technological innovations present exciting opportunities to enhance student education, making learning more interactive and effective. By integrating these advancements into the curriculum, educators can better prepare students for the evolving demands of clinical practice, eventually conducting to enhanced patient care and results.\n\nDental educators can leverage digital advancements to enrich the educational experience, particularly by incorporating haptic technology into dental school curricula. This integration allows for hands-on, simulated practice that closely mirrors real clinical scenarios, helping students develop essential skills in a controlled environment. By embracing these technologies, educators can foster a deeper understanding of complex procedures, improve student engagement, and ultimately prepare future dental professionals to meet the challenges of contemporary practice.\n\nTraditionally, first-year dental students initiate honing their manual ability with typodonts. They move from desktop typodonts to mannequin heads that imitate a clinical context.1 Typodonts are designed to mimic dental arches, and when placed in mannequin heads, they aid in instructing students on appropriate clinical posture and ergonomic practices. Typodonts have been used in dental training for a long time, but the advancement of virtual and augmented reality (VR/AR) technologies has broadened their applications in the medical and dental fields. VR/AR engineering procedures are typically head-mounted appliances with screens and haptic controllers that allow users to react with virtual mock-ups and varieties of softwars.2 Both technologies can also incorporate haptic feedback, which allows users to feel simulated sensations such as touch and pressure.\n\nWith the advent of technologies like mixed reality (MR) haptic-based dental simulators, students can enhance their motor skills while receiving immediate feedback, all without the need for an instructor’s physical presence.3–5\n\nThis technology can be applied across all specialties in dentistry such as implant placement, crown and bridge preparation, a wide range of procedures with varying levels of difficulty.5 It has been proposed that combining this technology with conventional preclinical training methods can strengthen students’ skills and confidence prior to their clinical experiences.\n\nThis systematic review protocol targets to investigate the aptitude of haptic simulators in enhancing prosthetic training of pre-graduated dental students. An initial search of MEDLINE, the Cochrane Database of Systematic Reviews, and the JBI Database of Systematic Reviews was carried out, and as far as we are aware, there are no available systematic reviews addressing the raised issue.\n\n\nProtocol\n\nThis protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations to ensure a complete and clear approach.6\n\nThe approach complies with the norms established by the F1000 journal. Additionally, this protocol has been reported with PROSPERO, the international prospective register for systematic reviews (CRD42024603681) since 30/10/2024.\n\nThe main objective of the review is to evaluate the efficiency of haptic simulators in comparison to standard educational methods on skill acquisition, retention, and overall learning outcomes for dental students for prosthetic preclinic training. The secondary objectives are to measure knowledge retention and to compare error rates.\n\nThe inclusion criteria are outlined by specifying the crucial parts of the research question according to the PICO plan7:\n\nType of population: Dental students in preclinical prosthodontic training.\n\nIntervention type: The use of Virtual reality haptic simulator in preclinical prosthodontic training. The training covers a variety of tasks performed in the course of treatment with one of the different types of dental prostheses.\n\nComparison group: Conventional typodont training.\n\nTypes of outcomes: Improvements in student learning and skill development.\n\nMeasures of effect: This study will evaluate results based on quantitative and qualitative measurements.\n\nStudy Types: randomized controlled trials (RCTs) that randomly assign participants to either the haptic simulator group or the standard training group to evaluate differences in outcomes, non-randomized controlled trials (non-RCTs), observational studies, including cohort and case-control studies that follow groups of students trained with haptic simulators and those using traditional methods over time to compare their performance and skill retention, will be included if they meet a minimum of 15 criteria from the STROBE quality exigences.8–10\n\nCase reports and letters to the editor will be excluded because of their restricted reproducibility. Furthermore, non-English papers will be eliminated to minimize language bias and address source limitations. Studies with insufficient data or low methodological quality will be dismissed to ensure the accuracy and validity of the review.\n\nA thorough search strategy includes relevant controlled vocabulary terms and Medical Subject Headings (MeSH) terms related to the research issue: haptic technology, dental education, dental student, prosthodontics, High Fidelity Simulation Training, virtual reality (VR), augmented reality (AR).\n\nTo reduce the risk of overlooking pertinent studies, various databases, such as MEDLINE, Web of Science, EBSCO, Scopus and Cochrane Central will be carefully consulted.\n\nTo promote inclusiveness, unprinted papers and current clinical trials through sources such as conference proceedings, dissertations, and clinical trial registries will be located.\n\nTo ensure a comprehensive review, qualified reviewer will assist in determining sources of grey literature and judging their relevance to the study.11\n\nAdditionally, bibliographies of included studies will be manually reviewed to discover further papers that may not have been captured via automatic searches.\n\nThis strategy seeks to eliminate publication bias and guarantee a comprehensive review of the available evidence.\n\nAfter performing a comprehensive search through chosen databases, identified articles will be classified via Zotero software, with duplicate papers elimination. Two reviewers (OT, CS) will separetly evaluate the titles and abstracts of identified studies. Those that meet the eligibility criteria will have a full-text review by the same reviewers. Furthermore, reviewers will meticulously check the references of selected articles to uncover further pertinent papers. Studies that satisfy the selection criteria will then advance to the data extraction phase. Justifications for excluding papers that do not meet the criteria will be mentioned in the finished assessment.\n\nReviewers’ discrepancies will be dealt by means of debate. If necessary, an experienced reviewer (JJ) will be involved to ensure accuracy, reach an agreement and uphold the validity of the selection approach.\n\nThe results from the initial identification to final selection procedure will be carefully described and presented in the eventual systematic review, respecting adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations.12,13\n\nTwo separated reviewers will conduct the evaluation and mark the studies to reduce bias and improve credibility.14 Disagreements in the evaluations will be solved through discussion or by referring to a supplementary opinion to reach an accord.\n\nTo ensure the accuracy of the results, the methodological quality and risk of bias of the included studies will be assessed through normalized tools.15\n\nFor randomized controlled trials, the Cochrane Risk of Bias (ROB II) scale will be employed to evaluate methodological rigor according to crucial elements: randomization process, conformity to planned interventions, integrity of outcome data, outcome measure, and precision in reporting results. Each element will be classified as having low, high, or unclear risk of bias.16\n\nThe Newcastle-Ottawa Scale (NOS) will serve to assess non-randomized studies basing on scoring the selection of study participants, group comparability, and outcome ascertainment. Higher scores reflect better methodological quality.17\n\nThis approach of the evaluation of methodological rigor and bias will garantee that the study’s outcomes are grounded in high-quality evidence.\n\nData items: Data pointed from the selected studies will encompass participant demographics and study characteristics. Further information about haptic simulator features, means of outcome measurement, level of education and type of prosthetic activity are to be determined.\n\nExtraction method: The same reviewers will individually gather information from all selected studies into detailed extraction template specifically developed for this task. This template has been rigorously evaluated during a pilot phase to ensure consistency and accuracy in data handling. Any discrepancies will be resolved through discussion, with another reviewer involved if necessary. Final decisions will be reached by majority agreement. This organized method ensures precise and reliable conclusions for future analysis.\n\nThe extracted information will be thoroughly examined to be utilized to justify the efficacy of haptic simulator in preclinical prosthetic training. An primary descriptive synthesis will identify the study determinants, participant characteristics, simulator features, prosthetic field (fixed, removable, supra implant) and outcome measures. Quantitative analysis will evaluate outcomes with 95% confidence intervals and control non-homogeneity crosswise studies via statistical tests.\n\n\nDiscussion\n\nThis systematic review will comprehensively assess the current literature on the utilization of haptic simulators during prosthetic education. The findings will be particularly beneficial for students and teachers, especially in preclinical training.\n\nBy evaluating the efficacy of haptic technology in hand skills improvement, this review intends to find evidence-based guidance on novice’s sensorimotor acquisition concerning prosthetic procedures and dental preparation assessment. Moreover, this review will identify activities most concerned by this tool and the prosthetic procedures most likely to be simulated by haptic technology, and propose a strategy for introducing this tool into the curriculum of dental students in order to improve the sense of touch, particularly for immersion and force feedback. By that, students can learn the appropriate amount of pressure to apply when using dental instruments.\n\nAs a result, this review will be a considerable source for justifying pedagogical approach and improving the quality of academic training and dental care subsequently provided.\n\nNo ethical approval is required for this systematic review protocol.\n\nThis systematic review is in the selection phase. This protocol has been registered with PROSPERO (CRD42024603681) since 30/10/2024.\n\nFigshare, PRISMA-P-checklist for impact of haptic simulator in prosthodontics training during preclinic dental education: a systematic review protocol, DOI: https://doi.org/10.6084/m9.figshare.27761997.v1, CC BY 4.0.18\n\nThe project contains the following dataset:\n\n• PRISMA-P-checklist.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nReferences\n\nShah KC, Kane BA, Lloren PA: The New Age of Prosthodontics Education: Digital Prosthodontics and Simulation. J. Calif. Dent. Assoc. 2021; 49(6): 401–405. Publisher Full Text\n\nDzyuba N, Jandu J, Yates J, et al.: Virtual and augmented reality in dental education: The good, the bad and the better. Eur. J. Dent. Educ. 2022 Nov 6. Epub ahead of print. PubMed Abstract | Publisher Full Text\n\nHsu MH, Liu CM, Chen CJ, et al.: Virtual 3D tooth creation for personized haptic simulation training in access cavity preparation. J. Dent. Sci. 2022; 17: 1850–1853. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLu MY, Peng CY, Chang YC: Interns’ perception of haptic virtual reality oral surgery simulator learning for impacted lower third molar extraction. J. Dent. Sci. 2022; 17: 1825–1826. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTurkyilmaz I, Marshall LS: Preclinical prosthodontic training with mixed reality haptic-based dental simulator. J. Dent. Sci. 2023 Apr; 18(2): 905–906. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoher D, Shamseer L, Clarke M, et al.: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015; 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Connor AM, et al.: Conducting systematic reviews of intervention questions I: writing the review protocol, formulating the question and searching the literature. Zoonoses Public Health. 2014; 61: 28–38. Publisher Full Text\n\nSTROBE Statement-Checklist of items that should be included in reports of cohort studies.[cited 2020 Dec 10].\n\nSTROBE Statement-Checklist of items that should be included in reports of cross-sectional studies.[cited 2020 Dec 10].\n\nChecklist for Randomized Controlled Trials Critical Appraisal tools for use in JBI Systematic Reviews.[cited 2020 Dec 10].\n\nMigliavaca CB, Stein C, Colpani V, et al.: How are systematic reviews of prevalence conducted? A methodological study. BMC Med. Res. Methodol. 2020 [cited 2020 Dec 12]; 20(1): 96. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHiggins JPT, Thomas J, Chandler J, et al.: Cochrane Handbook for systematic reviews of interventions version 6.1 (updated September 2020). London: Cochrane; 2020.\n\nHiggins JPT, Lasserson T, Chandler J, et al.: Methodological Expectations of Cochrane Intervention Reviews. London: Cochrane; February 2021. Version. MECIR Version February 2021 clean final_1.\n\nZeng X, et al.: The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J. Evid. Based Med. 2015; 8(1): 2–10. PubMed Abstract | Publisher Full Text\n\nChecklist for Randomized Controlled Trials Critical Appraisal tools for use in JBI Systematic Reviews.[cited 2020 Dec 10].\n\nSterne JAC, Savović J, Page MJ, et al.: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clinical Research ed.). 2019; l4898. Publisher Full Text\n\nWells GA, Shea B, O’Connell D, et al.: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute; Accessed January 20, 2024.\n\nTayari O: PRISMA-P-checklist for impact of haptic simulator in prosthodontics training during preclinic dental education: a systematic review protocol. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "350913",
"date": "03 Jan 2025",
"name": "Ling Ye",
"expertise": [
"Reviewer Expertise Stomatology Education"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAs technology advances, the use of digital teaching methods, such as haptic simulators, in preclinical oral skills training is growing rapidly. This systematic review aims to provide robust evidence on the effectiveness of haptic simulators in prosthodontic training during preclinical dental education, thereby assisting dental educators in refining their teaching strategies. The systematic review protocol is well-defined and largely aligns with PRISMA. Here are several suggestions for the authors' consideration:\nIn the introduction, the authors have mentioned virtual reality (VR), augmented reality (AR), and mixed reality (MR), yet the search terms did not encompass MR. I wonder the interplay between the three technologies and the rationale for excluding MR from your search. Search Strategy section: Please list all the databases you intend to consult. Data Extraction section: It's recommended to extract additional details, such as the length of intervention application. Data Analysis and Synthesis section: Does the quantitative analysis refer to meta-analysis? If so, please describe the methods for assessing heterogeneity, principles for model selection, sensitivity analysis, and other relevant analyses. It's suggested to include the method for evaluating the quality of evidence found in the systematic review.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "355244",
"date": "11 Jan 2025",
"name": "Ritik Kashwani",
"expertise": [
"Reviewer Expertise Metaverse Applications in DentistryBlockchain and Cryptocurrencies in HealthcareArtificial Intelligence (AI) in DentistryCone Beam Computed Tomography (CBCT) Platelet-Rich Fibrin (PRF)"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGrammar and Syntax: There are minor grammatical errors (e.g., “garantee” instead of “guarantee”). A final proofread is recommended.\nFigures and Flowcharts: A PRISMA flowchart showing the selection process could enhance clarity and align with guidelines.\nIncorporate Mixed Reality (MR): While VR and AR are discussed, MR is not adequately included. Clarify why MR is excluded or consider adding it to broaden the scope.\nSearch Strategy: Explicitly list all databases and search terms used. Including MR and other emerging technologies could strengthen the protocol. Clarify if hand-searching reference lists or reaching out to authors for unpublished data will be part of the strategy.\nData Extraction: Expand details to include the length of intervention application, fidelity levels of simulators, and participant feedback for a holistic analysis. Ensure consistency by using validated data extraction forms.\nData Analysis: Specify if meta-analysis is planned. If so, detail methods for: Heterogeneity assessment (e.g., I² statistic). Sensitivity analysis and publication bias testing. Criteria for fixed vs. random effects model selection. Include a framework for synthesizing qualitative findings.\nQuality of Evidence: Adopt GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) or similar methodology for assessing the quality of evidence. Discuss plans for addressing biases and limitations in included studies.\nDiscussion Section: Highlight potential implications for integrating haptic simulators into curricula, addressing cost, and training challenges. Address potential scalability for different educational institutions.\nCompare the Study with Previously Published article , Some research you can read to compare - [Ref 1] and [Ref 2].\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1458
|
https://f1000research.com/articles/13-1457/v1
|
02 Dec 24
|
{
"type": "Research Article",
"title": "A Bali perspective: Intention for sustainable customary and village forest management in the post pandemic era ",
"authors": [
"Shine Pintor Siolemba Patiro",
"Kresno Agus Hendarto",
"Dian Charity Hidayat",
"Lukas Rumboko Wibowo",
"Digby Race",
"I Wayan Widhana Susila",
"Sutrihadi Sutrihadi",
"Krisdianto Sugiyanto",
"Gerson Ndawa Njurumana",
"Hani Sitti Nuroniah",
"Dewi Ratna Kurniasari",
"V. Rachmadi Parmono",
"Atfi Indriany Putri",
"Abdurakhman Abdurakhman",
"Tri Astuti Wisudayati",
"Ramawati Ramawati",
"Yudha Satria Aji Pratama",
"Shine Pintor Siolemba Patiro",
"Lukas Rumboko Wibowo",
"Digby Race",
"I Wayan Widhana Susila",
"Sutrihadi Sutrihadi",
"Krisdianto Sugiyanto",
"Gerson Ndawa Njurumana",
"Hani Sitti Nuroniah",
"Dewi Ratna Kurniasari",
"V. Rachmadi Parmono",
"Atfi Indriany Putri",
"Abdurakhman Abdurakhman",
"Tri Astuti Wisudayati",
"Ramawati Ramawati",
"Yudha Satria Aji Pratama"
],
"abstract": "Background The COVID-19 pandemic has generated significant impacts on the forestry sector. Employment layoffs have led to an increase in return migration, resulting in additional labor supply and heightened family economic burdens. This research employs the Theory of Planned Behaviour (TPB) framework to examine and predict sustainable forest management practices among families managing customary forests and village forests in Bali.\n\nMethods Purposive sampling was used to collect data from 71 managers of customary forests and village forests in Tenganan and Wanagiri. Partial least square-structural equation modelling (PLS-SEM) was used to analyze the acquired data.\n\nResults The findings demonstrated that TPB can explain the sustainable forest management. The incorporation of an additional construct, Tri Hita Karana (THK), enhanced the model’s predictive power for both managerial intentions and behaviors in sustainable forest management. Specifically, THK influences management intentions through the mediation of attitudes, subjective norms, and perceived behavioral control.\n\nConclusions This study established that THK, a fundamental value system in Balinese society, serves an antecedent predictor of behavioral intentions toward sustainable forest management. The relationship between THK and sustainable forest management intentions is mediated by attitudes, subjective norms, and perceived behavioral control. This research makes significant theoretical and managerial contributions. First, it validates the established TPB framework within the context of COVID-19’s impact in Bali. Additionally, it provides scholars with insights for identifying other potential constructs that may influence forest land managers’ behavior.",
"keywords": [
"Theory of planned behavior”",
"COVID-19",
"“return migrants”",
"“sustainable forest management”",
"“Tri Hita Karana”"
],
"content": "Introduction\n\nAt the end of 2019, the World Health Organization (WHO) for the first time recognized a COVID-19 case in China and deemed it as a global pandemic on March 11, 2020. “Over the past two weeks, the number of cases outside China has increased 13-fold, and the number of affected countries has increased 3-fold,” said WHO Secretary-General Tedros Adhanom Ghebreyesus (Dzulfaroh 2021).\n\nTo limit the spread of COVID-19, all governments globally were taking drastic measures by locking down entire countries or most affected cities and towns and banning outsiders from entering their countries (Fotiadis et al. 2021). As a result, patterns of social, economic, and human behavior alter quickly and dramatically (Cooke et al. 2021). This behavior change has resulted in reduced greenhouse gas emissions, air pollution, noise pollution, and waste which makes beaches in different countries cleaner (Ming et al. 2020; Bao and Zhang 2020; Dantas et al. 2020; Maji et al. 2021; El-Sayed et al. 2021; Rahman et al. 2021). However, it has also resulted in weakly enforced regulations and environmental law handling (Corlett et al. 2020). Comparing the same period in 2019 to all tropical areas, deforestation increased by 63% to 136% (Brancalion et al. 2020). In Gundaki Province, Nepal, COVID-19 has suspended all types of forestry and ecotourism-based businesses, research, and monitoring activities. It has also led to a drastic increase in illegal logging and poaching both inside and outside protected areas, a drastic reduction in the income of the middle and lower classes, and an increase in rural and urban poverty (Laudari et al. 2021). Besides that, extensive protective measures such as mask and glove use have increased organic and inorganic waste in the environment (Zambrano-Monserrate et al. 2020).\n\nIn Indonesia, President Joko Widodo and Minister of Health Terawan announced the Covid 19 case at a press conference at the Presidential Palace on March 2, 2020. Two patients with Covid 19 were confirmed. Patient 1 is a 31-year-old woman while Patient 2 was a 64-year-old woman. They are a mother and daughter who live in one house in Depok, West Java. Even though at the beginning of the pandemic the Government received much criticism from the public, on May 25, 2022, at the 7th Global Platform for Disaster Risk Reduction 2022 in Bali, Indonesia was highly appreciated by the President of the UN General Assembly, Abdulla Shahid, in his remarks at the event (BNPB 2022).\n\nTourism is the backbone of the economy in Bali. When the COVID-19 pandemic hit, the impact was very significant. In the Bali Economic and Investment Forum on April 8, 2021, the Head of the Bali Tourism Office stated, “Three thousand employees were laid off and consequently increased the unemployment in Bali. While usually, it has the lowest rate nationally, it is now in 18th position” (CNN 2021). The open unemployment rate in February 2020 was 1.25%, which increased to 5.42% in February 2021 and fell slightly to 5.37% in February 2022. The poverty rate increased, in March 2020 it was 165.19 (3.78%) while in March 2021, it was 201.97 (4.53%) (BPS 2022). Like in other countries the laid-off employees generally returned to their hometowns and were involved in work.\n\nPrevious researchers (i.e., Pramana et al. 2022; Khalid et al. 2021; Zenker and Kock 2020; Higgins-Desbiolles 2020; Guridno and Guridno 2020; Baum and Hai 2020; Qiu et al. 2020; Nicola et al. 2020; Foo et al. 2021; Qiu et al. 2021; Škare et al. 2021; Abbas et al. 2021; Zhang et al. 2021; Fotiadis et al. 2021; Bae and Chang 2021) have studied the COVID-19 pandemic and the impact on tourism. Reviewing these literatures, we found that (1) most of the studies were based on assumptions (useful for scenario analysis) and generally, they used secondary data or online survey, instead of the actual data taken in the field; (2) most of these studies did not focus on migrants affected by layoffs and acceptance of the hometown of the returning migrants; and (3) families of migrant workers who have laid of were affected by both internal factor (biological, psychological, and social) and external factor (assistance from the central and local governments).\n\nThis study aims to fill that gap. First, this study focuses on the hometown of the migrants by focusing on behavior of migrant-receiving families (especially managers of customary forests land and village forests). Second, this study collects field data. Third, this study examines internal factors using the planned behavior theory (TPB) to understand behavior of migrant receiving families. Gao et al. (2017) stated that although TPB has been widely used in predicting individual pro-environmental behavior, there are 2 limitations. The limitation is that TPB is a theory of self-interest and all variables in TPB are rational predictors (Bertoldo and Castro 2016). In other words, TPB assumes that human behavior is simple, so that people make decisions using rational thinking; in fact human behavior is very complex (Ajzen 1991; Petty and Cacioppo 1986). Thus, to improve the ability of TPB in explaining and predicting intentions and pro-environmental behavior, it is necessary to consider other variables to be included in the model (Conner and Armitage 1998). This study has expanded the TPB framework by including THK (as a value) construct to measure the impact on behavior of customary forest and village forest managers.\n\nTPB is the most frequently cited theory to explain human behavior (Sussman and Gifford 2019). Numerous empirical studies have examined and validated this theory, which has been found to be an effective explanation for a range of pro-environmental behaviors (Sarkis 2017; Du and Pan 2021). This theory is a development of the theory of reasoned action and was first proposed by Icek Ajzen in 1985. This theory states that human behavior is guided by 3 kinds of considerations, namely behavioral belief, normative belief, and control belief, which in turn produce certain results such as attitudes on behavior, subjective norm (SN), and perceived behavioral control (PBC) (Yadav and Pathak 2017).\n\nValues influence behavior when they are relevant to the context and important to the individual (Schwartz 1992). Individuals hold a relatively stable set of values that are internalized from the early stages of life and change little later (Schwartz 1994). In other words, values are used to characterize cultural groups, characterize society, and characterize individuals, to explain the motivational basis of attitudes and behavior (Schwartz 2012). Schwartz’s approach is crucial for social-psychological study for various reasons. First, it directly deals with theory, and its fundamental components are included into early social scientific research (Desender et al. 2011; Ahmad et al. 2020). Second, the framework makes use of value dimensions measurements that are consistent across cultures (Burgess and Steenkamp 2006; Schwartz 2006; Ahmad et al. 2020).\n\nStern et al. (1993) proposed three value orientations that were pertinent to consumers’ environmental concerns as an early application of Schwartz’s value theory: self-interest, altruism toward other humans, and altruism toward other species and the biosphere. Later, Stern and Dietz (1994) asserted that a person’s perspective about themselves (egoistic value orientation), other people (altruistic value orientation), or plants and animals (biospheric value orientation) will determine how important they view environmental issues.\n\nThe term THK derives from the words “Tri” which means three, “Hita” which means happiness. and “Karana” which means cause. Therefore, lexically the term means three causes of happiness creation (Yhani and Supastri 2020). Some examples of the implementation of our gratitude to God are (1) with sradha (belief or trust) and bhakti (activity of getting closer to God) giving yadnya (divine service) and praying to God. Doing Punia (offerings) without any strings attached, doing tirtta yatra (holy journey) to places that can lead to their sacred values; (2) Caring for others, especially to a relative (fellow) hit by a disaster. As role model that illuminates others, at least we must be a torch for ourselves first by diligently talking of virtue while doing a real action; (3) The natural surroundings or our environment is our closest mirror of caring for nature. The environment looks beautiful, clean, and neatly arranged, which means that we can realize one of the THK. In the Bhagawadgita it is said that “Satatam kirtayatom mam. Yatantas ca drsha vrtatah. Namasyantas ca mam bhatya. Ni tyayuktah upsate” (IX.14) (Always exclusively praise Me and do the duty of service uninterruptedly. You who worship me unceasingly and with eternal devotion are close to Me) (Budiastika 2022).\n\nThus, aim of this study is to improve understanding of the behavior of migrant receivers. In other words, this study aims to answer the question of the insignificant impact of the damage on customary forests and village forests management in Bali during the COVID-19 pandemic. This study proposes 2 questions. They are (1) what internal factors significantly influence the behavior of customary/village forest managers; and (2) how these factors shape the behavior of the managers of customary forests and/or village forests.\n\nThis article illustrates the process as follows. The second section describes context, sample, measurement, and analysis of data. We present results and discussion in the third section. Finally, conclusions, limitations, and suggestions are presented in the fourth section.\n\n\nMethods\n\nThe study was conducted in two villages, namely Tenganan Village and Wanagiri Village. The two villages were chosen because (1) Tenganan Village has customary forests and Wanagiri Village has village forests; (2) each customary forest and village forest manager has joined a forest farmer group that was formed before the COVID-19 pandemic; (3) there were no extreme land cover changes during the COVID-19 pandemic (see Figure 1).\n\nNoted: Bali Island (A) (Source: BPS, 2023); Village forest land cover in Wanagiri 2018 (B1), 2020 (B2), and 2022 (B3); Customary forest land cover in Tenganan 2018 (C1), 2020 (C2), and 2022 (C3).\n\nTenganan Village is located in Manggis District, Karangasem Regency. The population is 1,044 people. The people of Tenganan Village are an early Hindu community (Bali Aga) with the Indra sect. They do not recognize castes like Balinese people in general. Based on Decree number 1546/MenLHK-PSKL/PKTH/Kum.1/2/2019, the Minister of Environment and Forestry (MoEF) designated the forest in Tenganan as a customary forest. The area of the Tenganan customary forest extends approximately 591 hectares consisted of 226 hectares of protected forests and 365 hectares of productive forests. The Tenganan customary forest is managed by all indigenous peoples, numbering around 668 people or 225 families. All residents are Hindus (BPS 2020). They are guided by customary rules (awig-awig ) in managing customary forests.\n\nWanagiri Village is situated in Sukasada District, Buleleng Regency. It has village forest that managed by a Village-Owned Enterprise named “Eka Giri Karya Utama”. With a total of 250 hectares, this village forest is divided into 2 zones of 80 hectare of protection zone and 170 hectare of utilization zone. The village forest was designated with the Decree of the Governor of Bali Number 2017/03-L/HK/2005. Most of the village forests have been planted with coffee. Total population in the village of Wanagiri is 4,056 people; 51.58% of which are men and 48.41% are women. Religion of the population are Hindus (98.91%); Islam (0.67%); Christian (0.201%); Catholic (0.17%); and Budhis (0.05%) ( Sistem_Informasi_Desa, 2023). There are 296 families involved in village forest management. This number is divided into 3 forest farmer groups, namely Wana Amerta (with 78 families); Puncak Manik (35 families); and Jagra Wana (78 families).\n\nIn order to protect the public’s health during the COVID 19 epidemic, the government imposed travel restrictions, promoted the 3M campaigns (mask use, hand washing, and keeping a distance), and gave out immunizations. In addition, the government also ensured the digitalization of health care. When a positive case of COVID-19 is suspected, medicine is immediately sent free of charge. Not all countries allow free transport of medically prescribed medicine.\n\nFrom an economic standpoint, the Government implemented a partial lockdown or locally known as Large-Scale social restriction (PSBB). This is quite rational because people can still carry out economic activities. The enforced PSBB in these areas is considered far more realistic than implementing a full lockdown throughout the country (Roziqin et al. 2021). In addition, the government also provides a social safety net. There are several social policies which include Family Hope Program, Staple Food Cards, Pre-Employment Cards, electricity subsidies, additional market and logistics operations, relief of credit payments for informal workers, and BLT Dana Desa (direct cash assistance to the village) (for more details, see Figure 2).\n\nNote: Figure 2 modified from Bista et al. (2022).\n\nOperationally, the research question of this study can be illustrated in Figure 3.\n\nNoted: Planned Behavior Theory (A). Source: Yuriev et al. (2020); Tri Hita Karana (B) Source: Adityanandana & Gerber (2019).\n\nAs seen in Figure 3(A), attitudes, SN, and PBC are the predictors of intention. Consequently, this study examines three hypotheses derived from the conceptual model:\n\nFigure 3(B) shows that THK is a harmonious integration of 3 related realms, namely the human world (pawongan), the natural world (palemahan), and the spiritual world (parahyangan). The self (microcosm) is not separate from the universe (macro cosmos) and both are composed of the same elements (Adityanandana and Gerber 2019).\n\nThe framing of THK as “culture”, “tradition”, and “local wisdom” can be criticized by using insights from various scientific domains (Roth and Sedana 2015). In this study, we frame THK as a value. Value is a belief that is closely related to influence. When values are activated, they are infused with feelings (Schwartz 2012). He also gives an example of people who consider independence an important value. People become aroused when their independence is threatened. They may feel despair when they are powerless to protect it and feel happy when they can enjoy it. Thus, the hypothesis proposed is:\n\nFinally, Figure 3(C) shows the model proposed by this study, where value (THK) is an antecedent of TPB.\n\nPurposive sampling was used in this study. According to Cooper and Schindler (2013), purposive sampling is a non-probabilistic sampling that meets specific criteria. Following of the study objectives, the specific criteria are peple who: (1) cultivators of customary forests and village forests; (2) adults; (3) have a good literacy level; (4) responsible for the laid-off immigrants due to the COVID-19 pandemic; and (5) willing to be involved in the study.\n\nThe sample size for a multivariate analysis should be 10 times more than the total number of variables to be examined, according to Roscoe in Sekaran and Bougie (2016). Depending on the complexity of the model, a sample size of 5 or 10 or 15 cases per parameter (Kline 2016). Meanwhile, the number of representative samples used in multivariate analysis was between 100 and 200, or five times as many as the questionnaire’s question items (Hair et al. 2018). Based on what has been stated and also because not all managers of customary forests and/or village forests accept migrants, we targeted a sample size of 200 respondents.\n\nIn this study, structured questionnaires were used. The questionnaire consisted of two major parts, namely: (1) inquires about THK, attitudes, SN, PBC, and intention to continue to manage forest in a sustainable manner; and 2) inquires about the respondent’s profile. The question items were modified from earlier studies by Ariyanto et al. (2017); Homer (1995); Ofoegbu and Speranza (2017); Buyinza et al. (2020); Borges and Lansink (2016). Because the question items are translated from English to Indonesian, the accuracy of the translation does matter (Jogiyato 2013). Therefore, we asked linguists at Yogyakarta State University to translate the question items from English into Indonesian. The translated Indonesian version was translated back into English by the author’s colleagues who had studied abroad, to see the possible significant differences.\n\nData in this study were analyzed with SEM. There are two SEM methods: covariance-based (CB-SEM) and variant-based (PLS-SEM). When deciding which one to be utilized, it’s critical to be aware of the differences between the two (Hair Jr. et al. 2017). CB-SEM aims to “minimize the differences between sample covariance matrix estimates, while PLS_SEM maximizes the explained variance of endogenous constructs” (Hair et al. 2011). Therefore, CB-SEM is mainly used for the confirmation of established theories (explanations); in contrast, PLS-SEM is a prediction-oriented approach, primarily undertaken for exploratory research (Sarstedt et al. 2014).\n\nAlmost all studies using PLS-SEM state that PLS-SEM has advantages over CB-SEM. It can complete formative and reflective measurements. Another advantage is that the samples are not necessarily large. Besides that, it assumes that the samples are not necessarily normally distributed (Hair et al. 2014; Henseler et al. 2009). Because one of the aims of this study is to predict whether THK is an antecedent of attitude, SN, and PBC, this study uses PLS-SEM.\n\nAlthough PLS_SEM has some advantages, it also has disadvantages. PLS-SEM does not have a Goodness-of-Fit (GoF) index. The geometric mean of the communal mean and average R2 can be used as general criteria for GoF (Tenenhaus et al. 2005). The criteria for small, medium, and large effects of GoF are 0.1, 0.25, and 0.36 (Wetzels et al. 2009).\n\n\nResults\n\nThe respondents were surveyed self-administered. To filter respondents to fit the criteria, we used filter/screening questions. The questions asked whether, during the COVID-19 pandemic, the respondents accepted the laid-off family members. Screener questions were intended to avoid respondents from answering irrelevant questions.\n\nOf the 200 questionnaires distributed, 71 respondents completed them (meet the criteria sample and pass the screener question). Therefore 71 questionnaires were analyzed. Of the 71 data analyzed, the respondents were born and raised in the villages of Wanagiri and Tengganan (97.20%) while the rest were not born in the location and live in the villages of Wanagiri and Tengganan due to marriage (2.80%). Table 1 contains information about the respondent’s profile.\n\nA self-administered version of the questionnaire was intended. When employing self-administered questionnaires, researchers encounter challenges since respondents’ answers are more impacted by the clarity of the written words than by the interviewer’s abilities (Zikmund and Babin 2016). Thus, the initial step was to carry out a pilot test after the questionnaire had been compiled. The objectives of the pilot test are to identify: (1) whether there are ambiguous words; (2) whether the instructions given can be understood; (3) whether it is difficult for the respondent to answer; and (4) how long the respondent took the time to fill out the questionnaires. A tiny sample size of three respondents participated in this pilot test. The questionnaires were promptly duplicated and distributed to the respondents after revisions were made in response to the pilot test’s findings.\n\nThe criteria for convergent validity, according to Fornell and Larcker (1981), are that: (1) the factor loading is significant and higher than 0.7; and (2) the Average Variance Extracted (AVE) value is higher than 0.5; whereas for discriminant validity, the AVE value exceeds the squared correlation value between the construct pairs ( Table 3). The composite reliability value is used to evaluate reliability. The cutoff criterion for Composite Reliability is 0.7 (Abdillah and Jogiyanto 2015; Nunnaly in Onofrei et al. 2022).\n\nTable 2 shows that all variables passed the convergent validity test with an AVE value greater than 0.5. Additionally, it has passed the test for discriminant validity, which establishes that each indicator in a latent variable differs from indicators in other latent variables (as shown by a higher loading score in its construct). All variables pass the construct reliability test, as evidenced by the reliability testing results (each variable’s composite reliability is more than 0.7).\n\n\n\n• Sincerity and prayer will expedite my process of utilizing forest land\n\n\n\n• Believing in the law of karma phala will lead me to the forest land utilization\n\n\n\n• Village (customary) leaders care for forest land utilization\n\n\n\n• Collective effort and responsibilities of village (customary) residents and leaders ensure the wise utilization of the forest\n\n\n\n• Forest land utilization provides learning opportunities and enables anticipation of upcoming changes\n\n\n\n• Very Unwise – Very Wise\n\n\n\n• Negative- Positive\n\n\n\n• Very Poor – Very Good\n\n\n\n• Village and/or customary officials will support the sustainable management of customary forests/village forests\n\n\n\n• Other people with whom I interact regularly will perceive the desirability of involvement in the sustainable management of customary village forests\n\n\n\n• I appreciate other people's significant opinions regarding my involvement in the sustainable management of customary/village forests\n\n\n\n• I believe I am knowledgeable enough about sustainable customary/village forest management\n\n\n\n• I have all the necessary labor and knowledge resources to manage village and/or customary forests sustainably\n\n\n\n• When I want to plan sustainable customary/village forest management, I have sufficient technical skills.\n\n\n\n• I intent to get alternative income from sustainable customary/village forests management in the next year?\n\n\n\n• How serious are you in the customary/village forests management in the next year?\n\nFollowing the measurement model, SEM was used to investigate each hypothesis contained within the suggested model. This two-step analytic strategy is consistent with Anderson and Gerbing (1988). The results can be seen in Table 4.\n\nTable 4 shows that all hypotheses are supported by data with a t value greater than the t table; while the relationship between variables shows unilateral results (all path values have positive coefficients).\n\nAfter testing the hypothesis, we calculate the GoF value. If a model does not fit the data, then the data contains more information than the model conveys. Therefore, the prediction is not significant, and the conclusion may be debatable (Henseler et al. 2016). The GoF value in this study is 0.685, which is higher than the large GoF value. Therefore, the proposed model is consistent with the data, and the model tested is parsimonious and reasonable.\n\n\nDiscussion\n\nThe results of this study differ from the findings of research conducted by Yazdanpanah et al (2014) who examined water conservation-related behavior intentions across the Middle East and North Africa; Knussen et al. (2004) who examined intention to recycle household waste in Glasgow, Scotland; Ofoegbu and Speranza (2017) who examine at South Africa’s intention to adopt practical management and sustainable forest usage; where the three reported that at least one of the 3 predictors of behavioral intention in TPB (Attitude, SN and PBC) did not have a significant effect. Accordingly, the results of this study confirmed that the 3 predictors had a positive and significant effect. The findings of this study are consistent with the study conducted by Ajzen (2011) who states that ideally, the 3 predictors have a positive and significant statistical effect; Borges and Lansink (2016) who predicted cattle ranchers’ intentions in Brazil to adopt better natural pastures.\n\nThis study used the TPB model to understand, explain, and predict the behavior of families who receive the arrival of migrants in their areas. It identifies the reason for their willingness to cultivate forests sustainably. This study model includes the THK construct in the TPB model to understand, explain, and predict the behavior of land cultivators due to the impact of COVID-19. When COVID-19 hit, many company workers were laid off so they returned to their hometowns, which consequently more or less put pressure on the families who received their return.\n\nThe TPB model developed in this study shows that social psychological factors (attitudes, SN, and PBC) can explain and predict the intentions and behavior of forest managers. The THK variable included in the TPB model can explain and predict attitudes, SN, and PBC positively and significantly. Adopted values are defined as ideals and guiding principles in human life (Rokeach 1973; Schwartz 1992). Likewise with THK are the values adhered to by the Balinese Hindu community and become the basis for displaying behavior.\n\nAttitudes have a strong impact on people’s perceptions toward the attitude object and thus have an impact on behavior (Fazio 1986). Attitudes can be positive or negative and contain moral beliefs, namely individual beliefs that something is moral or immoral (Eagly and Chaiken 1993; Krosnick and Petty 1995; Skitka et al. 2005). Attitudes have a strong influence on the way humans perceive and understand the world (Fazio 2000; Maio et al. 2019).\n\nBecause values are guiding principles and they are considered to guide our behavior (Sagiv and Roccas 2017) through a series of variables including attitudes (Homer and Kahle 1988), then, the values espoused will influence human feelings towards certain objects or people, which in turn will influence action (Thorne et al. 2020). In this study, the values of THK adhered to by migrant-receiving families can shape their attitudes toward the sustainable forest management. They adhere to the values of THK principles that produce positive manifestations reflected in the continuous management forests sustainably even though they have migrants arriving.\n\nFurthermore, espoused values may vary between individuals depending on their personality, needs, and circumstances (Sheth et al. 1991). Adhered values are felt by individuals and can be shaped and influenced by others as many research results show that individuals are influenced by friends, relatives, co-workers, business partners, or other parties around them (Paul et al. 2016). The results of this study indicate that the perception of migrant-arriving families to THK values is positive. This in turn forms the SN. The family feels that the THK values around them can influence their perception of SN. In this case, the reference group agrees or advises them to continuously carry out sustainable forest management. In other words, the reference group also adheres to THK values and may also sustainably manage forests.\n\nPBC refers to a person’s beliefs about how easy or difficult or possible or impossible it is to perform a particular behavior (Ajzen 1991). Many previous studies often used PBC as an antecedent of various behaviors related to environmental sustainability (Fishbein and Ajzen 2010; Yuriev et al. 2020). PBC contains belief power which is an individual’s belief in the existence of factors that support him to behave. This belief is a consequence of the values held by the individual. The THK values adhered to by migrant-receiving families control their behavior concerning the sustainable forest management. The espoused value is an individual’s belief in the existence of factors that support him to manage forests sustainably. Thus, the espoused THK values can influence attitudes, SN, and PBC, which in turn influence the intention of cultivating forest land sustainably.\n\nThis study has several limitations for further research. First, the data was collected using the cross-sectional method that captures only a specific point in time. Further research may consider the longitudinal method. Second, the samples were collected using a non-probabilistic method which only allows the generalization of results with the same conditions and characteristics. Third, in Government Regulation Number 23 of 2021, social forestry has 5 schemes namely village forests, community forests, community plantation forests, customary forests, and forestry partnerships. This study was exclusively conducted in village forests and customary forest, and future research could be conducted on other schemes of social forestry.\n\nThis study also has some practical implications for managers. Because the THK concept can guide humans in humanizing nature by harmonizing the concepts of God and humans, by socializing, understanding, deepening, and applying the THK concept, awareness will be created to protect nature because nature is part of human beings and God. In other words, in creating community welfare, there is an inseparable relationship between humans and God. A deeper understanding and application of this approach can be ensured by making THK a mandatory content and subject in the primary and secondary education curriculum.\n\nThis study received ethical approval from the Ethics Committee of the Indonesia Open University (Universitas Terbuka Indonesia) following comprehensive review (Protocol Number: B/1571/UN31SPS/PT.01.05/2024, approved on April 19,2024). Due to educational background, cultural norms, and risk perception, verbally informed consent was obtained from all participants prior to their involvement in the study. Participants provided explicit agreement for their response to be published in anonymized form as part of aggregate data analysis. All data collection and management procedures adhered to established ethical guidelines for human subject research.",
"appendix": "Data availability statement\n\nFigshare: Dataset coding responses from Bali-THK respondents (English).xlsx, 10.6084/m9.figshare.27890262.v1 (Patiro et al. 2024).\n\nThis file contains the following underlying data:\n\n* Dataset coding responses from Bali-THK respondents (English).xlsx\n\n* The variable in this file are: Name, Full-time job, Part-time job, Gender, Length of stay, Monthly expenditure, Age, Education, Family members, Social position, Marital status, Tri Hita Karana (5 indicators), Attitude (3 indicators), Social Norm (3 indicators), Perceived Behavioral Control (3 indicators), and Intention (2 indicators).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 Public domain dedication).\n\n\n\n1. Figshare: Tri Hita Karana Questionnaire (Indonesia).docx, 10.6084/m9.figshare.27861828.v1 (Patiro et al. 2024).\n\nThis file is a questionnaire in Bahasa Indonesia.\n\n2. Figshare: Tri Hita Karana Questionnaire (English).docx, 10.6084/m9.figshare.27861894.v1 (Patiro et al. 2024).\n\nThis file is a questionnaire in English.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 Public domain dedication).\n\nThis work did not use standard review methods, hence no reporting guidelines were applied.\n\n\nAcknowledgements\n\nWe extend our sincere gratitude to the Indonesia Open University for their institutional support. We would particularly like to acknowledge Maharani Hapsari, Rahman Kurniadi, Rini Astuti, Pantja Pramudya, Budi Mulyawan, Zaenal Fuad, Ismatul Hakim, Aria Atyanto Satwiko, Rini Hanifa, Caroline Astipranatari, Putu Widiana, and Putu Suarjana for their invaluable contributions to the data collection process. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nZenker S, Kock F: The coronavirus pandemic – A critical discussion of a tourism research agenda. Tour. Manag. 2020; 81(April): 104164. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang H, Song H, Wen L, et al.: Annals of Tourism Research Forecasting tourism recovery amid COVID-19. Ann. Tour. Res. 2021; 87: 103149. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZikmund WG, Babin BJ: Exploring Marketing Research. 11th ed.Massachusetts: Cengage; 2016."
}
|
[
{
"id": "346466",
"date": "30 Jan 2025",
"name": "Sudirman Daeng Massiri",
"expertise": [
"Reviewer Expertise Forest Policy",
"Social forestry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe Covid 19 Pandemic problem has passed 5 years ago and Indonesia has successfully overcome this problem. However, this research predicts the impact of forest sustainability caused by the Covid 19 pandemic, through the application of the Theory of Planned Behaviour (TPB) framework. The application of the TPB theoretical framework in predicting the behavior and intention to manage forests is the novelty of this research.\n\nBackground Authors also need to corroborate with previous research to strengthen whether there is an impact of covid 19 on forest sustainability or on land cover change.\nSample Why were non-migrant recipient communities not interviewed as behavioral controls?. Is there a difference between the community receiving covid 19 migrants and non-migrant recipients?.\nDiscussions Discussions Should strengthening references that confirm whether the covid pandemic increased pressure on forest destruction? Or whether during covid 19 there was an increase in forest product commodities?\n\nThe author should also clarify whether there is a difference in the behavior of communities that accept migrants and communities that do not accept migrants.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1457
|
https://f1000research.com/articles/13-1455/v1
|
02 Dec 24
|
{
"type": "Research Article",
"title": "ARTIFICIAL INTELLIGENCE AND ITS DISRUPTIVE ROLE IN THE SOUTH AFRICAN FINTECH INDUSTRY",
"authors": [
"Priviledge Cheteni",
"Herrison Matsongoni",
"Ikechukwu Umejesi",
"Herrison Matsongoni",
"Ikechukwu Umejesi"
],
"abstract": "Background The emergence of artificial intelligence presents both potential for growth and challenges for the financial industry. This study examines the impact of artificial intelligence (AI) on the South African fintech industry, focusing on its transformative nature.\n\nMethod A purposive sampling technique was used to select 76 participants from the banking sector. Furthermore, the participants were divided into focus groups and interviewed. The thematic analysis conducted in this study revealed eight critical themes that encapsulated the myriad challenges and opportunities faced by industry professionals. From navigating the ever-changing regulatory environment to embracing technological advancements, addressing shifting customer expectations, and cultivating organisational agility and resilience, the financial industry grapples with a complex interplay of factors that demand strategic foresight, adaptability, and a commitment to continuous learning and innovation.\n\nConclusions The results demonstrate that AI is propelling innovation, improving operational efficiency, and transforming customer experience in the finance industry. Nevertheless, substantial impediments have arisen in the form of issues over data protection, talent recruiting, and regulatory ambiguity.",
"keywords": [
"artificial intelligence",
"fintech",
"Economics",
"Finance",
"Banking",
"Development Economics",
"Macroeconomics"
],
"content": "1. Introduction\n\nThe dawn of the digital age has ushered in a new era of innovation, one that is reshaping industries globally. At the forefront of this transformation is the fintech sector, where the seamless integration of cutting-edge technologies promises to revolutionize the way, we interact with financial services (Mazzini & Bagni, 2023). In South Africa, the fintech landscape is undergoing a seismic shift driven by the rapid adoption of Artificial Intelligence (AI). This technological marvel, once the domain of science fiction, has become a reality, poised to transform the nation’s financial ecosystem from the ground up (Ekinci, 2021; Aromolaran, Ngepah & Saba, 2024). AI, with its ability to process vast amounts of data, identify patterns, and make sophisticated decisions, is already making waves in the financial sector, offering a plethora of opportunities to enhance efficiency, improve customer experiences, and unlock new growth avenues (Kuiper, van den Berg, van der Burgt & Leijnen, 2022).\n\nFrom fraud detection and risk management to personalised investment advice and credit scoring, AI has revolutionised the way financial institutions operate (Dzingirai, 2023). Its advanced algorithms can shift through vast troves of data, identifying patterns and anomalies that might indicate fraudulent activities and enabling proactive measures to protect institutions and consumers (Mangena & Sithole, 2024). Moreover, AI-powered risk management systems can analyse complex financial data, market trends, and economic indicators, providing valuable insights to guide strategic decision-making and mitigate potential risks. This increased efficiency and accuracy in risk assessment safeguard financial institutions and fosters greater consumer confidence in the sector.\n\nOne of the most significant impacts of AI in South African fintech is the realm of customer experience. Traditional banking models, often plagued by long queues, complex paperwork, and bureaucratic processes, are being challenged by AI-powered solutions that offer seamless, personalised, and efficient services (Qwabaza, 2020). Chatbots and virtual assistants powered by AI are becoming the new face of customer service, providing 24/7 support and addressing inquiries with remarkable accuracy (Kuiper et al., 2022). These intelligent systems can understand natural language and learn from each interaction, continuously improving their ability to better serve customers. Furthermore, AI-driven personalisation algorithms can analyse customer preferences, behavioural patterns, and financial goals, tailoring product recommendations and services to meet individual needs, thereby enhancing customer satisfaction and loyalty.\n\nHowever, AI integration in the fintech sector is challenging. Concerns over data privacy, algorithmic bias, and the potential displacement of human workers must be addressed through robust governance frameworks and ethical guidelines (Mazzini & Bagni, 2023). As AI systems become more sophisticated and autonomous, ensuring transparency, accountability, and fairness in their decision-making processes is paramount (Gigante & Zago, 2023). Regulatory bodies and industry stakeholders must collaborate to establish clear guidelines and standards safeguarding consumer rights while fostering innovation.\n\nAdditionally, the responsible development and deployment of AI in fintech requires a skilled workforce with the necessary technical expertise and ethical understanding (Mangena & Sithole, 2024). Investing in education and training programs that bridge the gap between AI technology and its practical applications in the financial sector is crucial for ensuring a smooth and sustainable transition (Kuiper et al., 2022). Thus, by nurturing a talent pool proficient in AI and its ethical implications, South Africa can position itself as a hub for responsible fintech innovations.\n\nAs South Africa navigates this AI-driven transformation, collaboration between the public and private sectors, regulators, and industry stakeholders is crucial (Dzingirai, 2023; Mhlanga, 2023). Thus, by fostering an environment that encourages innovation while prioritising consumer protection and responsible AI development, a nation can harness the full potential of this revolutionary technology. Through a balanced approach that embraces the opportunities presented by AI while mitigating its risks, South Africa’s fintech industry can thrive, offering cutting-edge solutions that enhance financial accessibility, promote economic growth, and elevate citizens’ overall quality of life.\n\nThis study’s primary objective is to explore AI’s transformative role in shaping South Africa’s fintech landscape. This study delves into how AI revolutionizes the financial sector, from fraud detection and risk management to personalised investment advice and credit scoring. It highlights how the seamless integration of AI-powered solutions enhances efficiency, improves customer experiences, and unlocks new avenues for growth in the South African fintech industry. This study aims to provide a comprehensive understanding of the various applications of AI in the fintech sector and its immense potential in driving financial inclusion, democratising access to sophisticated financial services, and fostering national economic development.\n\nWhile the study extensively covers the transformative potential of AI in South Africa’s fintech sector, it also acknowledges the challenges that must be addressed to ensure responsible and ethical development and deployment of this technology. This article highlights concerns over data privacy, algorithmic bias, and the potential displacement of human workers, which require robust governance frameworks and clear guidelines to be effectively mitigated. Additionally, this study identifies the need to bridge the gap between AI technology and its practical applications in the financial sector by investing in education and training programs that nurture a skilled workforce proficient in AI and its ethical implications. This gap underscores the importance of a collaborative approach involving public and private sectors, regulators, and industry stakeholders to establish a balanced and sustainable ecosystem for AI-driven fintech innovation in South Africa.\n\n\n2. The transformative power of AI in South African fintech\n\nRapid advancements in Artificial Intelligence (AI) have revolutionised the financial sector, transforming how South African fintech companies operate and deliver services to their customers. With its ability to process vast amounts of data, identify patterns, and make sophisticated decisions, AI has become a driving force behind the evolution of the fintech industry (Mhlanga, 2023). This technological marvel, once confined to science fiction, has become a tangible reality poised to reshape the nation’s financial ecosystem from the ground up (Ekinci, 2021).\n\nThe heart of this AI-driven transformation lies in the fintech sector, a dynamic and rapidly growing industry that leverages cutting-edge technologies to redefine the traditional financial landscape (Nowakowski & Waliszewski, 2022). In South Africa, the fintech landscape is undergoing a seismic shift as AI-powered solutions are being integrated into various financial services, from fraud detection and risk management to personalised investment advice and credit scoring (Qwabaza, 2020). This seamless integration of AI not only enhances efficiency but also improves customer experience and unlocks new growth opportunities for financial institutions (Irfan, Elmogy & El-Sappagh, 2023).\n\nOne of the most significant impacts of AI in South African fintech is fraud detection and risk management. AI’s advanced algorithms can shift through vast troves of financial data and identify patterns and anomalies that might indicate fraudulent activities. This capability enables proactive measures to protect both financial institutions and consumers, instilling greater confidence in the sector (Mazzini & Bagni, 2023). Moreover, it analyzes complex financial data, market trends, and economic indicators, providing valuable insights to guide strategic decision-making and mitigate potential risks (Nyugha, 2024).\n\nThe integration of AI in South African fintech is also transforming the customer experience (Giwa & Ngepah, 2024). Traditional banking models, often plagued by long queues, complex paperwork, and bureaucratic processes, are challenged by AI-powered solutions that offer seamless, personalised, and efficient services. Chatbots and AI-powered virtual assistants are becoming the new face of customer service, providing 24/7 support and addressing inquiries with remarkable accuracy (Irfan et al., 2023). These intelligent systems can understand natural language and learn from each interaction, continuously improving their ability to serve customers better (Dzingirai, 2023).\n\nFurthermore, AI-driven personalisation algorithms have revolutionised the way financial services are tailored to individual needs (Mangena & Sithole, 2024). Thus, by analysing customer preferences, behavioural patterns, and financial goals, these algorithms can provide personalised product recommendations and services that enhance customer satisfaction and loyalty. This shift towards hyper-personalization improves the overall customer experience and fosters deeper relationships between financial institutions and their clients (Irfan et al., 2023).\n\nIn investment and wealth management, AI is poised to democratise access to sophisticated financial advice (Aromolaran et al., 2024). Robo-advisors, powered by AI, can analyze market trends, individual risk profiles, and investment goals, providing personalized portfolio recommendations tailored to each client’s unique needs (Kuiper et al., 2022). These AI-driven advisory tools not only offer cost-effective solutions but also enable individuals with diverse financial backgrounds to access professional-grade investment guidance, level the playing field, and promote financial literacy across South African society.\n\nMoreover, AI has played a pivotal role in expanding financial inclusion in South Africa. By using alternative data sources, such as mobile phone records, utility bills, social media activity, and advanced analytics, AI can assess creditworthiness more accurately (Qwabaza, 2020; Nyugha, 2024). This enables financial institutions to extend services to underserved communities and individuals who may have been overlooked due to limited credit histories or traditional scoring methods (Nowakowski & Waliszewski, 2022). Thus, by leveraging AI’s ability to identify patterns and extract insights from non-traditional data sources, fintech companies can develop innovative credit scoring models, fostering greater access to financial services, and empowering economic growth across all segments of society.\n\nThe transformative impact of AI in South African fintech extends beyond the realms of customer experience and financial inclusion (Dzingirai, 2023). AI-powered solutions are also revolutionising the way financial institutions operate, enhancing efficiency, and streamlining internal processes (Maple, Szpruch, Epiphaniou, Staykova, Singh, Penwarden & Avramovic, 2023). By automating repetitive tasks to optimise resource allocation, AI enables financial institutions to focus on strategic priorities, reduce operational costs, and increase productivity.\n\nAdditionally, integrating AI into South African fintech paves the way for developing innovative financial products and services. By leveraging AI’s analytical capabilities of AI, fintech companies can gain deeper insights into market trends, customer preferences, and emerging financial needs. This knowledge can then be translated into the creation of tailored financial solutions that cater to the diverse and evolving requirements of the South African market, further strengthening the nation’s fintech ecosystem (Mhlanga, 2023).\n\nAI’s transformative power in South African fintech is undeniable. From fraud detection and risk management to personalised investment advice and credit scoring, this technological marvel is reshaping the financial sector, driving efficiency, improving customer experiences, and fostering financial inclusion (Qwabaza, 2020). As the fintech industry continues to evolve, the strategic integration of AI will play a crucial role in shaping the future of finance in South Africa, positioning the nation as a hub for responsible and innovative fintech solutions (Giwa & Ngepah, 2024).\n\nAlthough integrating Artificial Intelligence (AI) in the South African fintech sector has been transformative, it is not without its challenges. As this revolutionary technology has become more sophisticated and autonomous, concerns over data privacy, algorithmic bias, and the potential displacement of human workers have come to the forefront, requiring careful consideration and proactive measures to address them.\n\nData privacy is one of the primary concerns surrounding integrating AI into fintech (Aromolaran et al., 2024). As AI systems rely on vast amounts of data to function effectively, there are valid concerns about protecting sensitive financial information and the potential misuse of such data (Cloete, 2024). Regulatory bodies and industry stakeholders must collaborate to establish clear guidelines and standards safeguarding consumer rights while fostering innovation in the fintech sector.\n\nAnother crucial challenge is algorithmic bias. AI systems, while designed to make objective and data-driven decisions, can inadvertently perpetuate or even amplify existing societal biases (Nowakowski & Waliszewski, 2022; Maple et al., 2023). This can have far-reaching consequences, particularly in the financial sector, where decisions regarding credit, investments, and access to services can significantly impact individuals and communities (Irfan et al., 2023). Addressing algorithmic bias requires a multifaceted approach involving rigorous testing, continuous monitoring, and implementation of fairness-enhancing algorithms (Mishra, 2023).\n\nThe potential displacement of human workers is another concern that must be addressed as AI becomes more prevalent in the fintech industry. While AI-powered solutions can enhance efficiency and productivity, there is a legitimate fear that certain job roles may become obsolete or significantly transformed (Mazzini & Bagni, 2023). To mitigate this challenge, financial institutions and policymakers must collaborate to develop comprehensive strategies that prioritise the reskilling and upskilling of the workforce, ensuring a smooth transition and the creation of new employment opportunities.\n\nEnsuring the transparency and accountability of AI-driven decision-making processes is a critical challenge in the South African fintech sector. As AI systems become more autonomous, it is essential to establish precise mechanisms to explain and justify the decisions made by these systems (Mangena & Sithole, 2024). This transparency is crucial for building trust and ensuring that AI-powered financial services align with ethical principles and regulatory requirements (Gigante & Zago, 2023).\n\nThe responsible development and deployment of AI in fintech also require a skilled workforce with technical expertise and ethical understanding. Investing in education and training programs that bridge the gap between AI technology and its practical applications in the financial sector is crucial for ensuring a smooth and sustainable transition. Thus, by nurturing a talent pool proficient in AI and its ethical implications, South Africa can position itself as a hub for responsible fintech innovations.\n\nRegulatory frameworks and governance structures are pivotal in addressing the challenges associated with AI integration in the South African fintech sector (Giwa & Ngepah, 2024). Policymakers must collaborate with industry stakeholders to develop comprehensive guidelines and standards that balance fostering innovation and safeguarding consumers’ rights. This collaborative approach is essential to ensure AI-powered fintech solutions’ responsible and ethical development.\n\nAnother critical challenge is effective collaboration between public and private sectors, regulators, and industry stakeholders (Nyugha, 2024). By fostering an environment that encourages innovation while prioritising consumer protection and responsible AI development, South Africa can harness the full potential of this revolutionary technology (Mhlanga, 2023). This collaborative approach is crucial for addressing multifaceted challenges and ensuring a sustainable future for AI-driven fintech in the nation.\n\nIntegrating AI into the South African fintech sector raises questions about the ethical implications of this technology. As AI systems become more autonomous and make decisions that directly impact people’s financial well-being, ensuring that these decisions align with ethical principles such as fairness, non-discrimination, and accountability (Nowakowski & Waliszewski, 2022). Developing comprehensive ethical guidelines and frameworks for using AI in fintech is a pressing challenge that needs to be addressed.\n\nOvercoming the challenges associated with AI integration in the South African fintech sector requires a multifaceted and collaborative approach. Thus, by addressing concerns over data privacy, algorithmic bias, workforce displacement, transparency, and ethical implications, a nation can unlock the full potential of AI while ensuring a responsible and sustainable fintech ecosystem. This holistic approach, driven by the collective efforts of regulators, financial institutions, and industry stakeholders, is crucial for positioning South Africa as a leader in AI’s responsible and innovative application in the fintech industry.\n\nThe study of this topic can be grounded in several critical theoretical frameworks and concepts, including Systems Theory. The Systems Theory has a rich and diverse background, tracing its origins in the early 20th century and the work of the biologist Ludwig von Bertalanffy (Whitchurch & Constantine, 1993). Bertalanffy proposed a general systems theory to understand living organisms as integrated wholes, challenging the prevailing reductionist approach that views systems as simply the sum of their parts. This perspective marked a significant shift in understanding complex phenomena, moving away from the traditional focus on individual components and toward a more holistic and interconnected understanding of the system as a whole (Von Bertalanffy, 1972).\n\nAt the core of Systems Theory is a holistic perspective emphasising the importance of understanding the whole system rather than just its individual components (Von Bertalanffy, 1972). This approach recognises the interdependence of the elements of the system, where changes in one part can have ripple effects on other parts, leading to nonlinear and often unexpected outcomes. Systems Theory also highlights emergent properties, which arise from complex interactions within the system and cannot be fully explained by examining individual parts alone. These emergent properties are a testament to the inherent complexity of systems and the limitations of reductionist approaches in capturing the full breadth and depth of the phenomena under study. Furthermore, Systems Theory acknowledges the presence of feedback loops, in which the system’s outputs influence its inputs, creating dynamic and self-regulating behaviours. This perspective also highlights the adaptability of systems, as they have the capacity to evolve and respond to changes in their environment through self-organization and learning (Sony & Naik, 2020).\n\nApplying Systems Theory as a guiding framework for studying the role of AI in the financial sector is particularly well-suited because it can be viewed as a complex, interconnected system. Adopting this theoretical foundation, this study captures the holistic nature of the financial industry by considering the various components, stakeholders, and their interdependent relationships.\n\nThis approach enabled researchers to move beyond simplistic cause-and-effect explanations and better understand the system’s intricate workings and the dynamic interplay between its elements. Systems Theory enabled this study to explore the emergent properties and non-linear dynamics that arise from the complex interactions of AI, technology, regulations, customer behaviours, talent management, and other factors within the financial system. It also facilitates the analysis of the feedback loops and adaptive behaviours that shape the evolution and transformation of the financial system over time, providing invaluable insights into the system’s resilience and capacity for self-organisation.\n\nCrucially, this theoretical foundation allowed this study to develop a more comprehensive understanding of the financial system’s response to the integration and impact of AI technologies. Considering the system as a whole, rather than focusing on isolated components, researchers can gain a deeper appreciation of the system’s holistic adaptations and ability to maintain core functions and characteristics in the face of technological disruptions. This holistic perspective was invaluable in gaining a deeper, more nuanced understanding of the topic, as it enabled researchers to uncover the underlying patterns, trends, and interdependencies that shape the financial system’s behaviour and transformation in the age of AI.\n\n\n3. Methods\n\nThe research design for this study followed a qualitative approach, utilising focus group discussions as the primary data collection method. This approach was selected to gain a deep, contextual understanding of the phenomenon under investigation, drawing on the lived experiences and perspectives of the participants (Braun, Clarke, Boulton, Davey & McEvoy, 2020).\n\nThe target population for this study consisted of individuals working in the financial industry. This specific population was chosen because of its direct involvement and expertise in the subject matter, which is expected to provide rich and insightful data for analysis. A total of 76 participants from the financial industry were selected using a purposive sampling technique. This non-probability sampling method allows researchers to identify and recruit participants with the necessary knowledge, experience, and characteristics relevant to the research objectives (Brown & Rogers, 2020). The participants were organised into 12 focus group discussions, each comprising six individuals. This group size was optimal for facilitating in-depth discussions, encouraging active participation, and ensuring a balanced representation of diverse perspectives (Crabtree & Miller, 2023).\n\nThe data collected from the focus group discussions were analysed using a thematic analysis approach. This analytical method involves the systematic identification, organisation, and interpretation of recurring patterns and themes within the data (Braun & Clarke, 2022). The thematic analysis allows researchers to uncover the core concepts, underlying meanings, and critical insights that emerge from participants’ narratives and experiences (Brown & Rogers, 2020).\n\nThis study followed ethical research protocols. The work has been authorised by the University Research Ethics Committee (REC-270710-028-RA Level 01). The participants were given an informed consent form that explained the objective of the study, the voluntary nature of their participation, and the steps taken to protect the confidentiality and anonymity of their responses. The researchers took measures to guarantee the secure storage of the acquired data, and any potentially identifiable information was eliminated or made anonymous to safeguard the privacy of the participants (Braun, Clarke, Boulton, Davey & McEvoy, 2020).\n\n\n4. Findings\n\nThematic analysis of the focus group discussions revealed eight key themes that provided insights into the experiences and perspectives of the participants from the financial industry. These themes offer a comprehensive understanding of the subject matter and shed light on the complex dynamics that shape the phenomenon under investigation.\n\n4.1.1 Evolving regulatory landscape\n\nThe participants highlighted the significant impact of the ever-changing regulatory environment on their daily operations and decision-making processes. They emphasized the need for agility and adaptability in navigating dynamic regulatory landscapes.\n\nFocus group discussion 1: “The constant changes in regulations require us to be constantly on our toes. We have to stay up-to-date with the latest requirements and ensure that our processes are aligned accordingly.”\n\nFocus group discussion 4: “Compliance has become a critical focus. We spend a substantial amount of time and resources ensuring we are meeting the regulatory standards, which can be challenging given the pace of change.”\n\nFocus group discussion 3: “Regulatory uncertainty is one of the biggest challenges that we face. It makes it difficult to plan and implement long-term strategies, as we never know when the next round of changes might come.”\n\nThe research findings underscore the significant influence of the constantly evolving regulatory landscape on the financial industry. Participants emphasized the critical need for adaptability, compliance, and strategic agility to effectively navigate this dynamic regulatory environment. Financial institutions and professionals must remain vigilant and proactive in monitoring regulatory changes; interpreting new rules and guidelines; and rapidly adjusting their policies, procedures, and business practices accordingly.\n\nA key concern that emerged from the findings is the lack of regulatory certainty, which poses considerable challenges for long-term planning and decision making within the financial sector. The unpredictable nature of regulatory shifts makes it difficult for firms to confidently chart a stable forward-looking strategy. This uncertainty can hinder innovation, investment, and the ability to rapidly respond to market opportunities. As the regulatory framework continues to evolve, financial organizations need to develop robust mechanisms for scenario planning, risk assessment, and organizational agility to thrive in an environment of constant change.\n\n4.1.2 Technology-driven transformation\n\nParticipants discussed the transformative impact of technological advancements on the financial industry, ranging from the adoption of digital platforms to the integration of innovative tools and solutions.\n\nFocus group discussion 4: “Technology has revolutionized the way we operate. From automated processes to data-driven decision-making, it has empowered us to be more efficient and responsive to client needs.”\n\nFocus group discussion 6: “The pace of technological change is dizzying. We are constantly evaluating and implementing new tools and systems to remain competitive and meet the evolving expectations of our customers.”\n\nFocus group discussion 9: “Embracing technology is crucial for us to remain relevant in the market. However, this also brings challenges in terms of data security, talent acquisition, and managing the transition.”\n\nThe research findings clearly indicate that technology-driven transformation is a central and pervasive force that shapes the financial industry. The study participants recognized the significant benefits and opportunities that technological advancements have brought to the sector, including improved operational efficiency, more data-driven and informed decision-making, and enhanced customer experiences. Innovative technologies, such as cloud computing, artificial intelligence, and mobile banking, have enabled financial institutions to streamline processes, gain deeper data-driven insights, and deliver more personalized and convenient services to their clients.\n\nHowever, the findings also highlight the considerable challenges associated with the rapid pace of technological change in the financial industry. Concerns regarding data security, cybersecurity threats, and the need for robust data governance frameworks have emerged as key issues. Additionally, the ability to attract, develop, and retain top technology talent is cited as a major hurdle, as financial firms compete with tech companies for in-demand skills. Managing the organizational transformation and cultural shift required to fully capitalize on new technologies is another significant challenge noted by the participants. As the technological landscape continues to evolve, financial organizations need to prioritize agility, digital expertise, and a culture of innovation to effectively navigate this digital transformation.\n\n4.1.3 Shifting customer expectations\n\nThe participants discussed the evolving expectations and demands of their customers, which are driving the industry to adapt and innovate to remain competitive and relevant.\n\nFocus group discussion 7: “Customers today are more informed, tech-savvy, and have higher expectations than ever before. They want personalized, seamless, and digitally enabled services, and we have to constantly strive to meet and exceed those expectations.”\n\nFocus group discussion 8: “The rise of fintech companies has disrupted the traditional financial service landscape. Customers now have more choices and are more willing to explore alternative providers that offer innovative solutions and a superior customer experience.”\n\nFocus group discussion 9: “Maintaining customer loyalty has become increasingly challenging. We have to continuously invest in understanding customers’ changing needs and preferences and adapt our offerings accordingly.”\n\nThe research findings clearly underscore the significant shift in customer expectations within the financial industry. The participants highlighted the growing demand from consumers for personalized, technology-driven, and seamlessly integrated customer experiences. The rise of fintech companies and digital-native financial service providers has raised the bar, introducing new competition and heightening customer expectations across the sector. Traditional financial institutions are now under increased pressure to adapt and innovate to remain relevant and competitive in this evolving landscape.\n\nMaintaining customer loyalty has emerged as a critical priority for financial organizations, requiring a deeper understanding of evolving customer needs, preferences, and behaviors. Today, customers expect intuitive and omni-channel experiences, real-time access to information and services, and personalized product and service recommendations. To meet these expectations, financial firms must invest in technologies, such as mobile banking, artificial intelligence, and data analytics, to gain a more granular, data-driven understanding of their customer base. Adapting organizational structures, processes, and talent to deliver these heightened customer expectations will be a key differentiator for financial institutions seeking to thrive in this new era of customer-centric financial services.\n\n4.1.4 Talent acquisition and retention challenges\n\nParticipants expressed concerns about the difficulties in attracting, developing, and retaining skilled talent, which is crucial for the industry’s continued growth and innovation.\n\nFocus group discussion 10: “Finding and retaining the right talent with the necessary skills and expertise has become a major challenge. The competition for top talent is fierce, and we often struggle to offer competitive compensation and career development opportunities.”\n\nFocus group discussion 12: “The rapid technological changes in the industry require a constant upskilling of our workforce. Keeping employees’ knowledge and skills up-to-date is an ongoing battle, and it is crucial for maintaining our competitive edge.”\n\nFocus Group Discussion 11: “Fostering a culture of innovation and entrepreneurship is essential, but it is a delicate balance. There is a need to strike the right balance between maintaining operational efficiency and encouraging risk-taking and creativity among our employees.”\n\nThe findings highlight the significant challenges faced by the financial industry in attracting, developing, and retaining skilled talent. Participants emphasized fierce competition for top talent, particularly in fields such as data science, cybersecurity, and financial technology. As industry undergoes rapid technological transformation, the need for professionals with cutting-edge digital and analytical skills has become paramount. Traditional financial institutions must compete with each other, as well as with tech companies and startups, which can often offer more attractive compensation and career development opportunities.\n\nCompounding this challenge is the constant need for continuous upskilling and professional development in the financial workforce. To keep pace with evolving technologies, regulatory changes, and shifting customer demands, financial organizations must invest heavily in training and reskilling programmes. Cultivating a culture that nurtures innovation, entrepreneurship, and continuous learning has become a critical imperative. Failure to address these talent-related issues poses a serious threat to the financial industry’s ability to drive growth, remain competitive, and adapt effectively to rapidly evolving market dynamics. Financial firms that can successfully attract, develop, and retain the right mix of digital savvy and forward-thinking talent will be best positioned to thrive in the future.\n\n4.1.5 Embracing sustainability and social responsibility\n\nParticipants discussed the increasing importance of incorporating sustainability and social responsibility into their business practices, driven by both regulatory requirements and shifting stakeholder expectations.\n\nFocus group discussion 10: “Sustainability has become a key focus area. We are actively investing in initiatives that reduce the environmental footprint and contribute to a more sustainable future for our industry and the communities we serve.”\n\nFocus group discussion 12: “Integrating social responsibility into our operations is no longer an option but a necessity. Stakeholders, including investors, regulators, and customers, are demanding that we demonstrate our commitment to ethical and socially conscious practices.”\n\nFocus group discussion 11: “Balancing financial performance with environmental and social impacts is a constant challenge. We have to carefully navigate the trade-offs and find ways to create long-term value for all our stakeholders.”\n\nThe research findings reveal the growing importance of sustainability and social responsibility as critical priorities in the financial industry. Participants highlighted the need for financial institutions to not only focus on financial performance but also address environmental concerns, contribute to social well-being, and demonstrate a clear commitment to ethical business practices. This shift is driven by a combination of regulatory requirements and the evolving expectations of various stakeholders, including investors, customers, and the broader community in which these organizations operate.\n\nAchieving the right balance between financial performance and positive social and environmental impacts has emerged as a key challenge in the industry. Financial firms must navigate complex tradeoffs and find innovative ways to integrate sustainability considerations into their core business strategies, product offerings, and operational models. This may involve developing sustainable financial solutions, investing in green initiatives, promoting financial inclusion, and strengthening corporate governance and transparency. As scrutiny and demands for corporate social responsibility continue to intensify, the financial industry will need to prioritize and embed sustainability as a fundamental pillar of its long-term value proposition. Those who can successfully navigate this balance will be better positioned to maintain the trust and loyalty of their stakeholders while contributing to a more sustainable and equitable future.\n\n4.1.6 Data-driven decision-making and analytics\n\nThe participants emphasized the critical role of data and analytics in driving informed decision-making and gaining a competitive edge in the rapidly changing financial landscape.\n\nFocus group discussion 1: “Data have become the lifeblood of our industry. We rely on advanced analytics to gain insights into market trends, customer behaviour, and risk factors, which are essential for making strategic and tactical decisions.”\n\nFocus group discussion 2: “The ability to harness and analyze data effectively is a major differentiator. We are constantly exploring new ways to leverage data-driven insights to improve our products, services, and overall business performance.”\n\nFocus group discussion 3: “Data privacy and security are paramount concerns, as we delve deeper into data-driven decision-making. Ensuring the responsible and ethical use of data is a top priority for us.”\n\nThe research findings clearly highlight the pivotal role of data and analytics in the financial industry’s decision-making processes. Participants recognized the immense value of data-driven insights in understanding market dynamics, customer behavior, and risk factors, all of which are crucial for informing strategic and operational decisions within financial organizations. The ability to effectively leverage data and analytics has emerged as a key competitive advantage in the rapidly evolving financial landscape, empowering institutions to gain deeper, more granular insights to drive business growth and mitigate risks.\n\nAt the same time, the participants emphasized the critical importance of data privacy and security, underscoring the need for responsible and ethical data management practices. As financial firms amass vast amounts of sensitive customer and market data, they must navigate an increasingly complex regulatory environment and heighten expectations of data protection and governance. Implementing robust cybersecurity measures, ensuring data privacy compliance, and cultivating a culture of data stewardship are essential for financial organizations seeking to harness the power of data and analytics while maintaining the trust of their stakeholders. Those that can strike the right balance between data-driven decision-making and responsible data management will be well-positioned to thrive in the data-intensive future of the financial industry.\n\n4.1.7 Collaboration and ecosystem partnerships\n\nThe participants discussed the growing importance of collaboration and ecosystem partnerships in driving innovation and in addressing the complex challenges facing the financial industry.\n\nFocus group discussion 5: “Collaboration with fintech companies, technology providers, and competitors has become essential for us to stay ahead of the curve. By combining our respective strengths and expertise, we can develop innovative solutions that better serve customers.”\n\nFocus group discussion 7: “Building a robust ecosystem of partners is crucial for accessing new technologies, talent, and market opportunities. We are constantly exploring ways to forge strategic alliances that can enhance our capabilities and fuel our growth.”\n\nFocus group discussion 9: “Navigating the complexities of ecosystem partnerships can be challenging. Aligning objectives, sharing risks and rewards, and maintaining trust are critical factors that must be managed carefully.”\n\nThe research findings suggest that collaboration and ecosystem partnerships have become strategically imperative in the financial industry. Participants recognized the significant value of leveraging complementary strengths and expertise through partnerships with fintech companies, technology providers, and competitors. Collaborative efforts are essential for driving innovation, accessing new technologies and talent, and expanding market opportunities in an increasingly dynamic and competitive landscape. Thus, by tapping into the specialized capabilities and agile mindsets of ecosystem partners, financial institutions can enhance their own offerings, improve customer experiences, and stay ahead of the curve.\n\nHowever, the participants also highlighted the complexities involved in effectively managing these partnerships. Aligning objectives, sharing risks and rewards, and maintaining trust among ecosystem partners are critical challenges. Financial institutions must navigate delicate balancing acts, ensuring that their partnerships generate mutual benefits while preserving their core competencies and competitive advantages. Developing a collaborative culture, establishing clear governance frameworks, and fostering transparent communication are crucial for financial organizations to successfully leverage the power of their ecosystems. Those that can master the art of collaboration will be better positioned to drive transformative innovation and capitalize on emerging market opportunities in the years ahead.\n\n4.1.8 Organizational agility and resilience\n\nThe participants emphasized the need for financial institutions to cultivate organizational agility and resilience to navigate the rapidly changing industry landscape and respond effectively to emerging challenges and opportunities.\n\nFocus group discussion 5: “The pace of change in our industry is breathtaking. We have to be nimble and adaptable, constantly evaluating our strategies, structures, and processes to ensure we can pivot quickly in response to market shifts.”\n\nFocus group discussion 6: “Resilience is not just about weathering storms, but also about being able to bounce back stronger. We are investing in building a culture of innovation, employee empowerment, and continuous learning to enhance our overall organizational resilience.”\n\nFocus group discussion 8: “Balancing short-term performance with long-term sustainability is delicate. We must find ways to drive immediate results while laying the foundation for future growth and adaptability.”\n\nThe findings underscore the critical importance of cultivating organizational agility and resilience within the financial industry. Participants emphasized the need for financial institutions to be nimble, adaptable, and responsive to rapid changes and emerging challenges in the market. This requires a combination of strategic foresight, operational flexibility, and culture that nurtures innovation, employee empowerment, and continuous learning. The participants also highlighted the challenge of striking the right balance between short-term performance and long-term sustainability, recognizing the need to drive immediate results while simultaneously investing in the organization’s ability to adapt and thrive in the face of future disruptions.\n\nThe evolving regulatory landscape has been the subject of extensive research in the financial industry. Corroborating participants’ observations, Mazzini and Bagni (2023) highlight the significant impact of regulatory changes on operational processes and decision-making within financial institutions. Nowakowski and Waliszewski (2022) further emphasized the challenges posed by regulatory uncertainty, echoing participants’ concerns regarding long-term strategic planning. Moreover, Rabbani et al. (2023) underscored the need for agility and adaptability in navigating a dynamic regulatory environment, aligning with the participants’ emphasis on these qualities.\n\nThe transformative impact of technology on the financial industry has been well-documented in the literature. Dzingirai (2023) highlighted the revolutionary effects of digital platforms, automated processes, and data-driven decision-making tools that resonate with participants’ experiences. Garcia (2020, 2023) reinforced the importance of embracing technological advancements to remain competitive and meet evolving customer expectations. However, scholars such as Mangena and Sithole (2024) also acknowledge the challenges associated with rapid technological change, such as data security concerns, talent acquisition, and organizational transitions, echoing participants’ observations.\n\nShifting customer expectations have been a driving force in the financial industry, as highlighted by various researchers. Mangena and Sithole (2024) emphasized the growing demand for personalized, seamless, and digitally enabled financial services, aligning with the participants’ observations. Davis (2020) further underscores the disruptive impact of fintech companies, which have raised the bar for customer experiences and introduced new competition, resonating with participants’ concerns regarding maintaining customer loyalty and providing innovative solutions.\n\nThe challenges related to talent acquisition and retention have been extensively studied in financial industry literature. Riani (2023) corroborates the participants’ experiences, citing fierce competition for top talent and the need for continuous upskilling as major obstacles. Qwabaza (2020) emphasizes the importance of cultivating a culture that fosters innovation and encourages entrepreneurial mind-sets, echoing participants’ observations regarding the need to strike a balance between operational efficiency and nurturing risk-taking and creativity among employees.\n\nThe growing importance of sustainability and social responsibility in the financial industry is reflected in existing literature. The findings support Aromolaran et al. (2024), highlighting the increasing emphasis on integrating sustainability practices into business operations driven by regulatory requirements and stakeholder expectations. Maple et al. (2023) further acknowledge the challenge of balancing financial performance with environmental and social impacts, resonating with participants’ concerns about navigating these trade-offs and creating long-term value for all stakeholders.\n\nData-driven decision-making and analytics have emerged as critical components in the financial industry, as evidenced in the literature. Cloete (2024) reinforces participants’ emphasis on leveraging advanced analytics to gain insights into market trends, customer behaviour, and risk factors. Nyugha (2024) further underscores the competitive advantage conferred by the ability to effectively harness and analyze data, aligning with the participants’ observations. However, Mishra (2023) also highlighted the paramount importance of data privacy and security, echoing participants’ concerns about responsible and ethical data management practices.\n\nScholars have recognized the role of collaboration and ecosystem partnerships in driving innovation and addressing complex challenges in the financial industry. Mhlanga (2023) emphasized the value of strategic alliances and partnerships with fintech companies, technology providers, and competitors in accessing new technologies, markets, and talent pools. Irfan et al. (2023) further acknowledged the complexities involved in managing these partnerships, echoing the participants’ emphasis on aligning objectives, sharing risks and rewards, and maintaining trust among partners.\n\nThe need for organizational agility and resilience in the financial industry has been widely discussed in the literature. Ekinci (2021) emphasized the importance of cultivating organizational agility to navigate rapid changes and respond effectively to market shifts. Mazzini and Bagni (2023) further reinforce the role of resilience in enabling financial institutions to withstand challenges and bounce back stronger, aligning with participants’ emphasis on fostering a culture of innovation, employee empowerment, and continuous learning.\n\nAchieving a delicate balance between short-term performance and long-term sustainability is a critical challenge acknowledged by scholars in this field. Nowakowski and Waliszewski (2022) stressed the need to drive immediate results while simultaneously investing in an organization’s ability to adapt and thrive in the face of future disruptions. This underscores the importance of strategic foresight and operational flexibility in navigating the rapidly changing financial industry.\n\nThe findings of the thematic analysis can be further understood through the lens of systems theory, which provides a holistic perspective on the complex and interconnected nature of the financial industry. The financial industry can be viewed as a dynamic system where various elements, including regulatory changes, technological advancements, customer expectations, talent management, sustainability considerations, data analytics, and ecosystem partnerships, are all interdependent and influence one another. From a systems perspective, the financial industry can be viewed as a complex, adaptive system in which various stakeholders interact and contribute to the overall dynamics of the system. The ability of financial institutions to effectively manage these interconnections and leverage the synergies between different elements is crucial for driving sustainable growth and maintaining a competitive edge in the industry.\n\n\n5. Conclusion\n\nThe financial industry is undergoing a profound transformation driven by a confluence of forces that reshape the landscape in unprecedented ways. The thematic analysis conducted in this study revealed eight critical themes that encapsulated the myriad challenges and opportunities faced by industry professionals. From navigating the ever-changing regulatory environment to embracing technological advancements, addressing shifting customer expectations, and cultivating organizational agility and resilience, the financial industry is grappling with a complex interplay of factors that demand strategic foresight, adaptability, and a commitment to continuous learning and innovation.\n\nWhile the challenges are formidable, the findings also highlight the potential for collaboration, ecosystem partnerships, and integration of sustainability and social responsibility into business practices. These elements present opportunities for financial institutions to differentiate themselves, foster trust and loyalty among stakeholders, and contribute to broader societal good. Ultimately, the ability to strike a delicate balance between short-term performance and long-term sustainability is critical in ensuring the industry’s continued relevance and success.\n\nBased on the findings and conclusions drawn from this study, several recommendations can be made to guide financial institutions in navigating the complex landscape and capitalizing on emerging opportunities. Financial institutions must cultivate organizational cultures that prioritize agility, flexibility, and willingness to adapt to rapidly changing market conditions. This may involve streamlining decision-making processes, fostering a culture of continuous learning and innovation, and empowering employees to take calculated risks and drive positive change.\n\nAttracting and retaining top talent is a strategic priority for financial institutions. This requires offering competitive compensation packages, providing opportunities for professional growth and development, and fostering an inclusive and supportive work environment that values diversity and encourages entrepreneurial thinking. Financial institutions should invest in robust data analytics capabilities and leverage data-driven insights to inform decision-making processes, understand customer behavior, identify risks and opportunities, and gain a competitive edge in the market. However, this must be balanced by a strong commitment to data privacy and ethical data management practices.\n\nFinancial institutions should actively explore and embrace emerging technologies such as artificial intelligence, blockchain, and cloud computing to streamline operations, enhance customer experiences, and drive innovation. Partnerships with fintech companies and technology providers can facilitate this process and provide access to innovative solutions.\n\nIt is imperative to integrate sustainable practices and social responsibility into business operations. Financial institutions should align their activities with environmental, social, and governance (ESG) principles; contribute to the broader societal good; and demonstrate a commitment to ethical and responsible business practices.\n\nFinancial institutions should actively seek strategic partnerships and collaborations with fintech companies, technology providers, academic institutions, and competitors. These ecosystem partnerships can facilitate knowledge sharing, access new technologies and talent pools, and drive innovation through a combination of complementary strengths and expertise.\n\nFinancial institutions must stay abreast of regulatory changes and actively engage with policymakers and regulatory bodies. This engagement can help shape the regulatory landscape, ensure compliance, and contribute to developing policies that support innovation while maintaining financial stability and consumer protection.\n\nThis study followed ethical research protocols. The work has been authorised by the University Research Ethics Committee (REC-270710-028-RA Level 01) on 21 April 2022. The participants were given an written informed consent form that explained the objective of the study, the voluntary nature of their participation, and the steps taken to protect the confidentiality and anonymity of their responses. Upon agreement, they signed the consent form (written). The researchers took measures to guarantee the secure storage of the acquired data, and any potentially identifiable information was eliminated or made anonymous to safeguard the privacy of the participants (Braun, Clarke, Boulton, Davey & McEvoy, 2020).\n\n\nAuthors contribution\n\nPC-study conceptualisation, methodology, data analysis, write-up; HM -methodology, data collection, data analysis, write-up; IU-supervision, proofreading and editing, Ethics Approval\n\n\nData sharing statement\n\nData can be accessed from the authors by sending an email (P.Cheteni at 200909553@ufh.ac.za) stating the reason why they need the data. Upon receipt of the email, the data will be released if the Protection of Personal Information Act, 2013 requirements as stipulated in South African law are satisfied.\n\nCHETENI, PRIVILEDGE (2024). Regulatory guidelines. figshare. Dataset. https://doi.org/10.6084/m9.figshare.26926987.v1",
"appendix": "References\n\nAromolaran O, Ngepah N, Saba CS: Macroeconomic determinants of poverty in South Africa: The role of investments in artificial intelligence. Access Journal. 2024; 5(2): 288–305. Publisher Full Text\n\nBraun V, Clarke V, Boulton E, et al.: The online survey as a qualitative research tool. International Journal of Social Research Methodology. 2020; 24(6): 641–654. Publisher Full Text\n\nBraun V, Clarke V: Toward good practice in thematic analysis: Avoiding common problems and be(com)ing a knowing researcher. International Journal of Transgender Health. 2022; 24(1): 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrown L, Rogers T: Qualitative and quantitative research methods for social sciences. Cambridge University Press; 2020.\n\nCloete F: Governing artificial intelligence (AI) and other technologies in the digital era. Administratio Publica. 2024; 32(1): 1–30.\n\nCheteni P: Regulatory guidelines. Dataset. figshare. 2024. Publisher Full Text\n\nCrabtree BF, Miller WL: Doing qualitative research. Sage Publications; 2023.\n\nDzingirai M: Effects of artificial intelligence on money laundering in Southern Africa. ICABR Conference. Cham: Springer Nature Switzerland; 2023, June; pp. 483–500.\n\nEkinci R: The impact of digitalization on financial sector performance. The Impact of Artificial Intelligence on Governance, Economics and Finance. 2021; I: 99–119. Publisher Full Text\n\nGarcia MB: Kinder Learns: An Educational Visual Novel Game as Knowledge Enhancement Tool for Early Childhood Education. The International Journal of Technologies in Learning. 2020; 27(1): 13–34. Publisher Full Text\n\nGarcia MB: Factors Affecting Adoption Intention of Productivity Software Applications Among Teachers: A Structural Equation Modeling Investigation. International Journal of Human-Computer Interaction. 2023; 40(10): 2546–2559. Publisher Full Text\n\nGigante G, Zago A: DARQ technologies in the financial sector: Artificial intelligence applications in personalized banking. Qualitative Research in Financial Markets. 2023; 15(1): 29–57. Publisher Full Text\n\nGiwa F, Ngepah N: Artificial intelligence and skilled employment in South Africa: Exploring key variables. Research in Globalization. 2024; 8: 100231. Publisher Full Text\n\nIrfan M, Elmogy M, El-Sappagh S: The impact of AI innovation on financial sectors in the era of industry 5.0. IGI Global; 2023.\n\nKuiper O, van den Berg M , van der Burgt J , et al.: Exploring explainable AI in the financial sector: Perspectives of banks and supervisory authorities. Artificial Intelligence and Machine Learning: 33rd Benelux Conference on Artificial Intelligence, BNAIC/Benelearn 2021, Esch-sur-Alzette, Luxembourg, November 10–12, 2021, Revised Selected Papers 33. Springer International Publishing; 2022; pp. 105–119.\n\nMangena A, Sithole P: The impact of robo-advisors on decision support management in a South African financial sector. EPiC Series in Education Science. 2024; 6: 179–188.\n\nMaple C, Szpruch L, Epiphaniou G, et al.: The AI revolution: Opportunities and challenges for the finance sector. arXiv preprint arXiv:2308.16538. 2023.\n\nMazzini G, Bagni F: Considerations on the regulation of AI systems in the financial sector by the AI Act. Frontiers in Artificial Intelligence. 2023; 6: 1277544. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMhlanga D: FinTech and artificial intelligence for sustainable development: The role of smart technologies in achieving development goals. FinTech and Artificial Intelligence for Sustainable Development: The Role of Smart Technologies in Achieving Development Goals. Cham: Springer Nature Switzerland; 2023; pp. 3–13.\n\nMishra S: Exploring the impact of AI-based cybersecurity financial sector management. Applied Sciences. 2023; 13(10): 5875. Publisher Full Text\n\nNowakowski M, Waliszewski K: Ethics of artificial intelligence in the financial sector. Przegląd Ustawodawstwa Gospodarczego. 2022; 2022: 2–9. Publisher Full Text\n\nNyugha PG: The importance of artificial intelligence to Africa’s development process: Prospects and challenges. PriMera Scientific Engineering. 2024; 4: 20–30.\n\nQwabaza A: The adoption of artificial intelligence in financial services in South Africa.2020.\n\nRabbani MR, Lutfi A, Ashraf MA, et al.: Role of artificial intelligence in moderating the innovative financial process of the banking sector: a research based on structural equation modeling. Frontiers in Environmental Science. 2023; 10: 978691. Publisher Full Text\n\nSony M, Naik S: Critical factors for the successful implementation of Industry4.0: a review and future research direction.Production Planning & Control.2020; 31(10): 799-815.\n\nVon Bertalanffy L: The History and Status of GST. Academy of Management Journal. 1972; 15: 407–426. Publisher Full Text\n\nWhitchurch GG, Constantine LL: Systems theory. Sourcebook of family theories and methods: A contextual approach. Boston, MA: Springer US; 1993; pp. 325–355."
}
|
[
{
"id": "348666",
"date": "09 Jan 2025",
"name": "Shoaib Khan",
"expertise": [
"Reviewer Expertise Capital structure",
"corporate finance",
"Islamic finance",
"Fintech"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the current form the paper has a enough material and potential but it requires a explicit reorganization and clarification in the following aspect.\nThe introduction is built on some sound arguments and the state of AI and its role in fintech industry. But the research fails to highlight an explicit research gap and based on this gap authors need to highlight the objectives and significance of the current study. The authors highlight the benefits and challenges related to AI in fintech. They should do a comparison of the role of AI in fintech in the context of SA and global perspective.\nThe study should highlight what is state / role of AI in global fintech industry and what is missing in South African context. In the similar context they should highlight the significance of this study, how it will contribute or beneficial for the enhancement of role of AI in fintech industry of South Africa.\nThere are a lot of repetitions related to the role AI in the introduction section and in section 2. To avoid redundancy, explain the terms and terminologies and their role in specific section preferably in section 2. E.g. check the 2nd paragraph of the introduction and 2nd and 3rd paragraphs of section 2 related to fraud detection. Other considerations are related to the use of AI for customer services.\nThe section 2 provides the review of both theoretical and empirical literature, in my opinion presentation could be improved, firstly reviewing the state of AI role in fintech industry of South Africa, followed by the system theory background and explanation, then review the relevant empirical literature.\nIn section 4.1.1 the participants highlighted an important concern related to the fintech i.e. regulatory landscape. This part highlights 3 important points related to the regulation issues faced by practitioners in the financial sector. But nothing related to the regulation has been highlighted in introduction or literature review. Most importantly authors fails to highlight this significant findings in their abstract and conclusion section. As a major finding of the study is related to the regulation side, therefore it is suggested to incorporate the regulation related literature in introduction and literature review section. Better to add the review of state of regulatory sandboxes, a unique regulatory environment for fintech startups in the context of South Africa.\nConclusion is not completely aligned with the introduction of the study. Also in the introduction and section2 authors mentioned about the financial inclusion, but nothing is related to financial inclusion is discussed in results or inferred in conclusion of the study.\nSuggested studies to review /citation : Refer 1 and 2\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1455
|
https://f1000research.com/articles/12-839/v1
|
17 Jul 23
|
{
"type": "Research Article",
"title": "Obstacles for self-management practices among diabetes patients: A facility-based study from Coastal South India.",
"authors": [
"Rekha T",
"Murali Mohan R",
"Nithin Kumar",
"Kausthubh Hegde",
"Bhaskaran Unnikrishnan",
"Prasanna Mithra",
"Ramesh Holla",
"Balanarayana Suma",
"Aadithya M Rao",
"Patil Nikitha",
"Aysha Roushida Sahama M",
"Rekha T",
"Murali Mohan R",
"Kausthubh Hegde",
"Bhaskaran Unnikrishnan",
"Prasanna Mithra",
"Ramesh Holla",
"Balanarayana Suma",
"Aadithya M Rao",
"Patil Nikitha",
"Aysha Roushida Sahama M"
],
"abstract": "Background The purpose of the study was to assess the obstacles faced by diabetes patients in their self-care and determine the factors associated with these obstacles. The management of diabetes mellitus (DM) extends beyond the clinician’s efforts, with the responsibility of the care also being shared by the patient to achieve better treatment outcomes and prevent complications. Self-care management is the most important part of DM treatment, which includes diet, regular exercise, blood glucose monitoring, medication and foot care.\n\nMethods A facility-based cross-sectional study was conducted among 107 type 2 DM patients aged >18 years using the Diabetes Obstacles Questionnaire-30. Patients scoring a mean response score >3 were considered to have an obstacle. We included age, gender, socioeconomic status (SES), duration of DM and blood glucose levels as factors for regression analysis and a P value <0.05 was considered to be statistically significant.\n\nResults A large majority (64.5%, n = 69) of our participants were aged above 55 years and belonged to lower socio-economic status (65.4%, n = 70). Family history of DM was present in 41% (n=44) of the participants. The median duration of DM among the participant was 10 (4 – 7) years.\n\nIn our study, the participants faced obstacles for two items in the domains: Support from Friends & Family (mean score: 3.73) and Knowledge of the Disease (mean score: 3.58). A multinominal regression analysis revealed SES was predictive of participants who could not understand information from literature with a P. value of 0.002 (OR: 3.65, CI: 1.60-8.338). Conclusion The two major obstacles to self-management practices that were identified were in the domains of Support from Friends and Family, and Knowledge of the Disease. Socioeconomic status was identified to be a predictive factor associated with the participants who are not able to understand information from the literature.",
"keywords": [
"Type 2 Diabetes mellitus",
"Cross-sectional study",
"Blood glucose self-monitoring",
"Socioeconomic status",
"Diabetes Obstacles Questionnaire-30"
],
"content": "Introduction\n\nDiabetes mellitus (DM) is a complex, chronic metabolic illness characterized by continuously elevated blood glucose levels which if not controlled will lead to complications related to the eyes, nerves, kidneys, and cardiovascular system, ultimately resulting in death.1 The World Health Organisation (WHO) has estimated that DM was responsible for over 1.5 million deaths in 2019, with 48% of the deaths occurring before 70 years of age.2 Affecting over 537 million people worldwide, the prevalence of DM has been rising over the past 3 decades.3 The rise in prevalence is predominantly reported in low- and middle-income countries, where deaths due to DM have increased by 13% over the past 20 years.1,3,4\n\nAccounting for 17% of the total diabetes population, India is often referred to as the ‘Diabetes capital’ of the world.5 India has an estimated 77 million people living with diabetes.\n\nAccording to the International Diabetes Federation (IDF), India ranks among the top three countries with the highest populations of people with diabetes, along with China, and the USA.6\n\nThe situation is made worse by the fact that 25 million people are in the stage of prediabetes, and are at higher risk of developing overt diabetes if their blood glucose is not controlled. The National Noncommunicable Disease Monitoring Survey (NNMS) carried out among adults aged between 18-69 years reported a 9.3% and 24.5% prevalence of DM and impaired fasting blood glucose (IFG) respectively.7 Also, 50% of the population in India is unaware of their diabetes status. A multi-centric study conducted in 2017 reported that 47% of DM cases remain undiagnosed in India, emphasizing the fact that awareness regarding the disease remains poor in the population.8 These undiagnosed cases of DM will end up with complications and burden the health system at various levels of care.\n\nThe complications arising from untreated or poorly treated DM are similar for both type 1 and type 2 DM, and make up a large portion of the morbidity and mortality associated with the disease. Diabetes also leads to significant financial implications, with the global economic burden estimated around US $1.31 trillion.9 Effective control and management of diabetes can prevent or delay the progression of the complications and can reduce the morbidity, mortality and the costs associated with this condition.10\n\nTreatment of diabetes is multifactorial, with multiple approaches working synergistically to control hyperglycaemia in the body. Weight loss and intensive lifestyle modifications are initial modalities of treatment, along with pharmacologic methods including drugs of various categories, like metformin, sulfonylureas, glinides, DPP-4 Inhibitors, SGLT-2 inhibitors among others.11\n\nIn addition to the various modalities of treatment available, self-management plays a pivotal role in the management of DM and prevention of its complications. Self-management is the regular activities the patients with DM do to control or lessen the effects on their physical health status.12 Self-care in DM is defined as an evolutionary process of knowledge or awareness development by learning to deal with the complexities of DM in a social context.13\n\nPractices focusing on self-care in diabetes include regular monitoring of blood glucose levels, regular physical activity, healthy eating, foot care, and compliance to medication should be given utmost importance.13 Relationships with medical professionals, support from friends and family, knowledge of the disease, and uncertainty about consultation are other important factors that can influence diabetes self-care.10\n\nSelf-monitoring of glucose levels provides a quick and easy way for a patient to identify periods of hyperglycaemia and undergo interventions as necessary. It can be used to promote modifications in treatment by a healthcare practitioners and is the most beneficial for those patients with suboptimal control over their glucose levels.14,15\n\nDiet control is one of the most significant factors that can be used to determine the level of self-care established.13 Weight loss is a cornerstone of the dietary recommendations of the American Diabetes Association, which recommends a lowered caloric intake to successfully reduce obesity and induce weight loss.16 Physical activity and exercise improves the physical and psychological health of the patient and also acts as an adjunct to the weight loss regimen.\n\nFoot care covers a variety of interventions such as foot temperature measurement, use of therapeutic footwear, patient education, inspection and assessment by professionals, with varying impacts.17 Proper foot care practices can lead to reduced development of complications like ulcers and amputations.18\n\nAdherence to the treatment is also critical as missed dosage of the prescribed drugs can lead to elevated glucose levels and development of the complications. It is important to consider perspectives of both the patient and provider perspectives when exploring self-care barriers. Improved self-care behaviour adherence has been linked to increased patient involvement in treatment decisions and satisfaction with provider communication.19 Patient’s knowledge about the disease, his attitude, and perception towards lifestyle modifications and various other aspects of diabetes self-care including treatment adherence and advice is considered to be important drivers for the prevention and control of diabetes.13 Clinicians may further influence the patient’s knowledge and attitude may further be influenced by the clinicians by using effective communication techniques and by having a healthcare system that is well-integrated.20\n\nAlthough self-care practices play crucial part in the control of DM, the patients find this complex process quite difficult to achieve on a day-to-day basis and face several barriers as they navigate through this approach.\n\nSeveral factors affect a patient’s ability to monitor blood glucose levels on a day-to-day basis. The studies from other countries have reported obstacles arising from poor communication between the medical practitioner and patients, to limited access to facilities and equipment.21 Another common factor that results in poor management of DM is the inadequate knowledge about the disease or its management either due to ignorance or scarcity of trustworthy sources that provide information regarding the disease.\n\nIn developing counties, financial difficulties majorly affect self-care and monitoring. Poor moral support from the family members or the lack of desire to impact a change on patients’ lifestyle also affects their self-care. To prevent the spread of COVID-19, countries resorted to frequent lockdown. This in turn, resulted in decreased access to outpatient care for regular check-ups. Isolation and stress also resulted in mental health issues, and this in turn also acted as barrier to self-management of DM.22\n\nUnderstanding diabetes and its necessity of long-term management requires self-motivation and support from loved ones. As this disease has no cure and can only be controlled in the long run, it becomes a challenging issue for doctors, community workers and patients to effectively manage the same.\n\nEffective self-management has extended psychological benefits, with decreased anxiety and depression reported among adherent patients.23 Appropriate self-management of diabetes can improve the quality of life, reduce healthcare expenses, and decrease the rate of complications.\n\nSelf-management thus plays a crucial part in the control of diabetes and the benefits it provides are immense. It is prudent to identify the barriers and obstacles that may decrease the utilisation of these practices.\n\nUnderstanding and identifying these challenges at the early stage of treatment is very important to achieve optimal blood glucose control and prevent complications. There is a paucity of literature regarding obstacles to diabetes self-care practices in India. With this background, a cross-sectional study was carried out to identify the obstacles to self-care among type 2 DM patients and the factors associated with the obstacles.\n\n\nMethods\n\nMangalore is a major port city in the district of Dakshina Kannada and is one among the largest city in the southern State of Karnataka, with a population of over 6 lakhs.24 With an average literacy rate of 93.7%24 which is higher than the national figure of 85%, the city is considered to be one among the educational hub in South India. It also serves as a major economic and health care centre with a health care index of 62.25\n\nDakshina Kannada is one among the high burden districts for diabetes with a prevalence of 14.8% and 15.4% among men and women respectively.26\n\nThis facility based cross-sectional study was carried out in the hospitals affiliated to Kasturba Medical College, Mangalore.\n\nIn this cross-sectional study, 107 patients with type 2 DM attending the medicine out-patient department in the hospitals affiliated to Kasturba Medical College, Mangalore were assessed regarding the obstacles for practicing diabetes self-care. All the participants were aged 18 years and above, and were diagnosed with DM for at least a year The study was conducted in the months of November and December, 2019.\n\nThe sample size of 107 was calculated based on the assumption that 50% of the DM patients face obstacles when practicing self-care, with an absolute precision of 10%, 95% confidence interval and adding a 10% non-response error. Gender of the participants was documented based on self-report. Gender difference in seeking care was not taken into consideration for the design of the study and reporting of the results, since it was a facility based study and patients were already seeking health care, we assumed that the barriers faced by the patients of either gender would be similar.\n\nThe participants were briefed about the purpose and objectives of the study. Written informed consent was obtained from the willing participants, following which the participants were taken to a separate room to ensure privacy, and face-to-face interviews were conducted by one of the authors (interviewer) who were familiarised with the contents of the semi-structured questionnaire, to avoid any bias in interview. The interviews were conducted in the language the respondents were comfortable with and the responses were recorded in a printed questionnaire by the interviewer at the time of interview. The duration of the interview was for 15-20 minutes on average.\n\nThe data was collected using a semi-structured questionnaire prepared after extensive review of literature. The questionnaire consisted of the following sections:\n\nSection A: Socio-demographic information of the study participants\n\nSection B: Details regarding the diabetes and self-care practices followed by the participants\n\nSection C: Diabetes Obstacles Questionnaire-30 (DOQ-30)10\n\nSection D: Clinical examination and lab investigations\n\nThe Diabetes Obstacle Questionnaire-30 is a validated instrument developed by Pilv L, et al.10 and consists of 30 items which gives a measure of Diabetes Related Quality of Life in nine subscales. The nine subscales include Relationship with medical professionals, Support from friends and family, Knowledge of the disease, Lifestyle changes, Exercise, Self-monitoring, Uncertainty about a consultation, Medication and Insulin-use among others. Each sub-scale comprises of 2 to 4 items which were assessed using a five-point Likert-scale (i.e., 5-Strongly Agree, 4-Agree, 3-Neutral, 2-Disagree and 1-Strongly Disagree).\n\nThe questionnaire was translated to Kannada, a local language, and was pretested and content validated for the language. The socioeconomic status of the participants was assessed using Modified Kuppuswamy’s Scale.27\n\nThe study protocol was approved by the Institutional Ethics Committee (IEC) of Kasturba Medical College, Mangalore (IEC number: IECKMCMLR/022/2018).\n\nPermission was obtained from the Medical Superintendent of KMC Hospital, Attavar, Mangalore, and District Medical Officer of Government Wenlock Hospital, Mangalore for conducting the study among the patients.\n\nThe collected data was entered in and analysed using IBM SPSS (Statistical Package for Social Sciences) Statistics version 25.0 for Windows (Armonk, NY: IBM Corp). The results were expressed using mean (standard error of mean), median (inter-quartile range) and proportions.\n\nFor the purpose of analysis and ease of interpretation, strongly disagree/disagree and strongly agree/agree were stratified into disagree and agree, respectively.\n\nThe items in the domains of DOQ-30 were considered an obstacle if the mean response score was 3 or more.\n\nFor the items which were identified to be an obstacle, multinomial logistic regression (MLR) analysis was applied taking neutral as reference modality to find out the factors responsible for the respective obstacle. Regression analysis with age, socioeconomic status (SES), duration of DM and blood glucose level as possible factors was done to find any association. Odds ratio and corresponding confidence interval were reported and P < 0.05 was considered as statistically significant association. The missing data, if any, were not considered for the analysis by deleting the variable response listwise.\n\n\nResults\n\nA total of 107 type 2 DM patients were included in the study. A large majority (64.5%, n = 69) of our participants were aged above 55 years, with the mean age of 60.3 (±10.9) years. A higher proportion (72%, n = 77) of the participants were males and belonged to lower socio-economic status (65.4%, n = 70). Family history of DM was present in 41% (n=44) of the participants.\n\nThe median duration of DM among the participant was 10 (4–7) years. About 58% (n = 62) of the participants had at least one comorbidity, with hypertension being the most common (82.2%, n = 51). The general information of the study participants is given in Table 1. The full dataset can be found under Underlying data.46\n\n* Modified Kuppuswamy scale, 2017.\n\n** Hypertension – 51 (47.6%).\n\nThe obstacles for diabetes self-care as assessed using DOQ-30 is depicted in Table 2. The mean response score for most of the items under various domains was less than 3.\n\nHowever, in one item each from the domains of Support from Friends and Family, and Knowledge of the disease, the participants scored more than the average cut-off of 3, suggesting an obstacle.\n\nThe mean response score for item, ‘I would manage my diabetes much better if I had encouragement socially’ (item one) under the domain, Support from Friends and Family, was 3.73 (0.12 SEM) with 79 (73.8%) participants agreeing that social support is important for diabetes control. The mean of response to the item, ‘I have difficulty understanding information from literature’ (item two) under the domain, Knowledge of the Disease was 3.58 (0.09 SEM) with 66 (61.7%) participants agreeing that they were unable to understand the information related to diabetes from the literature.\n\nMultinomial logistic regression (MLR) was applied on the two items identified to be obstacles for self-care to find out the significant factors associated with them.\n\nAbout 74% (n = 79) of participants stated that item one was an obstacle for self-care practice, while 7.47% (n = 8) of them were neutral about their response to this statement. MLR analysis with neutral as the reference category revealed no predictive factors for this obstacle.\n\nItem two was an obstacle for 61.68% (n = 66) of the participants, while 23.3% (n = 25) were neutral about their response. MLR analysis revealed socioeconomic status is a strong predictor of this obstacle with P. value of 0.002 (odds ratio: 3.65 and confidence interval: 1.60-8.33). The other factors were statistically insignificant. This data is summarised in Table 3. The data of some of the examination findings (height, weight, BMI) and lab values (HbA1c and blood cholesterol levels) were missing. Those parameters were not considered for analysis in our study.\n\n\nDiscussion\n\nIn this facility based cross-sectional study, 107 type 2 diabetes patients were assessed about the obstacles for diabetes self-care practices using the Diabetes Obstacles Questionnaire-30 (DOQ-30).10 Very few studies have been conducted to understand the barriers for self-management practices and to determine possible predictive factors for these obstacles among the DM patients.\n\nAmong the 30 items across 9 domains of self-care, only 2 items were considered as obstacles by the participants in our study. The lack of social encouragement for better management of disease and difficulty in understanding the literature about the disease were agreed upon by the participants to be a challenge for practicing self-care.\n\nLack of social support as a barrier for diabetes self-management was reported by a multi-national study, where effective social support system with constant motivation and encouragement from friends and family members were identified as enablers for self-management.28 The importance of social support in diabetes has been documented in multiple studies, where strong social support leads to a better degree of self-management and overall positive outcomes.29,30 A systematic review and meta-analysis conducted by Youngshin et al.31 found social support to be significantly associated with self–management, with the strongest effect on regular glucose monitoring. On the contrary, lack of support and isolation, for example a patient living alone, is associated with poor self-management, including a reluctance to use insulin, medicines, and irregular testing of blood glucose levels. They are also more likely to not follow any diet plan to avoid the stigma and embarrassment associated with diabetes.32 A lack of support from family and friends can directly lead to poorer psychological wellbeing, improper or less than adequate self-management, and ultimately lead to suboptimal glycaemic control and poor outcomes for the patient.\n\nDifficulty in understanding diabetes related literature was also identified as an obstacle in our study. Poor level of knowledge among patients with chronic diseases, especially diabetes is well documented, with low level of health literacy being reported between 15 to 40% of the population.33 Various studies from USA and Japan have documented that low health literacy is associated with poor diabetes knowledge, which can in turn affect the practice of diabetes self-care.34–36\n\nThe role of education in diabetes self-care is well documented with various studies reporting a correlation between lower educational status of the patient and poor self-management practices.37–39 A study by Aziz, et al.,18 reported a correlation between education of the patient and foot care practices, along with a decreased rate of amputations associated with diabetes. A similar study conducted by Chai et al.40 showed a significantly increased psychological health and decreased glucose levels after six months following self-management education. An integrative review by Olesen et al.41 found a patient centred approach to diabetes self-management education to have a noticeable impact in improving the self-management, leading to better haemoglobin A1c levels, as well as the quality of life of the patients.\n\nSeveral studies have reported an adequate control of blood glucose levels and improvement in morbidity and mortality if the patients follow self-management behaviours such as blood glucose monitoring, nutrition, exercise, medication, and foot care.18,37–41 Diabetes education is thus very important and should be an integral part of every diabetes control program.\n\nSocial support and education have been identified to work synergistically to bring about improvement in clinical outcomes in a diabetes patient.12\n\nThe other primary objective of our study was to identify the factors that may be predictive of the obstacles for the self-care management among diabetes patients. We considered two statements from DOQ-30: ‘I would manage my diabetes much better if I had encouragement socially’ and ‘I have difficulty understanding information from literature’, which were reported to be the obstacles faced by the study participants and we tried to predict the factors for these obstacles.\n\nMLR analysis revealed socioeconomic status (OR – 3.65, CI – 1.60-8.33 and P – 0.002) to be significantly associated with participants not being able to understand the diabetes related literature. No factors were found to be significantly associated with lack of social support for diabetes management among the participants.\n\nDiabetes self-care is a complex process which involves dietary modifications, regular exercising, regular blood glucose monitoring and compliance to treatment, all of which work synergistically to achieve an optimum blood glucose level. Older diabetes patients have a unique set of problems which make practicing diabetes self-care challenging. Decreased physical and cognitive abilities, presence of comorbidities, and complications, polypharmacy, absence of support system, change in dietary habits, and depression associated with chronic diseases will hamper the diabetes self-care behaviour.42 Increased age could possibly be a predictor for hesitancy and reluctance in obtaining information and a difficulty in comprehension.\n\nSocio-economic status is a multidimensional factor, which is a combination of educational, economic and occupational status. It is linked with Social Determinants of Health (SDOH) which includes accessibility to quality health care, good nutrition, transportation, housing, and social engagement, all of which can affect disease management. Low SES indicates a lower level of education. In our study, SES was found to be a predictive factor for patients not being able to understand information regarding diabetes from literature. All levels of SES have been consistently reported to be a strong predictor for disease onset and progression for many chronic diseases, including diabetes.43\n\nPatients belonging to lower SES are more likely to develop diabetes, poor self-care management, experience complication, than those belonging to higher SES.44,45\n\nThe obstacles of diabetes self-care faced by the participants in our study were mainly due to their poor education and lower economic status. Based on the results of the DOQ-30, the majority of the patients did not have any problem following a diet or an exercise pattern as they felt that these lifestyle modifications were necessary to lead a longer and better life. The healthy relationship between the participants and healthcare providers likely ensured better information exchange to manage their diabetes in an efficient manner.\n\nThe results of this facility-based investigation cannot be generalised to the broader population. The domain of self-monitoring was difficult to assess since the majority of the participants in our study belonged to low SES and did not have provision for self-monitoring of blood glucose. Also, the domain of Insulin use was also difficult to assess since the majority of our study participants were not prescribed insulin.\n\n\nConclusions and recommendations\n\nIn our study, the two major obstacles for self-management practices that were identified were in the domains of Support from Friends and Family, and Knowledge of the Disease. Socioeconomic status was identified to be a predictive factor associated with the participants who are not able to understand information from the literature. Self-management is an integral component of the treatment plan of diabetes and can lead to more positive outcomes. Targeting these barriers as identified in our study could improve self-management. Having a strong social support network could be advised and encouraged. An increased focus on patient education and awareness both in primary care as well as awareness programs could lead to decreased rate of complications, and an increased quality of life for patients moving forward.",
"appendix": "Data availability\n\nOSF: “Obstacles for Self-Management Practices Among Diabetes Patients - A Facility-based Study from Coastal South India.” https://doi.org/10.17605/OSF.IO/9EN45. 46\n\nThis project contains the following underlying data:\n\n- Final.xlsx [raw data]\n\nThis project contains the following extended data:\n\n- Key.xlsx [This Microsoft Excel Spreadsheet has the key to interpret the data in the file named Final.xlsx]\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWe are thankful to all of our study participants for their cooperation in our research study. We thank the Department of Community Medicine, Kasturba Medical College, Mangalore, and the Manipal Academy of Higher Education (MAHE), Manipal for their support for this research and its publication.\n\nWe acknowledge the authors Pilv L, et al., of the article entitled ‘Development and Validation of the short version of the diabetes obstacles questionnaire (DOQ-30) in six European countries’ published in 2015 at European Journal of General Practice for granting permission to use the Diabetes Obstacles Questionnaire - 30 in our study. The questionnaire is copyright © 2016 of WONCA Europe (the European Society of General Practice/Family Medicine), and reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com on behalf of 2016 WONCA Europe (the European Society of General Practice/Family Medicine).\n\n\nReferences\n\nWorld Health Organization: Diabetes.2022. Accessed March 11, 2023. Reference Source\n\nWorld Health Organization: Diabetes.2022. Accessed March 11, 2023. 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Publisher Full Text\n\nAmerican Association of Clinical Endocrinologists: The American Association of Clinical Endocrinologists Medical Guidelines for the Management of Diabetes Mellitus: the AACE system of intensive diabetes self-management--2000 update. Endocr. Pract. 2000; 6(1): 43–84.\n\nvan Netten JJ , Price PE, Lavery LA, et al.: Prevention of foot ulcers in the at-risk patient with diabetes: a systematic review. Diabetes Metab. Res. Rev. 2016; 32(Suppl 1): 84–98. PubMed Abstract | Publisher Full Text\n\nNather A, Cao S, Chen JLW, et al.: Prevention of diabetic foot complications. Singap. Med. J. 2018; 59(6): 291–294. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMogre V, Johnson NA, Tzelepis F, et al.: Barriers to diabetic self-care: A qualitative study of patients’ and healthcare providers’ perspectives. J. Clin. Nurs. 2019; 28(11-12): 2296–2308. PubMed Abstract | Publisher Full Text\n\nNam S, Chesla C, Stotts NA, et al.: Barriers to diabetes management: patient and provider factors. Diabetes Res. Clin. Pract. 2011; 93(1): 1–9. Publisher Full Text\n\nShi C, Zhu H, Liu J, et al.: Barriers to Self-Management of Type 2 Diabetes During COVID-19 Medical Isolation: A Qualitative Study. Diabetes Metab. Syndr. Obes. 2020; 13: 3713–3725. Published 2020 Oct 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMohseni M, Ahmadi S, Azami-Aghdash S, et al.: Challenges of routine diabetes care during COVID-19 era: A systematic search and narrative review. Prim. Care Diabetes. 2021; 15(6): 918–922. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVas A, Devi ES, Vidyasagar S, et al.: Effectiveness of self-management programmes in diabetes management: A systematic review. Int. J. Nurs. Pract. 2017; 23(5). Publisher Full Text\n\nDakshina Kannada District Population, Caste, Religion Data (Karnataka) - Census 2011. Accessed March, 15 2023. Reference Source\n\nNumbeo: Current Health Care Index. Accessed March, 15 2023. Reference Source\n\nDistrict Fact Sheet. Dakshina Kannada- Karnataka. National Family Health Survey 2019-20. Accessed March, 15 2023. Reference Source\n\nMajumder S: Socioeconomic status scales: Revised Kuppuswamy, BG Prasad, and Udai Pareekh’s scale updated for 2021. J. Family Med. Prim. Care. 2021; 10(11): 3964–3967. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdu MD, Malabu UH, Malau-Aduli AEO, et al.: Enablers and barriers to effective diabetes self-management: A multi-national investigation. PLoS One. 2019; 14(6): e0217771. Published 2019 Jun 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWiebe DJ, Berg CA, Mello D, et al.: Self- and Social-Regulation in Type 1 Diabetes Management During Late Adolescence and Emerging Adulthood. Curr. Diab. Rep. 2018; 18(5): 23. Published 2018 Mar 21. PubMed Abstract | Publisher Full Text\n\nAmpadu JV: The Role of Social Support in Diabetes Self-Management Activities Among African-Americans. J. Natl. Black Nurses Assoc. 2021; 32(1): 22–27. PubMed Abstract\n\nSong Y, Nam S, Park S, et al.: The Impact of Social Support on Self-care of Patients With Diabetes: What Is the Effect of Diabetes Type? Systematic Review and Meta-analysis. Diabetes Educ. 2017; 43(4): 396–412. PubMed Abstract | Publisher Full Text\n\nSchabert J, Browne JL, Mosely K, et al.: Social stigma in diabetes: a framework to understand a growing problem for an increasing epidemic. Patient. 2013; 6(1): 1–10. Publisher Full Text\n\nCavanaugh KL: Health literacy in diabetes care: explanation, evidence and equipment. Diabetes Manag (Lond). 2011; 1(2): 191–199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIshikawa H, Takeuchi T, Yano E: Measuring functional, communicative, and critical health literacy among diabetic patients. Diabetes Care. 2008; 31(5): 874–879. PubMed Abstract | Publisher Full Text\n\nOsborn CY, Bains SS, Egede LE: Health literacy, diabetes self-care, and glycemic control in adults with type 2 diabetes. Diabetes Technol. Ther. 2010; 12(11): 913–919. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilliams MV, Baker DW, Parker RM, et al.: Relationship of functional health literacy to patients’ knowledge of their chronic disease. A study of patients with hypertension and diabetes. Arch. Intern. Med. 1998; 158(2): 166–172. Publisher Full Text\n\nKumar L, Mohammadnezhad M: Perceptions of patients on factors affecting diabetes self-management among type 2 diabetes mellitus (T2DM) patients in Fiji: A qualitative study. Heliyon. 2022; 8(6): e09728. Published 2022 Jun 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMikhael EM, Hassali MA, Hussain SA, et al.: Self-management knowledge and practice of type 2 diabetes mellitus patients in Baghdad, Iraq: a qualitative study. Diabetes Metab. Syndr. Obes. 2018; 12: 1–17. Published 2018 Dec 17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBorba AKOT, Arruda IKG, Marques APO, et al.: Knowledge and attitude about diabetes self-care of older adults in primary health care. Conhecimento sobre o diabetes e atitude para o autocuidado de idosos na atenção primária à saúde. Cien. Saude Colet. 2019; 24(1): 125–136. PubMed Abstract | Publisher Full Text\n\nChai S, Yao B, Xu L, et al.: The effect of diabetes self-management education on psychological status and blood glucose in newly diagnosed patients with diabetes type 2. Patient Educ. Couns. 2018; 101(8): 1427–1432. PubMed Abstract | Publisher Full Text\n\nOlesen K, Folmann Hempler N, Drejer S, et al.: Impact of patient-centred diabetes self-management education targeting people with type 2 diabetes: an integrative review. Diabet. Med. 2020; 37(6): 909–923. PubMed Abstract | Publisher Full Text\n\nWeinger K, Beverly EA, Smaldone A: Diabetes self-care and the older adult. West. J. Nurs. Res. 2014; 36(9): 1272–1298. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdler NE, Newman K: Socioeconomic disparities in health: pathways and policies. Health Aff (Millwood). 2002; 21(2): 60–76. Publisher Full Text\n\nAgardh E, Allebeck P, Hallqvist J, et al.: Type 2 diabetes incidence and socio-economic position: a systematic review and meta-analysis. Int. J. Epidemiol. 2011; 40(3): 804–818. PubMed Abstract | Publisher Full Text\n\nBrown AF, Ettner SL, Piette J, et al.: Socioeconomic position and health among persons with diabetes mellitus: a conceptual framework and review of the literature. Epidemiol. Rev. 2004; 26: 63–77. PubMed Abstract | Publisher Full Text\n\nKumar N: Obstacles for Self-Management Practices Among Diabetes Patients - A Facility-based Study from Coastal South India.2023. Publisher Full Text"
}
|
[
{
"id": "273975",
"date": "26 Sep 2024",
"name": "Ganesh Kumar Saya",
"expertise": [
"Reviewer Expertise Maternal and Child health",
"disability"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an important public health issue due to the high problem burden of diabetes. However the following points may be clarified:\nSince this study is done in a tertiary care hospital, the original residential status of the participant details may be mentioned in methods section. Whether there are similar studies by using the same questionnaire? If so, it may be applied for minimal sample size calculation. Whether details of accepted standard self care practices may be elaborated in methods section as mentioned in section B of data collection? If self management practice also convey the same meaning, same words may be used.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12891",
"date": "02 Dec 2024",
"name": "Nithin Kumar",
"role": "Author Response",
"response": "Since this study is done in a tertiary care hospital, the original residential status of the participant details may be mentioned in methods section. Response: Thank you, sir, for the suggestion. The details have been incorporated in the manuscript. Whether there are similar studies by using the same questionnaire? If so, it may be applied for minimal sample size calculation. Response: During our review of literature, we couldn’t find any Indian studies where self-care practices was assessed using the Diabetes Obstacles Questionnaire-30 (DOQ-30). Few of the studies had used Summary of Diabetes Self-care Activities (SDSCA) scale. Hence we went by the assumption for sample size calculation. Whether details of accepted standard self-care practices may be elaborated in methods section as mentioned in section B of data collection? If self-management practice also conveys the same meaning, same words may be used Response: The participants were asked about diabetes self-care practices under the domains of diet, exercise, blood glucose monitoring, medication compliance, and foot care. They were also asked if they had any self-reported obstacles to following these practices during the preceding week of the study. Diabetes self-management and Diabetes self-care practices are the same."
}
]
}
] | 1
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https://f1000research.com/articles/12-839
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https://f1000research.com/articles/12-849/v1
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19 Jul 23
|
{
"type": "Research Article",
"title": "Development and acceptability of a cereal bar with Atta sexdens ant flour",
"authors": [
"Michelle Lozada-Urbano",
"Jessica Bendezú Ccanto",
"Julissa Condori Chura",
"Oriana Rivera-Lozada",
"Jaime A. Yañez",
"Jessica Bendezú Ccanto",
"Julissa Condori Chura",
"Oriana Rivera-Lozada",
"Jaime A. Yañez"
],
"abstract": "In Peru, insect consumption, as a nutritional complement or as the main source in the diet, is limited to the regions of our the central jungle where Atta sexdens ants are consumed. An energy bar based on Andean grains with Atta sexdens ant flour was formulated. The ants were obtained from the department of San Martin, district of Rioja, province of Rioja. Four different formulations were prepared with different Atta sexdens ant flour concentrations: 13%, 17%, 20%, and 23%. Moisture, total fat, ash, proteins, fiber, carbohydrates, instrumental texture, and organoleptic analysis (taste, texture, and color) were performed. The developed cereal energy bar presented a 10 g protein content in 100 g of the final product. Acceptability was evaluated in adolescents and young adult populations. The developed cereal bars presented a high protein content, adequate organoleptic properties and high acceptability.",
"keywords": [
"Entomophagy",
"energy bar",
"Atta sexdens",
"protein",
"ant",
"insect edible."
],
"content": "Introduction\n\nThe Food and Agriculture Organization of the United Nations (FAO) recommends the consumption of edible insects because It is a sustainable alternative that replaces animal meat, such as beef, poultry, and fish.1 In Africa, Latin America, and Asia, these insects are commonly used to feed their populations.2 In Mexico alone, 549 species of ants have been reported to be consumed by diverse ethnic groups of this country.3\n\nIt has been reported that in Thailand their diet has been diversified with the consumption of sago worms4 and Acheta domesticus grasshoppers.5 Similarly, ants and bees have been reported to be consumed in Cameroon.6 In Peru, the consumption of Suri, a species of Rhynchophorus palmarum worm, and ants known as Mamako or Siqui Sapa (Atta sp.) has been reported to be widely consumed because of their pleasant taste.7\n\nInsects have high nutritional value because of their high content of fats, proteins, vitamins, fiber and minerals, which is a great opportunity for the development of healthy foods.8 Mealworm has a high content of unsaturated omega-3 fatty acids and healthy fats in similar quantities than fish, and their content of protein, vitamin and micronutrients is similar to fish and meat.9 In addition, protein from insects has been reported to produce a lower impact in the environment than obtaining protein from cattle or poultry.2\n\nMany insect species are consumed alone or have been included in other preparations. In the Netherlands, pasta has been made with durum wheat with the addition of cricket powder.10 Cereal bars are In this study, an accessible and an easily consumed product by adolescents and children. Consuming them in the morning and mid-morning can be beneficial to humor and memory behavioral aspects.11 According to the Codex Alimentarius, a cereal bar is mainly prepared with one or more ground cereals.12 Sales of nutrition bars increased almost tenfold in the last decade, and may be a way to utilize processed insect flour,13 because of the easiness of consumption. To the best of our knowledge there are no studies that have included ant flour in cereal bars. Therefore, the objective of this study was to develop a cereal bar with Andean cereals and the addition of ant flour, evaluate its nutritional value, fracturability, compression. A microbiological analysis was performed, as well as acceptability in a population of adolescents and young people.\n\n\nMethods\n\nAtta sexdens ants have been taxonomically assessed based on their morphological characteristics.14 These ants are brown or dark brown in color and the adult ants present three pairs of spines of approximately 6 to 14 mm, build their nests in underground tunnels of up to eight meters deep and can cover an area of 50 to 100 m2, and cut pieces of leaves, which they transport to their nest following visible paths.15\n\nThe siqui sapa ants were brought from the department of San Martín, province and district of Rioja, and were obtained through a distributor. The ants were transported to Lima and delivered in vacuum packaging to maximize the conservation of the product.\n\nFor the preparation of ant flour, the ants were placed in an oven at 65°C for 220 minutes. Of a sample of 100 g, we obtained 72.1 g of our final product. This was taken to an electric grinder until the flour was obtained. To avoid lumps and large particles, the flour passed through a stainless-steel sieve to obtain a homogeneous product.\n\nThe ingredients used were expanded kiwicha (100 g: 24.6 g protein, 7 g carbohydrates) and quinoa (100 g, 8 g protein, 85 g carbohydrates), also called expanded cereals. The dried fruits used were pecans (100 g: 9.1 g protein, 73.8 g fat, 11.7 g carbohydrate), peanuts (100 g: 27.1 g protein, 51 g fat, 16 g carbohydrate), almonds (100 g: 23.4 g protein, 54.1 g fat, 14.3 g carbohydrate), raisins (100 g: 2.4 g protein, 63.8 g carbohydrates), and coconut (100 g: 12 g de protein, 23 g total fat, 26 g carbohydrates). Shredded coconut and unflavored gelatin were purchased from a supermarket in the city of Lima. The process began with the preparation of inverted sugar syrup at 60° Brix, H2O/Sugar (50%-50%), which was used to compact the energy bars.\n\nThe expanded quinoa, kiwicha, dried fruits and ant flour were mixed together with the inverted syrup and glucose. The product was compacted with the help of molds to obtain cylindrical shapes. Figure 1 shows the procedure for the cereal bar formulation.\n\nWe measured the nutritional composition (fat, moisture, protein, carbohydrates, ash) in the four types of energy bars with ant flour in different concentrations and in the control bar, determined by AOAC standard methods. Moisture was determined according to AOAC 925.09,16 fat according to AOAC 922.06,17 ash according to AOAC 923.03,18 protein according to AOAC 984.1319 using 6.25 as the nitrogen to protein conversion factor for all samples. Carbohydrates were calculated by subtracting the percentages of fat, moisture, protein, carbohydrates, and ash from 100%.20\n\nTwo sensory quality attributes of the energy bars were evaluated. The analysis was performed using the TVT 6700 texture analyzer - Perten Instruments and TexCalc software. Fracturability is defined as the force required to fracture the sample significantly.21 The three-point bending method was used with the following parameters: initial speed of 1 mm/s, speed of 0.5 mm/s during the test, 0.1961 N tensile strength, 40 mm distance between support points.22 For the initial speed of compression test we used 2 mm/s; speed during the test, 2 mm/s; recoil speed, 10 mm/s; tensile strength, 0.049 N. The values of the strength required (N) to compress the specimen to 20% of its original thickness were recorded.23\n\nThe detection method for Salmonella was ICMSF (International Commission Microbiological Specifications for Foods). For Escherichia coli the ICMSF for the determination of fecal coliform organisms was used.24 For yeast25 and mold26 count the ICMSF method was used through seeding plates. Mesophilic aerobic microorganisms were counted using the ICMSF methods.27\n\nThe study was conducted by two nutritionists. A total of 100 participants were recruited, including adolescents and young people from two secondary schools, who were chosen as a population that frequently consumes bars. They received an invitation via whatsApp to participate in this study. Few participants (n=13) were contacted by calling them on their cell phones by the nutritionist in charge of administering the taste test, defined as a preference test. The inclusion criteria were adolescents and young adults who agreed to try the energy bars.\n\nThe acceptability was determined using a hedonic test, in which the recruited population was not trained. The samples had different three-digit random codes for each type of bar, a bottle of water was previously given to each participant in order to drink after each test, and strict cleanliness conditions were maintained at all times.\n\nThe report of the hedonic test results was recorded in an Excel table, which was subsequently analyzed using the SPSS statistical package. The results of the physical organoleptic analysis, the proximate analysis, and the microbiological analysis were shown in tables, indicating frequencies and percentages. The data was expressed in percentages and the experimental data was analyzed using the Kruskal-Wallis test. Normality was previously measured with Kolmogorov-Smirnov. The IBM SPSS Statistics version 25 statistical package was used.\n\nAll participants signed the informed consent form, before participating, all participants were informed that the cereal bar was made with Andean cereals and ant flour. The study received the approval of the ethics committee Exp. N°054-2020 of the Universidad Norbert Wiener.\n\n\nResults\n\nThe composition of the four types of energy bars and the amount of ant flour are shown in Table 1. The data are expressed in 100 g of product.\n\nThe proximate analysis showed the increase in fat and proteins as the percentage of ant flour increases in the four different concentrations (Table 2).\n\nThe analysis of compressibility assessed hardness. The method fitted the consistency of the sample due to the fact that, in order to delimit the assays’ parameters, the greatest force exerted was within 20% of compression, and values between 80.5 N and 117.6 N were obtained (Table 3, Figure 2).\n\nFigure 2 shows the fracture curves of the treatments with 15%, 20%, 25% and 30% of ant meal T15, T20, T25 and T30 respectively. In general we can observe 3 axes that are force (N), time (s) and distance (mm). The arrow of the indicated point (Hardness) expresses the maximum force exerted to fracture the samples, for example in graph T15, the maximum force exerted to fracture the sample is observed 98.9 N, with a time of 2.9 s and a distance of 1.41 mm. Figure 3 shows the compressibility curves in the same way we can observe 3 axes that are force (N), time (s) and distance (mm), an arrow of the indicated point (Hardness) expresses the maximum force exerted to compress by 20% each of the bars, from which the parameters of distance and time used are obtained, all of these under the same initial conditions mentioned in the methodology of both tests. For example, in the T30 graph, it is observed that to compress the sample by 20%, a force of 118 N is required with a distance of 4 mm in 2.3 s.\n\nThe median age of the tasters was 20.5, with a range of 15 to 25 years old. The four types of bars with different concentrations of ant flour were evaluated. Taste, texture, and color were assessed, and they were expresses through a hedonic scale. The four types showed high acceptability, the percentage of the acceptability index was also high (Table 4).\n\n* According to Kruskall-Wallis, p-values >0.05; therefore, the level of taste, texture, and color is the same in each of the formulations.\n\nThe analyzed sample was T4 for being the one with the highest amount of protein. The obtained values were within the limits allowed according to 071-MINSA-DIGESA-V01 (the sanitary technical norm in Peru) (Table 5).28\n\n* Based on 071-MINSA-DIGESA-V01.28\n\n\nDiscussion\n\nThe four types of bars with different percentages of ant flour were assessed (F1: 13%; F2: 17%; F3: 20%; F4: 23%). We used cereal such as quinoa and kiwicha, dried fruit (chestnuts, nuts, peanuts, almonds, and raisins). The proximate analysis showed that fat and proteins increased as the amount of ant flour increased as well, in comparison with the control bar made without ant flour (F0). Compressibility values ranged from 80.5 N to 117.6 N, and fracturability ranged from 8.48 to 12.33. We did not find any differences among the cereal formulations. All of them showed an acceptability index higher than 95%.\n\nThe fat and proteins increase with the addition of the ant flour is noticeable. A study with ant meal from the Rioja area in Peru showed 35.40% fat, 35.5% protein, with a pepsin digestibility of 99.77%.29 It is known that the ants’ abdomen is fatty and that roasted ants are mixed with rice and cassava flour in Brazil and consumed regularly.30 The protein value of insects has a composition similar to vertebrates’ such as pork, chicken, and fish.31 Cephalotes ants have 42.59% protein, chicken 23%, and beef 20%. In addition, insects are high in sodium, potassium, zinc, magnesium, iron, copper, and calcium.14,32 Other cereal bars made with similar products provide a lower amount of protein per serving.\n\nIn our study we obtained compressibility values ranging from 98.9 N to 117.6 N, which were obtained in the sample with the highest amount of protein (10.5 g). Alvarez obtained values from 130 N to 167 N in his cricket flour bars’ formulation, which was higher compared to our results. Alvarez attributed the difference to the protein content of the flour studied. However, it was concluded that the trend does not show significant differences due to the variability of the bars’ pieces, in addition to the structure of the bar because of the random distribution of dried fruit fragments.33 A study with cereal bars with quinoa flakes reported values between 112 N and 216 N,18 in which the sample with the highest hardness (216 N) that did not have quinoa in its composition was rated in the sensory analysis with “I slightly dislike it” and was associated with the hardness of the product as one of its characteristics. Some products with high fiber content are denser and harder; this does not imply a lower acceptance of the product.22 but a bar easy to crumble and with excessively firmness would not be attractive to the consumer. At sensory level, this analysis correlates with the maximum force exerted between the molars of each panelist.34\n\nThe fracturability test imitate chewing with the incisors. One study compared instrumental sensory texture to the maximum force exerted when biting (shear force), that research concluded that a bar with a higher breaking force might be crumbly but a bar that is easy to crumble does not imply that it requires a higher breaking force.34 In our study, we observed a higher force required by the 25% and 30% treatments, and a lower force by the 15% and 20% treatments. The values obtained varied between 8.48 N to 12.33 N of compression. Marquez L obtained data between 23.9 to 33.8 N, which shows the wide range of firmness in these products when comparing this data with previous research.22 According to a study on the addition of chontaduro flour to cereal bars,35it is expected to observe different resistance characteristics given by the addition of different concentrations of the ingredients during the elaboration of the bars. Texture properties are linked to the composition of each ingredient in the product such as flour granulometry, structure, and nutritional value, which are manifested in the results obtained by the shear or compressive strength of the sample, which give a particular attribute to the product.\n\nThe four types of bars with different concentrations of ant flour were evaluated by 100 students. Taste, texture and color were evaluated and expressed by a hedonic scale. The acceptability index had values above 95 %. Although no other bars with Atta sexdens flour addition have been found to compare with, information has been collected from several cereal bars with different cereals in their composition. One study revealed that appearance is the limiting factor for consumer acceptability, essentially for cereal bars with dried fruits as ingredients.36 They found higher acceptability when the bars had medium sugar concentration and high dietary fiber and β-glucan content.37 In a cereal bar made with textured soy protein, wheat germ, and oats, enriched with ascorbic acid and α-tocopherol acetate. The formulation de Freitas evaluated was high in protein (15.31%), vitamin E (118.0 mg/100 g). The formulation with 1.1 g/100 g of ascorbic acid added obtained a higher significant sensory preference.38\n\nThe results in this study showed absence of Salmonella, the count of molds and yeasts was 1.0 × 101 CFU/g, 4.0 × 101 CFU/g for aerobic mesophiles, and for Escherichia coli the result was <3 NMP/g. In general, the results were favorable and within the allowed limits. The cereal bars have low water activity, comply with sanitary specifications, and can be stored for 60 days. The yeasts, Bacillus cereus and fecal coliforms’ microbiological validation, performed by Gutkoski was acceptable for the Brazilian standards.37\n\n\nConclusions\n\nThe energy bars with ant flour were successfully developed and the sensory result of taste, texture and color attributes showed great acceptance, and any of them can be used for industrial scaling, especially the formulation containing 23% of ant flour that reached a high amount of protein. This product can be a good source of protein, fats and minerals and an alternative for consumers in general. The microbiological results of the energy bars were within the allowed parameters, making this product safe and suitable for consumption.",
"appendix": "Data availability\n\nFigshare: Risk perception. DOI: 10.6084/m9.figshare.23157566\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nVan Huis A, Van Itterbeeck J, Klunder H, et al.: Edible insects: future prospects for food and feed security. Food and Agriculture Organization of the United Nations. 2022. Retrieved October 6. Reference Source\n\nRaheem D, Raposo A, Oluwole OB, et al.: Entomophagy: Nutritional, ecological, safety and legislation aspects. Food Research International. Elsevier Ltd.; 2019; 126. Publisher Full Text\n\nRamos-Elorduy J: Energy supplied by edible insects from Mexico and their nutritional and ecological importance. Ecol. Food Nutr. 2018; 47(3): 280–297. Publisher Full Text\n\nNirmala IR, Mph T, Mph S, et al.: Sago worms as a nutritious traditional and alternative food for rural children in Southeast Sulawesi, Indonesia. Asia Pac. J. Clin. Nutr. 2017; 26: 40–49. Publisher Full Text\n\nYen AL: What is traditional? J. Insects Food Feed. Wageningen Academic Publishers; 2016; 2(2): 67–68. Publisher Full Text\n\nTamesse JL, Kekeunou S, Tchatchouang LJ, et al.: Insects as food, traditional medicine and cultural rites in the west and south regions of Cameroon. J. Insects Food Feed. 2016; 2(3): 153–160. Publisher Full Text\n\nMedina Quispe LV, Malpartida Ticlavilca MS, Quiroz Casana AG: Entomofagia: una oportunidad de mercado favorable al medio ambiente. Empresa B “VALLE Y PAMPA” [Pontificia Universidad Católica del Perú]. Pontificia Universidad Católica del Perú; 2019. Reference Source\n\nEl Hajj R, Mhemdi H, Besombes C, et al.: Edible Insects’ Transformation for Feed and Food Uses: An Overview of Current Insights and Future Developments in the Field. Processes. 2022; 10: 5. Publisher Full Text\n\nFood and Argriculture Organization of the United Nations: Edible insects. Future prospects for food and feed security. Food and Agriculture Organization of the United Nations; 2013; 171.\n\nDuda A, Adamczak J, Chelminska P, et al.: Quality and nutritional/textural properties of durum wheat pasta enriched with cricket powder. Foods. 2019; 8(2). PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmith AP, Wilds A: Effects of cereal bars for breakfast and mid-morning snacks on mood and memory. Int. J. Food Sci. Nutr. 2009; 60(sup4): 63–69. PubMed Abstract | Publisher Full Text\n\nFAO/OMS: Norma para alimentos elaborados a base de cereales para lactantes y niños pequeñoS. Codex Alimentarius. Normas Internacionales de los Alimentos, 2009, (Vol. 58, Issue CXS 74-1981). 2013. Publisher Full Text\n\nTrier CM, Johnston CS: Ingestion of nutrition bars high in protein or carbohydrate does not impact 24-h energy intakes in healthy young adults. Appetite. 2012; 59(3): 778–781. Publisher Full Text\n\nRamos-Elorduy J, Pino-M JM, Cuevas-Correa S: Insectos comestibles del estado de México y determinación de su valor nutritivo. Anales del Instituto de Biología Universidad Autónoma de México, serie Zoología. 1998; 69(1): 65–104. Reference Source\n\nDelgado-Vásquez C, Couturier G, Anteparra M: Principales Fitófagos de la Cocona Solanum sessiliforum Dunal (solanaceae) en la Amazonía Peruana. Folia Amazónica. 2022; 20(1–2): 45. Publisher Full Text\n\nAOAC International: Official Methods of Analysis. Gaithersburg, USA: 17ªed.2000.\n\nAOAC: Official Method 920.39 Fat (Crude) or Ether Extract in Animal Feed First Action 1920 Final Action.\n\nNorma Técnica Ecuatoriana INEN 0520: Harinas de origen vegetal, determinación de la ceniza. Primera edición.1981.\n\nNorma Técnica Peruana 201.021:2002 (Revisada el 2015): Carne y productos cárnicos. Determinación del contenido de proteína. 2ª Edición.\n\nLeopold LF, Leopold N, Diehl H: Socaciu C.\"Quantification of carbohydrates in fruit juices using FTIR spectroscopy and multivariate analysis\". Spectroscopy. 2022; 26: 93–104. Publisher Full Text\n\nTorres G, David J, González M, et al.: Análisis del Perfil de Textura en Frutas, Productos Cárnicos y Quesos. ReCiTeIA. 2015; 14(2): 63–75. Reference Source\n\nMárquez-Villacorta L, Pretell-Vásquez C: Evaluación de características de calidad en barras de cereales con alto contenido de fibra y proteína. Biotecnología En El Sector Agropecuario y Agroindustrial. 2018; 16(2): 67–78. Publisher Full Text\n\nSteffolani ME, Bustos MC, Ferreyra ME, et al.: Evaluación de la calidad tecnológica, nutricional y sensorial de barras de cereal con quinoa. AgriScientia. 2017; 34(2): 33. Publisher Full Text\n\nICMSF: Vol.1, 2° Ed., Pág. 132-134, 138, 139-142 (Traducción versión original 1978) Reimpreso 2000 en castellano (Ed. Acribia). Bacterias Coliformes. Recuento de Coliformes Técnica del Número más Probable (NMP). Método 1 (Nortamericano). Bacterias Coliformes. Determinación de Organismos Coliformes de Origen Fecal. Método 1 (Nortamericano). Bacterias Coliformes. Determinación de Organismos Coliformes de Origen Fecal. Pruebas de identificación de Organismos Coliformes IMVIC E. coli Numeración.1983.\n\nICMSF: Vol. 1, 2da. Ed, Pag. 166-167, (Traducción versión original 1978). Reimpresión 2000 en Castellano (Ed. Acribia) Recuento de mohos y levaduras, Método de Recuento de levaduras y mohos por siembra en placa en todo el medio Levaduras Numeración.1983.\n\nICMSF: Vol. 1, 2da. Ed, Pag. 166-167, (Traducción versión original 1978). Reimpresión 2000 en Castellano (Ed. Acribia) Recuento de mohos y levaduras, Método de Recuento de levaduras y mohos por siembra en placa en todo el medio. Mohos Numeración.1983.\n\nAerobios Mesófilos Numeración (Recuento Standar en placa):ICMSF: Vol. 1, 2da. Ed, Pag. 120-124, Met. 1 (Traducción: versión original 1978). Reimpresión 2000 en Castellano (Ed. Acribia) Enumeración de Microorganismos Aerobios Mesófilos - Métodos de Recuento en Placa. Método I, Recuento Estándar en Placa, Recuento en Placa por siembra en todo medio o Recuento en Placa de Microorganismos Aerobios.1983.\n\nNTS N° 071 – MINSA/DIGESA-V.01 del 27 de agosto del 2008, “Norma Técnica Sanitaria que establece los Criterios Microbiológicos de Calidad Sanitaria e Inocuidad para los alimentos y bebidas de Consumo Humano”, para los parámetros microbiológicos. Fuente: NTS N° 071 – MINSA/DIGESA-V.01.\n\nBendezu Ccanto J, Condori Chura J, Lozada-Urbano M: Proximate, microbiological analysis and digestibility of pepsin in atta sexdens flour, from the region of Rioja, Perú. Afr. J. Food Agric. Nutr. Dev. 2022; 22(10): 21938–21951. Publisher Full Text\n\nCosta-Neto EM: Anthropo-entomophagy in Latin America: An overview of the importance of edible insects to local communities. J. Insects Food Feed. 2015; 1(1): 17–23. Publisher Full Text\n\nRamos-Elorduy J: Edible insects: barbarism or solution to the hunger problem. Ethnobiology: Implications and Applications; Proceedings of the First International Congress of Ethnobiology (Belém, 1988). 1990; 151–158. Reference Source\n\nManditsera FA, Luning PA, Fogliano V, et al.: Effect of domestic cooking methods on protein digestibility and mineral bioaccessibility of wild harvested adult edible insects. Food Res. Int. 2019; 121: 404–411. PubMed Abstract | Publisher Full Text\n\nÁlvarez MA: Desarrollo y evaluación de barritas con alto contenido proteico con incorporación de harina de grillo. Universitat Politècnica de València; 2019. Reference Source\n\nBanach JC, Clark S, Lamsal BP: Instrumental and Sensory Texture Attributes of High-Protein Nutrition Bars Formulated with Extruded Milk Protein Concentrate. J. Food Sci. 2016; 81(5): S1254–S1262. PubMed Abstract | Publisher Full Text\n\nHernández-Hernández C, Morales-Sillero A, Fernández-Bolaños J, et al.: Cocoa bean husk: industrial source of antioxidant phenolic extract. J. Sci. Food Agric. 2019; 99(1): 325–333. PubMed Abstract | Publisher Full Text\n\nBchir B, Jean-François T, Rabetafika HN, et al.: Effect of pear apple and date fibres incorporation on the physico-chemical, sensory, nutritional characteristics and the acceptability of cereal bars. Food Sci. Technol. Int. 2018; 24(3): 198–208. PubMed Abstract | Publisher Full Text\n\nGutkoski LC, Bonamigo JMDA, Teixeira DMDF, et al.: Development of oat based cereal bars with high dietary fiber content. Cienc. Tecnol. Aliment. 2002; 27(2): 355–363. Publisher Full Text\n\nFreitas DGC, Moretti RH: Characterization and sensorial evaluation of functional cereal bar. Cienc. Tecnol. Aliment. 2006; 26(2): 318–324. Publisher Full Text"
}
|
[
{
"id": "288948",
"date": "01 Jul 2024",
"name": "Samuel Adelani Babarinde",
"expertise": [
"Reviewer Expertise Entomology and entomophagy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nREVIEWER’S COMMENTS TO AUTHORS\nMANUSCRIPT TITILE: Development and acceptability of a cereal bar with Atta sexdens ant flour\n\nTitle\nModification is suggested Modify as follows: Development and acceptability of a cereal bar with leaf cuter ant, Atta sexdens, flour\n\nAbstract Ln 2-3 Recast as follows:….the regions the central jungle where a leaf cutter ant, Atta sexdens\n\nLn 4-5 Recast as Department of… District of… Province of ……\n\nLn 7-8 13%, 17&, 20% and 23% w/w or v/v or what?\n\nLn 8-9 Recast as follows:… Analyses on moisture, totl fat…. and organoleptic indices (taste, texture, and color) were performed.\nIntroduction Pg 3, Paragraph 2,Ln 2 Change ‘Acheta dometiscus’ to ‘crickets’. The isnect is not a grasshopper.\nChange ‘Cameroon’ to ‘sub -Saharan Africa’ and add the following reference and 6 (Tamesse et al.):\nBabarinde SA, Mvumi BM, Babarinde GO, Manditsera FA, Akande TO, Adepoju, AA. Insects in food and feed systems in sub-Saharan Africa: the untapped potentials. International Journal of Tropical Insect Science. 2021 41 (3): 1923-1951. https://doi.org/10.1007/s42690-020-00305-6\n\nPg. 3, Paragraph 3, Ln 3 …. ‘similar quantities as fish’ or … ‘higher quntities than fish’\n\nPg. 3, Paragraph 3, Ln 4 Change ‘protein from fish’ to ‘relying on insect protein.\n\nPg. 3, Paragraph 4, Ln 2 Recast as follows: Cereals bars are in…….\n\nPg 3, Paragraph 4, Ln 2 Insert ‘and’ before ’compression’\nMethods\nPg. 3, Paragraph 1 ‘ Obtaining Atta sexdens ant’ should be changed to ‘Obtainingleaf cuter ant, Atta sexdens’\nThe first paragraph is not part of what you did. It only provides information about the studied organism (Atta sexdens). Therefore, the content is better placed in the appropriate section of your Introduction.\n\nPg. 3, Paragraph 2 Recast as Department of… District of… Province of ……\n‘This was taken to an electric grinder …..’ should change to ‘This was milled with an electric grinder …..’\n\nPg 3, Paragraph 5 Merge the paragraph with the preceding one.\nGeneral Comments You have to indicate how you formulated your Ant bar mix flour.\n\nPg. 3, Paragraph 6, Ln 3 ..in different concentrations… You need to provide appropriate references.\n\nFigure 1 Change ‘Ceral’ to ‘Cereal’ in the figure legend: Figure 1: Cereal bar…….\n\nPg. 5 Paragraph 1 Which hedonic scale did you use 1-9 or which? The, provide a brief description of what each number stands for.\n\nPg. 5 Paragraph 2 Change ‘data was’ to ‘data were’. Data is plural, while datum is singular\nResults Table 1 Why did you not compare the energy bar with ant flour as FO in Table 1? I feel this is necessary.\n\nTable 2 The methodology that led to your Table 2 is not quite explicit. You would need to improve the appropriate section of your methodology to allow your readers to understand what you did that led to the collection of the data in Table 2.\n\nTable 3 Indicate what F1-F4 stand for as footnote.\n\nFigure 2 Indicate what T1-T2 stand for as figure legend.\n\nPg. 6, Paragraph 2 Did you use 13, 17, 20 and 23% or 15, 20, 25 and 30% ant meal?\n\nFigure 3 Indicate what T15-T30 stand for as figure legend.\nI am of the opinion that you shoud compare your treatments (T1-T4) with the cereal bar without and flour (F0).\nReferences\nAdd this to your references:\n(Babarinde et al., 2021)(Ref-1)\nAbstract Abstract has minor corrections highlighted in my Reviewer's comments to the Authors.\nIntroduction The Introduction also has minor editorial corrections and the need to add more recent references.\nMethods There are few inconsistencies in the methods: for instance, the proportions of ant meal used for the experiment should be clarified.\nDiscussion I feel the cereal bar without ant meal should be used as a standard to establish the results of the experiment.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12626",
"date": "29 Nov 2024",
"name": "Michelle Lozada-Urbano",
"role": "Author Response",
"response": "Dear Reviewer, we appreciate your recommendations for change, each of them has been consistent and the changes have been made in the new document, including the new bibliography."
}
]
},
{
"id": "309763",
"date": "13 Sep 2024",
"name": "Zabentungwa Hlongwane",
"expertise": [
"Reviewer Expertise entomophagy",
"and entomology."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: The title needs to be improved and show that the nutritional composition of cereal bars enriched with ant meal was investigated Abstract: The abstract is good but it lacks a concluding statement what are the implications of the study findings? Keywords: “insect edible” confusing rephrase to edible insects Introduction Paragraph 1 First sentence: Change recommends to recommended Paragraph 1 second sentence: remove capital letter on It Paragraph 1 second sentence: No edible insects do not replace meat, they are sustainable, cheap, and rich in nutrients and can be used to combat malnutrition Paragraph 1 third sentence: “these insects” Which insects are you referring to because no insects were listed before this statement. You must mention the insects that are commonly consumed in the regions that you mentioned because they differ Paragraph 2 last sentence: Atta should be in italics Paragraph 3 second sentence: remove capital letter on In Paragraph 3 last sentence: It would be beneficial to explain why microbiological analysis and consumer acceptability were performed\n\nMaterials and methods The nutrient analysis is not very descriptive, were the samples measured in triplicates or duplicates? Which nitrogen analyzer did the use, and which procedure was used to determine the fat content?\nConsumer acceptability test\nThe methods used are brief and not descriptive for example when were the panelists recruited, where was the study conducted, and where were the panelists seated? How much was the spacing between them? How was the food product presented which labels were used to differentiate between the treatments? Were the panelists selected randomly? What was the ratio of males and females?\nDid the author use 9-point hedonic or 5-point hedonic scales and why? How did you ensure that the panelists were not allergic to edible ants? The panelists only focused on taste. The texture, aroma, and colour were not tested and why? How was the test environment and how did you ensure objectivity in the sensory evaluation method?\nResults The results are not well explained for example the description of results presented in table 2 only focused on protein and fat. What about Ash and carbohydrates? The author needs to say which treatment had the highest nutrients.\nDiscussion In general, the author did not discuss the implications of his/her findings and hardly compared them to the work done by other scholars. In addition, the author needs to explain the cause and effect of his/her findings. The grammar can be improved in the discussion.\nParagraph 1: “The proximate analysis showed that fat and proteins increased as the amount of ant flour increased as well, in comparison with the control bar made without ant flour (F0)” compare your findings with the work of other scholars and explain the factors that might have led to the increase in protein and fat content of energy bars.\nParagraph 1: “Compressibility values ranged from 80.5 N to 117.6 N, and fracturability ranged from 8.48 to 12.33. We did not find any differences among the cereal formulations. All of them showed an acceptability index higher than 95%” compare your findings with the findings of other scholars and explain cause and effect\nParagraph 2: “ A study with ant meal from the Rioja area in Peru showed 35.40% fat, 35.5% protein” It is not clear what was investigated by this mentioned study, in addition, did the fat and protein content increase with the increasing percentage of ant meal added?\nParagraph 2: “It is known that the ants’ abdomen is fatty and that roasted ants are mixed with rice and cassava flour in Brazil and consumed regularly” how is this relevant in this study?\nParagraph 2: “The protein value of insects has a composition similar to vertebrates’ such as pork, chicken, and fish.31 Cephalotes ants have 42.59% protein, chicken 23%, and beef 20%. In addition, insects are high in sodium, potassium, zinc, magnesium, iron, copper, and calcium” How is this relevant to the findings of this study?\n\nParagraph 2: Other cereal bars made with similar products provide a lower amount of protein per serving.” Which similar products? Why did you observe higher protein content while other studies observed lower protein content?\nParagraph 4: “One study compared instrumental sensory texture to the maximum force exerted when biting (shear force), that research concluded that a bar with a higher breaking force might be crumbly but a bar that is easy to crumble does not imply that it requires a higher breaking force” rephrase this sentence and find a better way of reporting this\nParagraph 4: “Marquez L” who is this? Is this supposed to be a citation? Paragraph 4: “According to a study on the addition of chontaduro flour to cereal bars” Chontaduro is not an ant or insect I don’t think it is relevant to compare cereal bars fortified with fruit flour to cereal bars fortified with insect flour as plants and animals have different nutrients and digestability.\nParagraph 4: ”It is expected to observe different resistance characteristics given by the addition of different concentrations of the ingredients during the elaboration of the bars” I don’t think so\nParagraph 5: “One study revealed” this is does not sound right. I suggest you say According to Bchir et al. (2018)…… or Bchir et al. (2018) reported that…..\nParagraph 5: “They found higher acceptability when the bars had medium sugar concentration and high dietary fiber and β-glucan content” This does not make sense, in the previous sentence you said a study by Bschir et al., 2018 revealed however here you are saying they found They found higher acceptability when the bars had medium sugar concentration and high dietary fiber and β-glucan content.……..but you are citing a different author (37).\nParagraph 5: “The formulation de Freitas evaluated was high in protein (15.31%), vitamin E (118.0 mg/100 g). The formulation with 1.1 g/100 g of ascorbic acid added obtained a higher significant sensory preference” this is difficult to follow\nParagraph 6: “The results in this study showed absence of Salmonella, the count of molds and yeasts was 1.0 _ 101 CFU/g, 4.0 _ 101 CFU/g for aerobic mesophiles, and for Escherichia coli the result was <3 NMP/g. You need to explain what your findings mean and what are the implications of this.\nConclusion The conclusion is too brief Any recommendations from the study? What was the significance of this study?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "12666",
"date": "29 Nov 2024",
"name": "Michelle Lozada-Urbano",
"role": "Author Response",
"response": "Dear Reviewer Zabentungwa Hlongwane We appreciate all the comments, we feel that they have helped to improve the paper. Title: The title needs improvement and should indicate that the nutritional composition of cereal bars enriched with ant flour was investigated. The title could be: \"Nutritional Composition and Acceptability Evaluation of Cereal Bars Enriched with Ant Flour (Atta sexdens).\" I have included this in the document. Response: The change was made. Abstract: The abstract is good, but it lacks a concluding statement. What are the implications of the study's findings? Keywords: \"Edible insect\" is confusing; it should be rephrased as \"edible insects.\" Introduction Paragraph 1: First sentence: Change \"recommends\" to \"recommended.\" Response: The word was changed to recommended. Paragraph 1, second sentence: Remove the capitalization in \"It.\" Response: The capitalization was removed. Paragraph 1, second sentence: Edible insects do not replace meat; they are sustainable, economical, nutrient-rich, and can be used to combat malnutrition. Response: This sentence was modified. Paragraph 1, third sentence: \"These insects\" - which insects are you referring to? Because insects were not mentioned prior to this statement. You should mention the insects commonly consumed in the regions you referred to, as they differ. Paragraph 2, last sentence: \"Atta\" should be in italics. Response: The word Atta was italicized. Paragraph 3, second sentence: Remove the capitalization in \"In.\" Response: The capitalization was removed. Paragraph 3, last sentence: It would be beneficial to explain why microbiological analyses and consumer acceptability assessments were conducted. Response: This paragraph was improved. Materials and Methods The nutrient analysis is not very descriptive. Were the samples measured in triplicate or duplicate? Which nitrogen analyzer was used, and what procedure was employed to determine the fat content? Response: Moisture was determined according to AOAC 922.06. Fat was determined according to AOAC 925.09, and extraction was performed using Soxhlet. Ash was determined according to AOAC 923.03. Protein was determined according to AOAC 984.13, using 6.25 as the nitrogen-to-protein conversion factor for all samples; this determination was based on Kjeldahl methodology using conventional analysis. Carbohydrates were calculated by subtracting the percentages of fat, moisture, protein, ash, and carbohydrates from 100%. Analyses were performed in triplicate. Consumer Acceptability Test The methods used are brief and not descriptive. For example, when were the panelists recruited? Where was the study conducted, and where did the panelists sit? What was the spacing between them? How was the food product presented? What labels were used to differentiate between the treatments? Were the panelists randomly selected? What was the gender ratio? Response: The recruitment for the analysis took place in August 2020, in a school environment, and the participants were organized in groups of 10 students who entered according to their arrival at the venue. The study was conducted in a ventilated area, with folders set up containing the samples. The samples were served at room temperature in disposable containers, and each participant was provided with a personal bottle of water. The distance between chairs was one meter, and the labels had three-digit codes assigned to each sample. The percentage of women was 46%. Did the author use 9-point or 5-point hedonic scales, and why? Response: We consider that both scales are essential for measuring consumer preferences and product acceptability. Some advantages of using the 9-point scale are that it allows for capturing subtle differences in consumer preferences compared to the 5-point scale (Wichchukit and O'Mahony, 2015). The 9-point scale also supports more complex statistical analyses that can yield deeper insights into consumer behavior (Wichchukit and O'Mahony, 2015). However, we believe that the number of options can overwhelm respondents, resulting in less reliable data (\"How rating scales influence the reliability of responses, the extreme points, the midpoint, and the preferences of respondents\"). While the 9-point scales provide detailed information, the number of points can be complex and may hinder responses, suggesting that simpler scales could be more effective in certain contexts. Therefore, we decided to use the 5-point scale, as it may be more effective due to its simplicity. Reference: Wichchukit S, O'Mahony M. The 9-point hedonic scale and hedonic ranking in food science: some reappraisals and alternatives. Journal of the Science of Food and Agriculture (2015). doi: 10.1002/JSFA.6993. How did you ensure that the panelists were not allergic to edible ants? Response: They were asked, and none of them had previously consumed any products containing ants. The panelists only focused on the flavor. The color were not evaluated. Why? Response: All samples had exactly the same color. What was the testing environment like, and how was objectivity ensured in the sensory evaluation method? Response: The study was conducted in a ventilated area, with folders set up containing the samples. The samples were served at room temperature in disposable containers, and each participant was provided with a personal bottle of water. The distance between chairs was one meter, and the labels had three-digit codes assigned to each sample. Results The results are not well explained. For example, the description of the results presented in Table 2 only focused on protein and fat. What about ash and carbohydrates? The author needs to indicate which treatment had the highest nutrient levels. Response: Regarding moisture content, no significant difference was found between the formulations. Moisture levels ranged from 17.6 g in formulation F0 to 19.39 g in F2. For carbohydrate content, values varied from 60.65 g in formulation F4 to 66.28 g in F0, with no significant difference found. Although variations in moisture and carbohydrate content were observed in both, these were not statistically significant, suggesting that the variation in ant flour content does not impact these values. The ash analysis revealed significant differences between the formulations. Ash levels ranged from 1.23 g in formulation F4 to 1.86 g in F0. This variability suggests that the mineral composition of the different formulations decreases as the percentage of ant flour increases, which could be associated with the reduction of inputs such as quinoa and kiwicha. Discussion In general, the author did not discuss the implications of their findings and barely compared them to the work of other scholars. Additionally, the author needs to explain the cause-and-effect relationships of their findings. The grammar in the discussion could be improved. Paragraph 1: “The proximal analysis showed that fat and protein increased as the amount of ant flour increased, compared to the control bar made without ant flour (F0).” Compare your findings with the work of other scholars and explain the factors that may have contributed to the increase in protein and fat content in the energy bars. Response: According to authors such as Guan et al. and Kowalski et al., the incorporation of insect flours, including crickets and mealworms, in bread and cakes showed an increase in protein, minerals, and healthy fatty acids (Guan et al., 2024; Kowalski et al., 2022). This result is similar in our cereal bars, where the additional protein allows for greater moisture, making them softer. Q.H., Guan., S., Qian., L., Chen., X.C., Feng. 1. Enhancing the nutritional value of bread by the addition of insect powder: a novel class of food protein additives. Journal of insects as food and feed, (2024). doi: 10.1163/23524588-20230123 Stanisław, Kowalski., Anna, Mikulec., Magdalena, Skotnicka., Barbara, Mickowska., Małgorzata, Makarewicz., Renata, Sabat., Anna, Wywrocka-Gurgul., Aleksandra, Mazurek. 2. Effect of the Addition of Edible Insect Flour from Yellow Mealworm (Tenebrio molitor) on the Sensory Acceptance, and the Physicochemical and Textural Properties of Sponge Cake. Polish Journal of Food and Nutrition Sciences, (2022). doi: 10.31883/pjfns/155405 Paragraph 1: “The compressibility values ranged from 80.5 N to 117.6 N, and the fracturability varied from 8.48 to 12.33. We found no differences between the cereal formulations. All showed an acceptability index above 95%.” Compare your findings with those of other scholars and explain the cause-and-effect relationships. Response: The comparison was made in paragraphs 3 and 4. Paragraph 2: “A study with ant flour from the Rioja region in Peru showed 35.40% fat and 35.5% protein.” It is unclear what was investigated in this mentioned study. Additionally, did the fat and protein content increase with the increasing percentage of added ant flour? Response: The meaning of the sentence was clarified in the complete paragraph. Paragraph 2: “It is known that the abdomen of ants is fatty and that toasted ants are mixed with rice and cassava flour in Brazil and are regularly consumed.” What relevance does this have in this study? Response: This line was removed from the text due to its lack of relevance. Paragraph 2: “The protein value of insects has a composition similar to that of vertebrates, such as pork, chicken, and fish. Cephalotes ants have 42.59% protein, chicken has 23%, and beef has 20%. Additionally, insects are rich in sodium, potassium, zinc, magnesium, iron, copper, and calcium.” What relevance does this have for the findings of this study? Response: It is relevant as it presents a comparison between the protein content of ants and the animal meats we typically consume, such as beef or chicken. Paragraph 2: “Other cereal bars made with similar products provide a lower amount of protein per serving.” What similar products? Why did you observe a higher protein content while other studies reported lower protein content? Response: The comparison is made with the study by Guan, who also finds a high protein and fat content. Paragraph 4: “A study compared instrumental sensory texture with the maximum force exerted when biting (cutting force); that research concluded that a bar with greater breaking force could be brittle, but a bar that is easy to crumble does not imply it requires a greater breaking force.” Reformulate this sentence and find a better way to convey this information. Response: The idea in this paragraph was reformulated. Paragraph 4: “Marquez L” – who is this? Is this supposed to be a citation? Response: This author was correctly cited. Paragraph 4: “According to a study on the addition of chontaduro flour to cereal bars.” Chontaduro is neither an ant nor an insect. I don’t believe it is relevant to compare cereal bars fortified with fruit flour to cereal bars fortified with insect flour, as plants and animals have different nutrients and digestibility. Response: The chontaduro is the larva of the black palm weevil (Rhynchophorus palmarum). The scientific name has been included in the text. Paragraph 4: “Different resistance characteristics are expected to be observed due to the addition of different concentrations of ingredients during the preparation of the bars.” I don't think this is accurate. Response: The resistances were observed according to the percentage of ant flour used. Paragraph 5: “A study revealed” does not sound correct. I suggest saying “According to Bchir et al. (2018)...” or “Bchir et al. (2018) reported that…” Response: This citation was improved as follows: A study by Bchir et al. (2018) revealed that appearance is the main limiting factor for consumer acceptability, especially in cereal bars that include dried fruits as ingredients. Paragraph 5: “They found higher acceptability when the bars had a medium sugar concentration and high dietary fiber and β-glucan content.” This does not make sense. In the previous sentence, you said that a study by Bchir et al. (2018) revealed this, but here you are saying that they found higher acceptability with medium sugar concentration and high dietary fiber and β-glucan content, citing a different author (37). Response: The author Gutkoski found higher acceptability when the bars had medium sugar concentration and high dietary fiber and β-glucan content. Paragraph 5: “The formulation evaluated by Freitas was high in protein (15.31%) and vitamin E (118.0 mg/100 g). The formulation with 1.1 g/100 g of added ascorbic acid achieved a significantly higher sensory preference.” This is difficult to follow. Response: In a study by Gumul, nut bars with the addition of edible insect flours were evaluated, and this addition reduced the perception of most sensory attributes of the bars compared to the standard bar. Paragraph 6: “The results in this study showed the absence of Salmonella, the count of molds and yeasts was 1.0 × 10^1 CFU/g, 4.0 × 10^1 CFU/g for aerobic mesophiles, and for Escherichia coli the result was <3 NMP/g.” You need to explain what your findings mean and what their implications are. Response: The explanation of the findings and their implications was improved. Conclusion: The conclusion is too brief. Response: More conclusions were added to the text. Are there recommendations from the study? What was the importance of this study? Response: A section with some recommendations was added."
}
]
}
] | 1
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https://f1000research.com/articles/12-849
|
https://f1000research.com/articles/12-1523/v1
|
28 Nov 23
|
{
"type": "Research Article",
"title": "Liver metastases from colorectal carcinoma: performance of pathological response scores",
"authors": [
"Sana ben slama",
"Ines Mallek",
"Nadia Ben Othman",
"Bochra Bouchabou",
"Abdelwahab Nakhli",
"Mohammed Hajri",
"Mestiri Hafedh",
"Ahlem Lahmar",
"Dhouha Bacha",
"Sana ben slama",
"Nadia Ben Othman",
"Bochra Bouchabou",
"Abdelwahab Nakhli",
"Mohammed Hajri",
"Mestiri Hafedh",
"Ahlem Lahmar",
"Dhouha Bacha"
],
"abstract": "Background: Pathological response of liver metastases (LM) from colorectal carcinoma (CRC) to neoadjuvant therapy is one of the prognostic factors correlated with recurrence and survival. The aim of this study was to compare the performance of two prognostic scores in patients operated for colorectal cancer liver metastases (CRCLM).\n\nMethods: A study was performed of patients who underwent preoperative chemotherapy (CT), followed by resection of LM, from 2015-2021. Pathological response was evaluated according to Rubbia-Brandt tumor regression grade (TRG) and the Blazer scoring system. Then, we studied the performance of these two prognostic scores, based on homogeneity using the likelihood Ratio (LR+), monotonicity and discriminative ability using the area under the receiver operating characteristic (ROC) curve (AUC).\n\nResults: 70 cases were included in the study. Mean age was 56 years. The sex ratio was 2.2. Forty patients were stage IV (57%) with synchronous all CRCLMs. The overall survival, all stages combined, was 85.5% at 12 months, 41.7% at 24 months and 19.3% at 36 months. The mean survival was better in case of major response (TRG1/TRG2) evaluated at 40.1 and 41.1 months after diagnosis. In cases of partial response (TRG3), the mean survival was 32.1 months. In cases with no response (TRG4/TRG5), survival was estimated at 29.9 and 18.5 months. The Rubbia-Brandt TRG had the highest LR+ (10.95). The LR+ of the Rubbia-Brandt score was greater than 10, so it was a test with very strong contribution. The LR+ of the Blazer score was between 5 and 10, it was a test with strong contribution. The Rubbia-Brandt TRG had the highest linearity value (10.73). With a higher AUC of the ROC curve (0.8), the Rubbia-Brandt TRG was better at predicting survival than the Blazer score.",
"keywords": [
"Colorectal cancers",
"Chemotherapy",
"Surgery",
"Liver metastases",
"Regression",
"Histology",
"Prognosis",
"Survival"
],
"content": "Introduction\n\nColorectal cancer (CRC) ranks third globally as the most commonly diagnosed cancer and second as the leading cause of cancer-related deaths.1 The progression of CRC generally involves metastatic spread and the liver is the most frequently affected site. Rarely 20% of patients, present synchronous liver metastases (LM), while almost 50% will develop them during the course of their illness.2 Surgical resection is considered the most option of treatment for LM, and neoadjuvant chemotherapy (CT) significantly improves prognosis.3 The pathological response of LM to neo-adjuvant therapy is a crucial prognostic factor for recurrence and survival. While the Rubbia-Brandt et al. score4 was the earliest established score to evaluate the tumor response to therapy, other scores, such as that proposed by Blazer et al., have also been suggested.5 However, there is currently no standardized scoring system, and studies evaluating the performance of different scores are yet to be conducted. Therefore, this study aims to assess the tumor response on liver resection specimens histologically, based on the Rubbia-Brandt and Blazer scores after neo-adjuvant treatment, and compare the prognostic performance of these two scores.\n\n\nMethods\n\nThe Ethics Committee for Mongi Slim Hospital La Marsa has examined the study and protocol of the following project: “Liver Metastases From Colorectal Carcinoma: Performance of Pathological Response Scores”. It was made and presented by Dr. MALLEK Ines (Department of anatomopathology). The project does not raise any particular ethical problem.\n\nThe ethics approval was given prior to the start of the study in 2021, in French, as Tunisia is a mainly French speaking country. An updated ethics approval was also provided in English for the purposes of the f1000 submission.\n\nThe approval was registered under number 43/2021 in French version and 27/2023 in English version. Participated in this meeting: PR Lamia BEN JEMAA, Ethics Committee President Mongi Slim Hospital of Marsa and PR Mohamed Sami MEBAZAA.\n\nStudy design: This study was a retrospective, and longitudinal analysis of a single-center series of patients with CRCLM who underwent surgery after neo-adjuvant treatment. All cases were collected from the department of Pathology of the University hospital in north Tunisia (Hospital Mongi Slim) between January 2015 and June 2021.\n\nStudy population: We included patients who met the following criteria: Diagnosis of CRCLM and underwent surgical treatment after neo-adjuvant CT and availability of a detailed anatomical-pathological report. We excluded patients who: Had cancer in another organ, underwent surgery without neo-adjuvant CT. Additionally, patients whose hospital records were unusable or could not be found, and cases with non-usable slides or tissue blocks were excluded from the study. Patients who received other neo-adjuvant treatments (hepatic intra-arterial CT or percutaneous radiofrequency) were also excluded.\n\nData collection: We collected epidemiological, clinical, and biological data, as well as information on primary CRC, CRCLM, types of neo-adjuvant therapy initiated, type of surgical procedure performed, follow-up, and outcome for all patients included in the study.\n\nPathological study: Based on the pathology report, we recorded the location, number, and size of the CRCLM. All slides were reviewed by two senior pathologists. We assessed the degree of tumor response or Tumor Regression Grading (TRG) according to: The Rubbia-Brandt score4 and the Blazer score.5 We also recorded the following tumor characteristics: The state of the resection margins (R0 if safe or R1 if less than 1mm), the presence or absence of vascular emboli, and endobiliary extension.\n\nStatistical analysis: The data was entered using SPSS® version 24.0. Descriptive and analytical studies were conducted. Mortality was assessed by actuarial survival curves using the Kaplan Meier model. The comparison of survival curves was performed by the Log Rank test. The performance of each score was assessed by the following criteria: homogeneity, monotonicity, and discriminatory capacity. The significance level was set at 0.05.6,7\n\n\nResults\n\nWe included 70 patients in our study. 48 were male (69%), giving a sex ratio (male/female) of 2.2. The average age of the patients was 56 years. In 54 cases (77%) it was a colon cancer, in 16 cases (23%) rectal cancer. In 64 cases (92%), it was adenocarcinoma without other specifications (SAI). We found five cases of mucinous adenocarcinoma (7%), and only one case of adenosquamous carcinoma. The SAI adenocarcinomas were all low grade. The most frequent stage at diagnosis was stage IV with synchronous metastases, all of which were in the liver (40 cases, 57%). All patients underwent carcinological surgical resection according to the initial tumour site.\n\nTime to onset of liver metastases: Forty patients (57%) had at least one synchronous LM. Thirty patients (43%) had metachronous LM. The mean time to onset of metachronous LM was 10 months.\n\nNeo-adjuvant treatment modalities: Of our patients, 47 received CT alone (67%) and 23 received CT plus targeted therapy (33%). The most represented CT regimen was FOLFOX (Folinic acid + 5FU + Oxaliplatin), used in 63 patients (90%). The average number of courses administered was estimated at 6 courses (extremes between 2 and 12 courses).\n\nSurgical treatment of liver metastases: CRCLMs were bi-lobar in 63% of cases (44 cases) and uni-lobar in 37% (26 cases). Anatomical hepatectomy (lobectomy/segmentectomy) was performed in 28 cases (40%) and non-anatomical (metastasectomy or wedge resection) in 42 cases (60%).\n\nPathological characteristics of liver metastases: The average number of LMs was three (extremes of 1 to 12 per patient) and the mean lesion size was 25 mm (range 2-130 mm). The LMs were in 43% (30 cases) in the right lobe and in 20% (14 cases) in the left lobe. They were bi-lobar in 37% of cases (26 cases). According to Rubbia-Brandt score, the CRCLMs were classified into TRG 1 in eight cases (11%), TRG 2 in eight cases (11%), TRG 3 in 17 cases (24%), TRG 4 in 30 cases (43%), TRG 5 in seven cases (10%). And according to Blazer, five patients (7%) had a complete pathological response, 34 patients (49%) had a minor response and 31 (44%) had a major response. The resection margins of LM were R0 in 59 resection pieces (77%) and invaded (R1) in 11 cases (16%). We also found vascular emboli in six patients (9%). Only one patient had endo-biliary extension. Moreover, Six of the 45 patients had lymph node metastases.\n\nAbundant fibrosis and rare residual carcinomatous structures (arrow). According to Blazer, this is a major pathological response and TRG2 according to Rubbia-Brandt (HEx25).\n\nPredominant fibrosis with scattered residual tumour cells: According to Rubbia-Brandt, partial response (TRG 3) and according to Blazer, this is a major pathological response (presence of 1 to 49% residual tumour cells) (HEx20).\n\nMicroscopic examination of the liver parenchyma remote from the CRCLMs showed the presence of chemo-induced lesions in 42 patients (60%): 18 cases (26%) of vascular lesions (sinusoidal obstruction syndrome), 13 cases of steatosis (19%), one case of steatohepatitis and 10 cases with associated lesions (14%).\n\nOverall survival for all stages was 85.5% at 12 months, 41.7% at 24 months and 19.3% at 36 months. There was a significant difference in survival between the different grades for Rubbia- Brandt TRG (p=0.03) but not for Blazer TRG (p=0.269). For Rubbia-Brandt TRG, the mean survival was better in the case of a major response (TRG 1/ TRG 2) assessed at 40.1 and 41.1 months after the initial diagnosis. In the case of partial response (TRG 3), the mean survival was 32.1 months. In cases of no response (TRG 4/TRG 5), survival was estimated at 29.9 and 18.5 months. For Blazer, the mean survival was greater for complete response, estimated at 41.1 months after initial diagnosis. For the major response group, survival was estimated at 38.2 months. For the minor or no response group, survival was 29.3 months. When discussing homogeneity, the likelihood ratio χ2 (LR) for The Rubbia- Brandt TRG had the highest LR+. Rubbia-Brandt has a score of 10.953 and Blazer has a score of 7.246. The RV+ of the Rubbia-Brandt score was greater than 10, so it is a score with very strong diagnostic contribution. The RV+ of the Blazer score was between 5 and 10, so it is a score with strong diagnostic input. When looking at monotonicity with the linear trend χ2, of the two scores, the Rubbia-Brandt TRG had the highest linearity value. Rubbia-Brandt has a score of 10.738 and Blazer has a score of 4.446. Looking at the Discriminatory capacity, we can see a sensitivity and specificity of scores for survival prediction. The graphical representation of the predictive capacity of each score for survival is the AUC of the ROC curve is as follows the Figure 1. The Rubbia-Brandt score was a good performing score as its AUC under the ROC curve was 0.8. The Blazer score was a poorly performing score as its AUC under the ROC curve was 0.6. The Rubbia-Brandt TRG score was better at predicting survival than the Blazer score (p=0.003).\n\n\nDiscussion\n\nIn this study, 70 patients were included with an average age of 56 years and a sex ratio of 2.2. 57% of patients were stage IV at diagnosis with synchronous LM. The Rubbia-Brandt TRG and the Blazer score were used to classify patients' pathological responses. The Rubbia-Brandt TRG classified 11% of LMs as TRG 1, 11% as TRG 2, 24% as TRG 3, 40% as TRG 5, and 10% as TRG 5. The Blazer score showed that 7% of CRCLMs had a complete pathological response, 49% had a minor response, and 44% had a major response. The overall survival rate for all stages was 85.5% at 12 months, 41.7% at 24 months, and 19.3% at 36 months. Patients who had a major response had better mean survival at 40.1 and 41.1 months, while patients with partial response had a mean survival of 32.1 months. Patients with no response had a survival of 29.9 and 18.5 months. The Rubbia-Brandt TRG score had a higher RV+ value and linearity value compared to the Blazer score. The Rubbia-Brandt TRG score also performed better in predicting survival with an AUC of 0.8, while the Blazer score had an AUC of 0.6. The study concluded that the Rubbia-Brandt score is a good tool for assessing pathological response of CRCLM after neoadjuvant therapy and can be used in daily practice.\n\nThe retrospective nature of the study with some incomplete clinical or complementary data, and heterogeneity in treatment protocols may have affected the therapeutic response, the results of both scores and the prognosis of patients. The inter-observer variability for each of the two scores was not studied.\n\nPreoperative factors such as the time of onset of LM and the impact of neoadjuvant CT on overall patient survival were found to be significant factors. The number and size of CRCLMs were also important, with recent studies showing that tumors larger than 10 cm had a poor prognosis.8 The quality of surgical resection was found to be an important prognostic factor.9 Pathological factors of invasion were also found to be associated with a significant reduction in overall survival [68,69]. Tumor regression after neo-adjuvant treatment was assessed using the Response Evaluation Criteria in Solid Tumors radiology system [73]. However, it was shown that better survival is not always associated with a good radiological response, especially after targeted therapy whose mechanism of action is mainly cytostatic rather than cytotoxic [72]. Pathological response on the surgical specimen was found to be an accurate means of assessing response to systemic therapy.10,11 The presence of systemic treatment-induced liver injury was also found to have an important prognostic impact.3\n\nIn 2006, Rubbia Brandt and colleagues elaborated the first pathological response score for CRCLM4 based on Mandard's12 score for oesophageal and rectal cancers. The study included 525 CRCLM resected from 181 patients comparing a group of 112 patients who received different neo-adjuvant CT regimens (5FU, FOLFOX, FOLFIRI and FOLFOXIRI) versus a control group of 69 patients who underwent surgical resection only. Assessment of pathological tumour regression was scored by two independent pathologists using a semi-quantitative five-category system, which assesses the relative proportion of tumour cells and fibrosis. Thus, the Rubbia-Brandt TRG was as follows: TRG1: Extensive fibrosis, no tumour cells, TRG 2: Abundant fibrosis interspersed with few residual tumour cells, TRG 3: Predominantly fibrosis with more residual tumour cells, TRG 4: Predominantly tumour cells over fibrosis, TRG5: Tumour cells without fibrosis. This score did not include necrosis, as it would be a rather spontaneous phenomenon related to the tumour and not to the cytotoxic effects of CT. In the series studied by Rubbia-Brandt et al,4 pathological regression was significantly better (p<0.0001) in patients who received neo-adjuvant CT compared to the control group (surgical treatment only). In our study, eight LMs (11%) were classified as TRG1, eight LMs were classified as TRG2 (11%), 17 LMs were classified as TRG3 (24%), 30 LMs were classified as TRG4 (40%) and finally seven LMs (10%) were classified as TRG5.\n\nThe prognostic value of a “partial response” would be important. Indeed, several meta- analyses have argued that near-complete regression has a better prognosis than partial regression, as applied in gastro-oesophageal cancers.14,15 This system has the advantage of being congruent on the system used for primary CRC, recommended by the American Joint Committee. This allows easy comparison of pathological regression between the primary and metastatic sites. In the original study by Rubbia-Brandt et al,4 the five-year overall survival was 41. The rate of response in patients with LM classified as TRG 1-2 and 38% for LM with TRG 3, compared to 9% in patients with LM without pathological response TRG 4-5. Overall survival at 5 years was significantly better in LM with complete or near- complete response (TRG 1-2) as well as in LM with partial response (TRG3) compared to LM without response (p = 0.0003 and p =0.0019 respectively).\n\nThere is an individualisation of a 'complete response' group and the system must be designed to identify a ‘strong response’ to CT, to which the ‘complete response’ belongs. Indeed, a difference between the ‘complete response group’ and the ‘low viable cell group’ can be attributed to treatment sensitivity and a lack of sampling on macroscopy. In addition, TRG2 corresponding to the presence of ‘rare’ residual tumour cells would lack precision. Indeed, do ‘rare’ tumour cells correspond to isolated cells or to small groups of tumour cells? A percentage with precise cuts-off to quantify residual tumour cells would be useful to limit this subjectivity and improve reproducibility5 (Figure 2). Then, the use of two components to develop the TRG: tumour cells and fibrosis. In practice, the use of a single component in the scoring scale should be more widely and easily applicable to clinical practice. This prompted a Canadian team to propose a tumour regression score: Pathological Response Grade (PRG), defined by a single criterion; the percentage of viable tumour cells correlated with survival. Patients with a strong PRG (<10% viable tumour cells in all resected lesions) had significantly better survival and significantly longer recurrence-free survival (an independent predictor of survival).16 Nevertheless, larger series would be needed to prospectively validate this system. Finally, the treatments used in the Rubbia-Brandt et al. study only take into account the use of FOLFOX and FOLFIRI protocols without bevacizumab and cetuximab. Targeted therapies have been shown to be intrinsically effective.17\n\nIn 2008, Blazer et al. conducted a retrospective study of 305 patients who received induction the therapy (FOLFOX or FOLFIRI, with or without bevacizumab) followed by CRCLM resection. The pathological regression study was semi- quantitative based on the percentage of viable tumour cells remaining. The score is made up of three groups: Complete pathological response: absence of residual tumour cells, Major pathological response: presence of 1 to 49% residual tumour cells, Minor pathological response: presence of more than 50% residual tumour cells.\n\nPatients without pathological regression (100% residual tumour cells) are included in the minor response group. If multiple metastases exist, the pathological response is the average of the scores of the individual tumour nodules. Of our 70 patients, five patients (7%) had a complete pathological response, 34 patients (49%) had a minor response and 31 (44%) had a major response. Overall survival was significantly different between the three response groups.\n\nIn the original study by Blazer et al,5 the 5-year overall survival was 75% for complete responders and 56% for major responders, compared to 33% for minor responders.\n\nThe 5-year overall survival was significantly better in patients with a complete response compared to those with a major response (p=0.037). The difference in overall survival between patients with a major response and those with a minor response was also significant (p=0.028).\n\nIn our study, the complete pathological response group had the best survival but no significant difference with the other two groups.\n\nThe Blazer score has several limitations. Firstly, subjectivity and inter-observer variability have been widely reported,13 indicating inconsistent interpretations among different observers. Secondly, the score relies on estimating the initial tumor area, which can be challenging to determine accurately. Thirdly, when identifying the ‘major response’ group, it considers the presence of a lower percentage of viable tumor cells as the defining factor. However, the threshold of 50% viable tumor cells seems less specific as a marker for a pathological response to CT, especially considering that necrosis or fibrosis can be seen in LM without any CT treatment.4\n\nAn ideal grading system should assess the therapeutic response and prognosis in a reproducible and accurate way. To date, the optimal score for assessing pathological response remains a matter of debate. To our knowledge, no study has compared the performance of pathological regression scores of operated RCCs. We studied the predictive capacity of the two scores for survival based on the ROC curve with AUC measurement. We found that the Rubbia Brandt ROC system was 0.8, higher than the Blazer score which was 0.6. Thus, the Rubbia-Brandt TRG is a score with a better performance. Similarly, the homogeneity and linear capacity of the two regression scores were studied. We found that the RV+ Rubbia Brandt score4 was higher than 10. It is therefore a test with a very strong contribution. The Blazer score5 had an RV+ between 5 and 10. It is therefore a test with a strong contribution. Of the two scores, the Rubbia-Brandt TRG had the highest linearity value (10.73). Although both scores were predictive of mean survival, the Rubbia-Brandt TRG system performed better in our study. It is a more detailed five-level score, which looks at the response of the tumour to the treatment given, reflected by pathological changes, especially fibrosis. This is significantly correlated with better survival.18 The three-level Blazer score would be more stable in terms of consistency but the addition of levels in the score could provide additional prognostic information. We note an important limitation between these two systems. This is the category ‘almost complete regression’ which can be very subjective. Indeed, TRG 3 according to Rubbia-Brandt has been defined as \"Presence of residual tumour cells scattered within predominantly fibrous territories\".4 This category is equivalent to \"major regression, <50% residual tumour cells\" according to the Blazer score5 (Figure 3). Rubbia-Brandt and Blazer systems may be inaccurate in predicting prognosis, especially in N+ or R1 patients. Consideration of regional N status and margin status could improve the prognostic ability of these grading systems that assess LM only. These criteria must be taken into account and reported in the pathology reports. A final point is that these two scores do not seem to take into account intra-tumour heterogeneity. Indeed, for patients with multiple LM, the highest TRG is taken into account, which does not reflect the heterogeneity observed among metastatic lesions. The TRG of Rubbia-Brandt thus ignores the regression status of all but the worst of the tumours.19 Blazer's score considers the average response of all tumours, whereas there is evidence that at least one of several LMs with complete pathological response is associated with a better prognosis.20 This highlights that intra-tumour response variations should not be neglected. Thus, detailing each score for each LM seems more accurate.\n\nA strong and valid pathological regression system will be integral to establishing a standard in the analysis of resected CRCLM. Prospective studies with large cohorts are needed to ensure standardisation of macroscopic management protocols, determine the reliability and inter-observer variability of any monitoring pathological system notation, to accurately define and validate the prognostic value of a pathological regression score, integrate pathological regression systems and other pathological parameters into a standardised treatment algorithm for CRCLM.\n\nA difficult aspect of conducting a multi-institutional study will be the standardisation of treatment. According to our results, the use of the Rubbia Brandt TRG should be integrated into the daily practice of pathologists for a better management of CRCLM liver resection specimens after neo-adjuvant therapy. Its predictive value for survival has been widely proven.\n\nThe Rubbia Brandt TRG system can complement the post neoadjuvant pTN stage (ypTN) and other pathological criteria that have a strong correlation with survival. Their combination is thus more predictive of survival. It would be interesting to complete our work with prospective, larger sample, multicentre studies, taking into account the clinical, radiological and evolutionary data of the patients.\n\n\nConclusion\n\nIn conclusion, surgical resection remains the gold standard treatment for CRCLM, and the prognosis is significantly improved with the use of neoadjuvant chemotherapy (CT). Pathological response to neo-adjuvant therapy is a crucial prognostic factor correlated with recurrence and survival. The Rubbia Brandt TRG system can complement the ypTN stage and other pathological criteria to improve the predictivity of survival.",
"appendix": "Data availability\n\nFigshare. Data Liver Metastases From Colorectal Carcinoma: Performance Of Pathological Response Scores. DOI: 10.6084/m9.figshare.23620656\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).\n\n\nReferences\n\nIARC - International Agency for Research on Cancer. Cancer [En ligne]. 2022 [cité 23 sept 2022]. Reference Source\n\nMella J, Biffin A, Radcliffe AG, et al.: Population-based audit of colorectal cancer management in two UK health regions. Colorectal cancer working group, royal college of surgeons of England clinical epidemiology and audit unit. Br. J. Surg. 1997 Dec; 84(12): 1731–1736. Publisher Full Text\n\nPassot G, Soubrane O, Giuliante F, et al.: Recent advances in chemotherapy and surgery for colorectal liver metastases. Liver Cancer. 2016 Nov; 6(1): 72–79. PubMed Abstract | Publisher Full Text\n\nRubbia Brandt L, Giostra E, Brezault C, et al.: Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann. Oncol. 2007 Feb; 18(2): 299–304. PubMed Abstract | Publisher Full Text\n\nBlazer DG, Kishi Y, Maru DM, et al.: Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J. Clin. Oncol. 2008 Nov; 26(33): 5344–5351. PubMed Abstract | Publisher Full Text\n\nUeno S, Tanabe G, Sako K, et al.: Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 japanese patients. Cancer of the liver italian program. Hepatology. 2001 Sep; 34(3): 529–534. PubMed Abstract | Publisher Full Text\n\nSwets JA: Measuring the accuracy of diagnostic systems. Science. 1988 Jun; 240(4857): 1285–1293. Publisher Full Text\n\nPhelip JM, Tougeron D, Léonard D, et al.: Metastatic colorectal cancer (mCRC): french intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig. Liver Dis. 2019 Oct; 51(10): 1357–1363. PubMed Abstract | Publisher Full Text\n\nTharin Z, Blanc J, Alaoui IC, et al.: Influence of primary tumor location and resection on survival in metastatic colorectal cancer. World J. Gastrointest Oncol. 2020 Nov; 12(11): 1296–1310. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChun YS, Vauthey JN, Boonsirikamchai P, et al.: Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. J. Am. Med. Assoc. 2009 Dec; 302(21): 2338–2344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReddy SK, Parker RJ, Leach JW, et al.: Tumor histopathology predicts outcomes after resection of colorectal cancer liver metastases treated with and without pre-operative chemotherapy. J. Surg. Oncol. 2016 Mar; 113(4): 456–462. PubMed Abstract | Publisher Full Text\n\nBouzourene H, Bosman FT, Seelentag W, et al.: Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002 Feb; 94(4): 1121–1130. PubMed Abstract | Publisher Full Text\n\nViganò L, Capussotti L, De Rosa G, et al.: Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival. Ann. Surg. 2013 Nov; 258(5): 731–742. Publisher Full Text\n\nCai Y, Lu X, Zhu X, et al.: Histological tumor response assessment in colorectal liver metastases after neoadjuvant chemotherapy: impact of the variation in tumor regression grading and peritumoral lymphocytic infiltration. J. Cancer. 2019 Oct; 10(23): 5852–5861. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaldin P, Van Den Eynde M, Hubert C, et al.: The role of the pathologist and clinical implications in colorectal liver metastasis. Acta Gastroenterol. Belg. 2018 Jul; 81(3): 419–426.\n\nTomasello G, Petrelli F, Ghidini M, et al.: Tumor regression grade and survival after neoadjuvant treatment in gastro- esophageal cancer: a meta-analysis of 17 published studies. Eur. J. Surg. Oncol. 2017 Sep; 43(9): 1607–1616. PubMed Abstract | Publisher Full Text\n\nKong JC, Guerra GR, Warrier SK, et al.: Prognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta-analysis. Color. Dis. 2018 Jul; 20(7): 574–585. PubMed Abstract | Publisher Full Text\n\nChan G, Hassanain M, Chaudhury P, et al.: Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB. 2010 May; 12(4): 277–284. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNordlinger B, Adam R, Arnold D, et al.: The role of biological agents in the resection of colorectal liver metastases. Clin. Oncol. 2012 Aug; 24(6): 432–442. Publisher Full Text\n\nPoultsides GA, Bao F, Servais EL, et al.: Pathologic response to preoperative chemotherapy in colorectal liver metastases: fibrosis, not necrosis, predicts outcome. Ann. Surg. Oncol. 2012 Sep; 19(9): 2797–2804. Publisher Full Text"
}
|
[
{
"id": "227155",
"date": "20 Dec 2023",
"name": "Maroua Brahimi",
"expertise": [
"Reviewer Expertise Pathology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the paper \" Liver metastases from colorectal carcinoma: performance of pathological response scores\", the authors evaluate the pathological response and compare the performance of two prognostic scores : Rubbia-Brandt tumor regression grade (TRG) and the Blazer scoring system, in a population of 70 patients with liver metastases from colorectal cancer . The conclusion is that the Rubbia-Brandt TRG was better in predicting survival, which is well known.The study is not novel and the aim of the study isn't contibutive to the field (1). Overall, the precision of the manuscript does not reach the acceptable standards, there are so many methodological errors: How the specimen was prepared? How the cases with more than one liver metastase were evaluated?.......(1), (2). Many sources of heterogenicity: for example all the histologic types were included....The statistical results lacks clarity and representativity (tables, figures...) (1).\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "278480",
"date": "21 May 2024",
"name": "Luckshi Rajendran",
"expertise": [
"Reviewer Expertise clinical epidemiology",
"transplantation",
"liver cancer",
"surgery"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article by Ben Slama et al., provides a retrospective review of the performance of two prognostic scoring system based on assessment of pathologic response following neoadjuvant chemotherapy and liver resection for colorectal liver metastases. We would like to commend the authors for their efforts; however, we would like to raise the following points/ concerns:\n\nAbstract: 1. For the sex ratio, the comparator is needed, otherwise unable to deduce without assumption. Alternatively mentioning % of males (or alternatively females) could be considered. 2. Background and methods imply that all have tumors are stage IV (i.e. CRLM) – is 57% meant to indicate synchronous, and rest is metachronous? This is unclear/ inaccurate -should be rephrased. Similarly, the next sentence referencing “all stages combined” is confusing - these theoretically are all stage IV disease 3. Please incorporate statistical significance in comparison for survival estimates based on TRG1-5. Also, why do you use mean (overall?) survival and not median? 4. Please show 95%CI of the AUC. 5. Conclusions/Discussion section is missing in the abstract.\n\nIntroduction:\n1. Global disease burden (i.e. first sentence): we recommend to reference the original data source from WHO from the global cancer observatory 2. This paragraph needs to be proofread – grammar/ missing words, does not flow overall 3. Please add a statement on resectability considerations of CRLM, especially given only subset of patients are resection candidates 4. We recommend implementing guideline references (e.g. [Ref-1] ) and the original references for the neoadjuvant trials 5. The gap in knowledge statement needs to be rephrased, because of lack of accuracy.\n\nMethods:\n1. Please include the different neoadjuvant chemotherapy treatment regimens and dosages. Additionally, RFA for CRLM is not considered a neoadjuvant treatment – it can be used in realm of curative. I would focus solely on neoadjuvant chemotherapy in this paper. Similarly use of HAIP may be a different population of patients with initially unresectable disease, can be confusing also when lumped in with population that received IV chemo alone 2. Please include last date of follow-up included. 3. Was normality of data distribution assessed? 4. Which statistical test were used to compare pathological responses? Please write in more detail about your diagnostic performance analysis, which tests were used? 5. For survival analysis we recommend to read [Ref-2,3].\n\nResults: 1. How many left sided vs. right-sided tumours; Please also include other factors like presence of RAS mutation, BRAF status? 2. Is this all liver-only mets (i.e. extrahepatic mets excluded)? What is the percent of major vs. minor hepatectomy? What was done with the primary tumour in all of these cases? 3. Please consider including a CONSORT diagram, to allow the reader to assess the potential degree of selection bias, as you excluded patients based on ‘hospital records were unusable or could not be found, and cases with non-usable slides or tissue blocks’. 3. Same here as within the abstract, was 57% synchronous and 43% metachronous? Otherwise your selection criteria are not coherent. 4. Figure 1 and figure 2 are mixed up in the manuscript. Please fix 5. Consider reporting the T, N and M status of your cohort. 6. Please consider including the Kaplan Meier curve stratified by your regression grades. 7. Same here, why do you report mean survival and not median survival?\nDiscussion:\n1. Too long, reads like a review, please consider restricting it to what is related to this study. Consider restructuring into five paragraphs with: (1) key findings, (2) strengths and limitations, (3) comparison with similar research, (4) explanations of findings and (5) implications and actions needed.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-1523
|
https://f1000research.com/articles/13-188/v1
|
11 Mar 24
|
{
"type": "Research Article",
"title": "Impacts of illegal trade on socio-emotional and behavioural skills in macaques",
"authors": [
"Amapola Rey",
"Maria Padrell",
"Miquel Llorente",
"Amapola Rey",
"Maria Padrell"
],
"abstract": "Decades of research have illuminated the consequences of early adverse rearing experiences in laboratory macaque populations. However, limited knowledge exists about the impact of traumatic episodes in non-laboratory environments. This study delves into the repercussions of illegal trade on socio-emotional and behavioural skills in five macaque species, all victims of poaching. We categorised their past experiences into seven aspects, encompassing maternal care and interactions with conspecifics. We assessed social engagement and cooperation by analysing social behaviours and employing the Social Responsiveness Scale. Emotional resilience was evaluated by measuring anxiety levels and the occurrence of abnormal behaviours, supported by a welfare questionnaire. Additionally, the introduction of Cattell’s 16PF questionnaire in macaques for the first time aimed to reveal the influence of traumatic experiences on their personality traits. Our findings emphasise the significance of early social exposure. The lack of juvenile social contact predicts reduced social behaviours and an inclination towards social avoidance in adulthood. Macaques raised by humans tend to exhibit more abnormal behaviours in social contexts, compromising their welfare. Deprivation of social exposure in infancy negatively impacts psychological stimulation and overall welfare. The duration of time spent in illegal trade correlates with heightened anxiety levels. Personality traits such as ‘Calmness’ and ‘Unfriendliness’ are influenced by rearing conditions, with macaques deprived of social interaction during their early years showing higher levels of introversion. In conclusion, the absence of social exposure during early life and hand-rearing due to illegal trade significantly shape macaques’ personality traits and their social and emotional skills.",
"keywords": [
"Wildlife trade",
"welfare",
"social responsiveness",
"personality",
"behaviour",
"macaques"
],
"content": "Introduction\n\nMacaques have been widely utilised as model organisms in advancing our understanding of various human pathologies, including psychological and neurodevelopmental disorders.1,2 This preference can be attributed to the substantial commonalities shared between humans and macaques, such as their tendency to live in large social groups, undergo similar developmental stages, and share cognitive and socio-emotional attributes.1–3 The early years of development represent a particularly vulnerable stage during which high stress exposure or adverse experiences can exert profound influences on brain development. Subsequently, this can lead to deleterious behavioural, cognitive, or emotional outcomes4,5 (e.g., for review in macaques see Ref. 6). In humans, “adverse childhood experiences” (ACE) or “children adversity” refer to detrimental environmental experiences during infancy. These experiences encompass physical maltreatment (involving violence, the threat of mistreating, or sexual abuse), emotional abuse (distress), as well as the deprivation of essential inputs such as cognitive and social withdrawal, and neglect.7,8 These proximal processes during early life are intricately associated with impaired socio-emotional and behavioural (SEB) capacities in adulthood in both humans,9 and macaques.10,11 Zhang (2017)6 reviewed the effects of early adverse rearing experiences (EARE), similar to ACE in the context of children, in non-human primates, mostly using Rhesus macaques (Macaca mulatta) as a model species. Many skills and characteristics seem to be affected by EARE. For instance, it is noteworthy that social skills may decline as a result of an increased manifestation of stereotypes, abnormal, and anxiety-like behaviours.12–15 Similarly, Bellanca and Crockett (2002)16 revealed that the expression and manifestation of abnormal behaviours and stereotypes in pig tailed macaques (Macaca nemestrina) used in invasive research depended on the rearing and housing, being the former condition crucial for locomotor stereotypes exhibition. Lutz and colleagues (2003)17 underpinned these results in captive Rhesus monkeys. The research group found that nurse rearing represented a risk factor for the development of digit-sucking behaviours, whereas, the age at which macaques were individually housed in cages dramatically impacted on the rate of repetitive behaviours, including self-directed stereotypes, self-injury, and self-biting abnormal behaviours. These studies evidenced the critical role of social contact during infancy and juvenility in shaping the normal development of SEB skills within macaque species. In line with this, several studies revealed that early abused macaques housed at research facilities show long-term effects such as cognitive impairment,18–20 socio-behavioural deficiencies,21 including less play, lower social rank, and an increased frequency of aggressive behaviour.22 Additionally, they may exhibit, impaired sexual behaviour,23–27 a reduced repertoire of species-typical behaviours,28 maternal neglect and abuse towards offspring,29–31 and lower social skills in adulthood.32–34 Furthermore, they can experience psychophysiological impacts, notably the dysregulation of the hypothalamic–pituitary–adrenal axis (e.g., for reviews see Ref. 35). The capacity of individuals to withstand and recover from these traumatic experiences varies significantly and is influenced by a multitude of factors, that include species differences, the age at which the separation from the mother occurs, individual personality traits, and the presence of a secure attachment during infancy.11,36\n\nOn the top of that, infant and early adolescent trauma may serve as specific vulnerability and mediator factors contributing to several psychological disorders, including post-traumatic stress disorder (PTSD), major depressive episodes, anxiety disorders, cognitive impairment, and emotional dysregulation in both human and macaques.1,2,37,38 In this vein, McLaughlin and colleagues (2019)39 have explored the neurodevelopmental mechanisms that underlie the boundary between adverse childhood experiences (ACE) in children and psychopathological outcomes in adulthood, including PTSD, major depressive episodes, anxiety, and cognitive impairment. Likewise, Ausderau and colleagues (2023)40 compared the symptoms of depression and anxiety between humans, marmosets, Rhesus and long-tailed macaques. The vast majority of cited papers on this research focused on severe life experiences and their role in the development of aforementioned disorders, such as maternal separation,41–45 early social withdrawal,46,47 and early adverse rearing conditions.48,49\n\nWhile extensive literature has been dedicated to the study of early severe experiences in laboratory macaques,50,51 our understanding of the consequences of such conditions during infancy, juvenility, or across the lifespan in (former) captive macaques, especially those affected by (illegal) trade or poaching, remains limited. This knowledge gap is of paramount importance for the conservation of primates. According to The IUCN Red List of Threatened Species, long-tailed macaques (Macaca fascicularis) are dramatically threatened by national trade for pets, entertainment purposes for tourists, and social media exploitation. Furthermore, the international trade in this species has burgeoned into a multi-billion-dollar industry, a trend that has increased even more in the wake of the Covid-19 pandemic.52 In the case of the Northern pig-tailed macaques (Macaca leonina), their principal threats in Lao PDR, Vietnam, and Cambodia stem from bushmeat and the pet trade. In Thailand, males of this species are subjected to exploitation, as they are trained for coconut harvesting and may subsequently be sold for up to $1000.53,54 Similarly, in Lao PDR the primary threats for the stump-tailed macaque (Macaca arctoides) and Assam macaques (Macaca assamensis) include bushmeat, traditional medicine, and the pet trade, being their bones sold in local markets or through social media platforms for the production of glue or balms.55,56 Globalisation and the prevalence of social media exacerbate this dire situation. For instance, Espinosa & Dias (2016)57 revealed that non-human primates face heightened risks due to interactions with tourists seeking wildlife selfies, thereby contributing to the potential risk of poaching.58 Furthermore, unpublish results declared that a staggering number of over 4,700 long-tailed macaques were offered for sale on Facebook in Indonesia in the years 2020 and 2021 alone (source: IUCN). Meanwhile, the lack of strong wildlife policies in Southeast Asia contributes to this problematic situation. For instance, the Organisation for Economic Co-operation and Development (OECD) underscore in its publication “The Illegal Wildlife Trade in Southeast Asia” (2019)59 the pressing need for effective enforcement of anti-trafficking laws, along with the strengthening of penalties and financial consequences to deter the persisting high-reward, low-risk nature of wildlife trade. As an example, we can highlight “The Wildlife and Aquatic Law 2007” (WAL, 2007) implemented in Lao PDR for the protection of wildlife. This legislation permits the holding of wildlife for breeding and business purposes, criminalises poaching of endangered species, as well as, their illegal trade and commercialisation. Nonetheless, the penalties for violating this law range from imprisonment maximum two years and maximum fine is 600,000 LAK, equivalent to 72 USD.60\n\nDespite these facts, little is known on whether being a victim of the trade along lifespan shapes several socio-emotional and behavioural skills or personality traits and its potential impacts on the quality of life in non-human primates. Lopresti-Goodman and colleagues (2013)61 presented two case studies of rescued chimpanzees from bushmeat and pet trade whose psychological distress—based on abnormal behaviour, stereotypes, social deprivation, hypervigilance, fear, emotional instability and even symptoms of PTSD in adulthood—was linked to abusive experiences in infancy and juvenility and lifelong captivity. Regarding personality traits, Ortín and colleagues (2019)62 found that chimpanzees who experienced social withdrawal during infancy and juvenility, combined with severe abuse, were more likely to display higher levels of anxiety and dominance. In contrast, those who were mother-reared tended to exhibit lower dominance and restraint personality traits than hand-reared individuals. The use of wildlife by humans is not limited to laboratories and entertainment; practices like breeding and business are inadequately regulated in some regions of Southeast Asia.59 For example, the case of coconut-harvesting pig-tailed macaques, whose psychological well-being was assessed by Schowe and colleagues (2021)54 is emblematic. Having been deprived of social stimulation since infancy or juvenility, enrichment, sensory input, opportunities to exhibit species-typical behaviours, and a high-quality diet, these exploited macaques exhibited a mean welfare score of 4.8±1,2 out of 12 points, indicating an absence of positive mental states and high rates of abnormal behaviours and stereotypes, pointing to symptoms of compromised welfare.63\n\nFor all of that, the present research has one main objective and four secondary goals. Firstly, we assessed the effects of adverse experiences on socio-emotional and behavioural abilities of macaques victims of illegal trade. To achieve this, we studied social responsiveness, affiliative behaviours and grooming (as positive indicators of psychological well-being), abnormal and anxiety-like behaviours (as negative indicators of psychological well-being), and general welfare and personality traits of the resident macaques at Lao Conservation Trust for Wildlife centre (LCTW). LCTW, a former zoo converted into an animal rescue and rehabilitation centre. Currently, LCTW houses more than one hundred individuals from various species of macaques, which were victims of poaching. Secondly, we aimed to describe their socio-emotional and behavioural profile. Furthermore, we considered that the findings of this study may contribute to the understanding of (1) the proximate and (2) ultimate mechanisms involved in socio-emotional development in both human and non-human primates; and (3) to the design of more effective and efficient management and rehabilitation procedures for non-human primates in animal rescue and rehabilitation centres.\n\nBuilding on previous publications, we predicted that adverse and traumatic experiences including mother separation at early age, deprivation of social interactions, undesirable housing and humanisation, amongst others, may be linked to (1) social skills’ impairment in adulthood,21–31 (2) difficulties in coping with stress or a high expression of stereotypes and abnormal behaviour, indicators of negative welfare16,17,54,63 and (3) the development of certain personality traits related to neophobia, dominance or neuroticism.62\n\n\nMethods\n\nLao Conservation Trust for Wildlife (LCTW) operates in Lao PDR, a key corridor for the illegal trade in Southeast Asia, as a gateway between Thailand, Myanmar, Vietnam, Cambodia, and China. LCTW is registered by the Lao Government (under number 326/MoHA) and in the United Kingdom (under the number 1182501). Since 2018, this organisation has been engaged in the rescue, care, and release of native species victimised by illegal trade, currently providing shelter to over 400 animals across more than 26ha of land. Prior to this date, from 1994 to 2016, this centre was known as “Lao Zoo”, a place where visitors could interact and feed the resident animals, all of which were rescued from illegal trade. The majority of arrivals, both then and now, primarily consist of macaques rescued from the pet trade, where they were found in family settings, temples, or establishments like resorts. Regrettably, relevant information of the rescued macaques was missed between 1994 and 2017, which limits our knowledge of their life experiences. In order to link the background to a lack of social skills, a high expression of abnormal behaviour, a low score of welfare, and certain personality traits, we exclusively selected macaques with meticulously documented life experiences labelling them “focal” individuals. We collected data of abnormal and anxiety-like behaviours defined in the ethogram (Suppl. Tables 3-4 in the extended data), and we administered questionnaires (personality, welfare, social responsiveness) to these focal individuals only. Nonetheless, we gathered social behaviours for both focal and non-focal animals, as social interactions cannot be restricted to certain animals (Suppl. Table 5 in the extended data).\n\nWe thus focused on the study of 53 focal subjects within a broader sample of 88 macaques. Focal animals were ranged in ages between 1 and 18 years old (mean age ± SD = 8 ± 5 years) and were distributed across eleven groups/enclosures (Suppl. Table 1 in the extended data): P1 (651,56 m2) with 7 stump-tailed macaques (Macaca arctoides), consisting of 3 females and 4 males, with estimated ages ranging from 8 to 21 years old; P2 (653,76 m2) with 8 stump-tailed macaques, including 4 females and 4 males, ranging in age from 1 to 15 years old; P4 (949,77 m2) with 3 Rhesus (Macaca mulatta), 1 Assamese (Macaca assamensis) and 11 Northern pig-tailed macaques (Macaca leonina) [15 in total], of which 7 females and 8 males with estimated ages ranging from 1 to 11 years old; P5 (1236,63 m2) with 8 Rhesus, 9 Assamese, 1 pig-tailed and 1 long-tailed macaque (Macaca fascicularis) [19 in total], of which 9 females and 10 males with estimated ages ranging from 11 months to 11 years old; P6 (874,49 m2) with 3 Rhesus and 5 Assamese macaques [8 in total], comprising 4 females and 4 males with estimated ages ranging from 5 to 10 years old; P7 (705,08 m2) with 7 pig-tailed macaques, consisting of 4 females and 3 males with estimated ages ranging from 3 to 8 years old; P8 (340,04 m2) with 5 stump-tailed macaques of which 3 females and 2 males, with estimated ages ranging s from 10 months to 17 years old; P9 (233,03 m2) with 5 stump-tailed macaques, consisting of which 3 females and 2 males with estimated ages ranging from 5 to 8 years old; P10 (51,72 m2) with 2 Assamese, 3 long-tailed and 2 pig-tailed macaques [7 in total], comprising 3 females and 5 males with estimated ages ranging from 2 to 12 years old; BP1 (50-100 m2) with 3 pig-tailed macaques of which 1 female and two males with estimated ages ranging from 7 to 10 years old; and BP3 (50-100 m2) with 1 pig-tailed and 3 Assamese macaques [4 in total], consisting of 1 female and 3 males with estimated ages ranging from 10 to 13 years old.\n\nDuring the course of this research, the composition of macaque groups changed due to the frequent arrival of rescued individuals at the centre. Some of these new arrivals were initially housed separately and gradually introduced to the most compatible group. Others, following unsuccessful introductions, were relocated to quarantine, pending future attempts (see Suppl. Table 2 in the extended data for more details). All the enclosures, except for P10, BP1 and BP3 are naturalised, free ceiling spaces equipped with an electric fence, available wild trees, two holdings for introducing new members and addressing medical issues, a swimming pool, and platforms for the macaques. P10, on the other hand, is a sizable cage with a natural floor that includes platforms, enrichment to hide, four holdings and one swimming pool. The BP enclosures consist of three interconnected 50m2 cages (BP1, BP2 and BP3) that include a concrete floor, swimming pools and one platform each. Resident macaques in BP1 and BP3 share the middle cage BP2, enabling each group to use the additional space in rotational shifts every two days. There are no indoor facilities, and the animals remain outdoors with the whole group, except when necessary for specific reasons, such as medical interventions, cleaning, or repairs. As a consequence of the absence of indoor enclosures, keepers, and staff may enter the enclosures as needed, for tasks such as cleaning, maintenance, or medical procedures. Macaques are fed twice per day with seasonal vegetables, fruits, leaves and seeds, from 9:30 to 10:00 in the morning and from 15:00 to 15:30 in the afternoon.\n\nWe established several categories with the information collected on ZIMS (Zoological Information Management Software)64 or provided by oral testimonies from LCTW staff about the previous traumatic events of the subjects in order to study which type of early adverse experience or stressful history may impact dramatically on the development of SEB skills and personality of the subjects. The information gathered may be incomplete, ambiguous, or scarce, specially of those who arrived at the centre before 2018, which was obtained by former workers (ZIMS) and one-time keepers at Lao Zoo (oral testimonies). Ten categories were created, being three of them not related to the background: sex, current age, and species. Seven categories were referred to the subject’s background: origin, type of rearing, life experience, social exposure during infancy, social exposure during juvenility, mother separation before 14 months old, and age of arrival at the centre (for categories see Suppl. Table 1 in the extended data, for codes’ meaning and details see Table 1).\n\nWe combined two methods: questionnaires and behavioural observations. Socio-emotional and behavioural skills have been structured in five domains, following the BESSI [Behavioral, Emotional, and Social Skills Inventory]87 proposal, defined in Table 2. The present study has been focused on three of these domains: (1) social engagement, (2) cooperation, and (3) emotional resilience.\n\nWe collected behavioural data through observations,88 only while macaques had access to their outdoor enclosures, in other words, when they were not in the holding or hospital. Data on macaques’ behaviour was collected from November 14, 2022 to March 22, 2023 (for further information on the collected behaviours, see Suppl. Tables 3-5 in the extended data). We evenly distributed observation sessions of 20 minutes between 6:30 am and 17:00 pm on randomised days (Monday to Sunday). Each troop has been sampled for 12 ± 0.1 hours (min 11.67 hours, max 12.33 hours). Abnormal, anxiety-like, social (affiliative, sexual, agonistic and aggression-related) behaviours were recorded continuously with an all occurrences [multifocal] untimed-event strategy, whereas, the duration and frequency of grooming were recorded with a continuous [multifocal] timed-event strategy.89 The duration of grooming collected will not be used in the present study. For data collection, the observer (first author) used a Sony ICD-PX370 voice recorder in three enclosures (P4, P5, P9) and Zoomonitor software90 in eight enclosures (P1, P2, P6, P7, P8, P10, BP1, BP3), due to a variety of factors such as the lack of visibility, the number of individuals per group and the frequency of behaviours they exhibited. Following a bout recording strategy, we collected behaviours in bouts rather than the single repetition. For instance, in the case of repetitive and odd behaviours, we observed that “hit-self” or “self-bite” behaviours were seldom shown only once, but were performed in a set of repetitions or events. As an example, see Suppl. Video 1 in the extended data, in which an individual (Chock, P9) is exhibiting a “bout” that consists of: float limb, hit-self and self-bite amongst others, such as abnormal behaviours (e.g., self-pinch and abnormal displacement).\n\nThree human raters were carefully selected based on their substantial experience and significant time dedicated to working with the macaques. The first rater has spent more than four years continuously working with the macaques as a veterinarian and animal management. The second rater had an eight-month period of continuously working with the macaques as an enrichment coordinator. The third rater (first author) engaged with the macaques for a duration of six months, during which she collected the behavioural data for the present research (132 hours observation/total). Raters were explicitly instructed to refrain from discussing their assessments with other participants. We also provided comprehensive guidance on completing the three questionnaires, including discussions and clarifications on concepts associated with animal behaviour and welfare. Finally, we requested raters to respond according to their thoughts and current animal context.\n\nWe used the Social Responsiveness Scale (SRS), previously validated with adults91 and juvenile macaques,92,93 to evaluate social engagement and cooperation skills. The SRS [short version] scale comprise 14 items, which are associated with statements that need to be scored by a human rater (e.g., “Seems self-confident when interacting with others”) using a Likert rating scale between 1 and 5 (1 = not true 0%, 2 = sometimes true 25%, 3 = often true 50%, 4 = almost always true 75%, and 5 = always true 100%) As described by Balint and colleagues (2021),92 the scoring of the items 1, 5, 7 and 14 were reversed, so that higher scores reflected greater social deficiency for each item.\n\nWe employed the Animal Welfare Survey US [AWS]94 to evaluate the emotional and resilience skills domain. This questionnaire consists of 12 items, each one with a statement or a question that needs to be scored or replied by a human rater (e.g., “How often this individual display signs of positive welfare?”) in a Likert rating scale of 1 to 5 (e.g., 1 = never, 2 = rarely, 3 = occasionally, 4 = frequently, 5 = constantly). It includes positive and negative indicators of welfare and well-being, validated with Rhesus macaques, capuchins and chimpanzees95–97\n\nWe used an adaptation of Cattell’s 16 Personality Factors Questionnaire98,99 to assess the impacts of traumatic experiences on the development of personality. The questionnaire has been previously administered in chimpanzees62 and comprises 16 items, rated on a Likert scale 1–7. Each item was bipolar and the scores of raters described the subject evaluated closer to one pole or to the other.\n\n\nData analysis\n\nFrom the collected data, we calculated the frequency of each behaviour included in the ethogram per individual. Then, we calculated the rate89 for anxiety-like, abnormal and social behaviours (grooming, maternal care, other affiliative, other agonistic, social play and sexual behaviours) per subject based on frequency/observation time. For each group, we create matrices of directed dyadic grooming interactions.\n\nRank was calculated with the “EloRating” package100 in R,101 considering all dyadic agonistic interactions (dominance and submission) with a winner-loser outcome. Every macaque in each group was assigned a value between 0 (lowest ranking) and 1 (highest ranking).102\n\nFirst, we assessed the interrater reliability of the items of each questionnaire via intra-class correlation coefficients (ICC): ICC (3,1), to evaluate the reliability of individual ratings, and ICC (3,k), which indicates the reliability of mean ratings103 with JASP 0.17.3 software.104 To determine the social responsiveness, animal welfare and personality dimensions, we conducted an Exploratory Factor Analysis using a Robust Unweighted Least Squares (RULS) for factor extraction.105 We applied an orthogonal normalised Equamax rotation to generate uncorrelated factors.106,107 We based our analysis on polychoric correlations (adequate to Likert-scale ordinal data with asymmetric or with excess of kurtosis data) to achieve factor simplicity and determine factorial structure and goodness of fit.106–109 We calculated the correction for robust Chi-square with LOSEFER empirical correction.110 We considered factor loadings of the rotated loading matrix as significant when they were 0.5 or higher, in accordance with previous research.102,111 Finally, we determined the number of factors following two procedures. First, we applied the “latent root criterion” (i.e., eigenvalues above 1)92; and second, we used the optimal implementation of Parallel analysis based on minimum rank factor analysis.112 We assessed the robust goodness of fit using the root-mean-square error of approximation (RMSEA). We considered RMSEA values between.05 and.08 as fair.113 We conducted all the analysis using FACTOR 12.04.01.114\n\nWe computed unit-weighted factor scores for each individual, following the procedure described by Weiss and colleagues (2009).115 This calculation involved taking the mean of all the items with salient loadings (>0.5). Items with positive salient loadings were assigned a score of +1 and items with negative salient loadings were assigned a score of -1. Thus, the score for each individual within a particular factor represents the weighted average of that individual’s scores on all the items related to the factor.\n\nWe assessed the effect of each background-related category on the dependent variables or individual measures using generalised linear models (GLM). We created a total of 11 models, one per each individual measure. As dependent variables we used the rate of (1) social, (2) anxiety and (3) abnormal behaviours, (4) the rank, (5-6) the social responsiveness, (7-9) personality, and (10-11) welfare domains. We included as fixed factors in our full models (a) sex, (b) estimated current age, (c) origin (d) species and background [(e) rearing, (f) life experience, (g) infancy and (h) juvenile exposure, (i) mother separation, and (j) estimated age at the arrival).\n\nModel interference and the selection of the subsets of best models were performed using dredge function, which is based on the Akaike Information Criterion corrected for small sample sizes (AICc).116 From all models tested, we considered the best explanatory model per each dependent variable those with the lowest AICC or the highest ΔAICc compared to the full model containing all the predictor variables. To assess the collinearity, we examined the value of the variance inflation factor (VIF), with a model considered acceptable when the VIF < 5 between predictor variables. This analysis was conducted in R,101 where we performed GLMs using the “MuMln” package117 and related analysis, including VIF calculations using the “performance” package.118 Plots were generated using the “ggplot2” package.119 An alpha level of 0.05 was used as a cut-off for significance.\n\n\nResults\n\nWe divided the range of behaviours into 3 categories: social, abnormal and anxiety-like behaviours. We used the rates for anxiety-like, abnormal, and social behaviours (Suppl. Tables 6-11 in the extended data) to build the individual behavioural profiles.\n\nSocial behaviours include grooming interactions (both sender and receiver), social play (involving players regardless of whether they have started the game), other affiliative behaviours such as initiating contact (e.g., eye gaze, touch, following) or reciprocal affiliation (embrace, mutual teeth chattering, mutual touch), other agonistic behaviours (e.g., consolation, requesting/giving support), maternal care for behaviours directed towards unweaned infants, and socio-sexual behaviours for initiators only (Suppl. Table 7 in the extended data). Within social behaviours, it is noteworthy from our results that other agonistic behaviours such as appeasement or consolation, social play, and socio-sexual behaviours were observed at the lowest frequency in the majority of the enclosures, with social play being absent in P1 and P9, and socio-sexual in P6 (Suppl. Table 11 in the extended data). Only two groups exhibited a high rate of social play: P4, which had the highest number of infants and juveniles, and P10. No group exhibited a high rate of sexual behaviours (Suppl. Table 11 in the extended data). Maternal care was naturally observed only in those groups with unweaned infants (P8 and P5).\n\nThe anxiety-like category consists of four behaviours: genital self-inspection (including masturbation), scratching/rubbing, others self-directed behaviours, and yawning (Suppl. Table 8 in the extended data). As part of our predictions, we expected to find a high rate of anxiety-like behaviours in all groups. Indeed, our results show that not only was the rate of anxiety-like behaviours high, but also these behaviours were predominant over social and abnormal behaviours in the vast majority of the enclosures (Suppl. Table 10 in the extended data).\n\nAbnormal behaviours were divided into six subcategories due to the wide range of such behaviours included in the ethogram. These subcategories comprised self-directed behaviours (e.g., poke body, grooming stereotypically, self-suck), postural (limited to leg-lift), self-abuse (e.g., self-bite, hit-self, trichotillomania), kinetic (e.g., float limb, pacing, twist), oral (e.g., regurgitation, reingestion, pica), and miscellaneous (e.g., touch urine stream, other abnormal behaviour not included in the ethogram) (Suppl. Table 9 in the extended data). Our findings reveal that the rate of abnormal behaviours was notably high in several groups, being higher than social behaviours in BP3, and slightly lower in P9 and P7 (Suppl. Table 11 in the extended data). All the groups exhibited abnormal behaviour, with the lowest rate observed in P4, which is again the group with more infants and juveniles who therefore arrived at the centre at an early age (Suppl. Table 11 in the extended data).\n\nThe reliability of individual ratings (3,1) ranged from 0.29 (Species typical reaction) to 0.76 (Socially tense) with a general mean of 0.52. The reliability of mean ratings (3, k) for the traits ranged from 0.55 (Species typical reaction) to 0.92 (Socially tense) with a mean of 0.75. There were no items with zero or negative values. The inter-rater reliabilities of all 14 items are presented in Table 3.\n\na Reverse items. 53 subjects and 3 raters/measurements, ICC type as referenced by Shrout & Fleiss (1979).\n\nBased on the normed MSA (Measure of Sampling Adequacy) all the items obtained values above 0.5, indicating its adequacy in representing the underlying constructs (Table 4). Therefore, we retained all the items in the exploratory factor analysis. Based on the latent root criterion, we identified 2 factors to retain (Table 6). The two factors accounted for 73.66% of the variance (Table 5). According to the RULS, the value of the Kaiser-Meyer-Olkin (KMO) test was 0.66 (mediocre) [CI 0.364, 0.561] and Bartlett’s Test of Sphericity was significant (B=1755.7; df=91, p<0.001), thus indicating the adequacy of the correlation matrix. RMSEA fit was fair (0.078; [Bootstrap 95% CI 0.055, 0.068]).\n\nAccording to the latent root criterion and an adequacy load of 0.5, two factors were loaded with the majority of the 14 items (Table 6). We interpreted the load of reverse items (1, 5, 7 and 14) on the factors as negative. Five items positively loaded on the first factor (F1): Socially tense (0.902), Social avoidance (0.875), (Not) Eye contact (0.760), Socially awkward (0.694), and Lonely (0.575). Furthermore, three reverse items scored negatively on this factor, Socially confident (0.885), Playful (0.701), and Communication skills (0.646). This factor was denominated as Social Reluctance. The second factor was labelled as Inappropriate Behaviour, scoring positively with seven items: Bizarre behaviour (0.825), Stereotypes (0.804), Restricted interests (0.784), Stares into space (0.774), Socially awkward (0.691), No physical coordinated (0.656), (Not) Eye contact (0.553); and negatively with Species typical reaction (0.787) and Communication skills (0.627).\n\nThe reliability of individual ratings (3,1) ranged from 0.29 (Control of physical environment) to 0.68 (Number of relationships’ satisfaction) with a general mean of 0.47. The reliability of mean ratings (3, k) for the traits ranged from 0.55 (Control of physical environment) to 0.87 (Number of relationships’ satisfaction) with a mean of 0.72. There were no items with zero or negative values. The inter-rater reliabilities of all 12 items are presented in Table 7.\n\nBased on the normed MSA (Measure of Sampling Adequacy), all the items obtained values above 0.5 indicating its adequacy in representing the underlying constructs (Table 8). Based on the latent root criterion, we identified 2 factors to retain (Table 10). The two factors accounted for 76.65% of the variance (Table 9). According to the RULS, the value of the Kaiser-Meyer-Olkin (KMO) test was 0.91 (very good) [CI 0.596, 1.200] and Bartlett’s Test of Sphericity was significant (B=1763.4; df=66, p<0.001), thus indicating the adequacy of the correlation matrix. RMSEA fit was close (0.03; [Bootstrap 95% CI 0.049, 0.062]).\n\nAccording to the latent root criterion and an adequacy load of 0.5, two factors were loaded with the majority of the 12 items (Table 10). One single item was loaded in the first factor (F1) Psychological stimulation (0.785); therefore, we labelled this factor Psychological Stimulation. The second factor was positively related to Cope with the stress (0.919), Impact of experiences (0.820), Balance of the experiences (0.707), Control of physical environment (0.560) and Physical health (0.544), and negatively with Negative welfare indicators (-0.886) and Stress frequency (-0.834); and this factor was named Welfare.\n\nThe reliability of individual ratings (3,1) ranged from 0.005 (Sensitivity/Objectivity) to 0.61 (Social boldness/Shyness) with a general mean of 0.37. The reliability of mean ratings (3, k) for the traits ranged from 0.015 (Sensitivity/Objectivity) to 0.92 (Social boldness/Shyness) with a mean of 0.59. There were no items with zero or negative values. The inter-rater reliabilities of all 16 items are presented in Table 11.\n\nBased on the normed MSA (Measure of Sampling Adequacy) three of the items (Sensitivity/Objectivity, Abstractedness/Pragmatism and Perfectionism/Flexibility) obtained values below 0.5 suggesting that they correlated with other items and failing its adequacy in representing the underlying constructs (Table 12). Thus, we excluded these items during the exploratory factor analysis. In the second round, all the MSA values were above 0.5 (Table 12). Based on the latent root criterion, we identified 3 factors to retain (Table 13). The three factors accounted for 76.55% of the variance. According to the RULS, the value of the Kaiser-Meyer-Olkin (KMO) test was 0.833 (good) [CI 0.362, 0.862] and Bartlett’s Test of Sphericity was significant (B=1771.1; df=78, p<0.001), thus indicating the adequacy of the correlation matrix. RMSEA fit was mediocre (0.087; [Bootstrap 95% CI 0.055, 0.073]).\n\nAccording to the latent root criterion and an adequacy load of 0.5, three factors were loaded with the majority of the 16 items (Table 14). Items were previously defined by two adjectives, first one corresponding to the lowest score (1) and second one the highest score (7). We selected the second adjective to label the obtained factors. On the first factor (F1), the items that positively loaded were Pragmatism (0.809), Apathy (0.736) and Conventionalism (0.675), and those that negatively loaded were Unruliness (-0.751) and Openness (-0.610). Thus, we labelled this factor as Introversion. On the second factor (F2), the items positively loading were Self-assurance (0.683), Carelessness (0.563), and Openness (0.529) and the items negatively loading were Flexibility (-0.671) and Shyness (-0.589), thus we named this factor Calmness. Finally, the last factor was related to Detachment (0.792), Cooperation (0.598), Conventionalism (0.587), Emotional unsteadiness (0.559) and Shyness (0.538), and negatively with Affiliation (-0.707), Carelessness (-0.562) and Self-assurance (-0.526); Therefore, this factor was named Unfriendliness.\n\nTwo of the initial categories had to be removed from the analysis, due to the lack of variability amongst the sample: Mother separation (97% of the subjects were separated from their mothers and only 3% were not) and Origin (97% of the subjects were born in the wild, 3% were captive conceived). In the same line, c3 category (Species-Macaca fascicularis) was only represented by two subjects, which was not enough data to perform a generalised linear analysis. Therefore, we had to exclude the long-tailed macaques from the GLM analysis, although the description of their socio-behavioural profile is still included in this study (Suppl. Table 6-11 in the extended data). Tables 15 and 16 contain the comparison between the best explanatory model and the full model per each response variable, significant ones being in bold. The “Best Model” was selected according to the lowest AICc.120,121 The collinearity between the predictors for those best models that seem to be influenced by two variables or more is less than 5 in all cases. Tables 17 and 18 show the best explanatory model per measure, significant predictive variables being in bold.\n\nFor each model and predictor, estimates, standard errors (SE), t value, and p -values (p).\n\nFor each model and predictor, estimates, standard errors (SE), t value, and p -values (p).\n\nRegarding GLM analysis results for the observed behaviours, the best model that predicts the rate of social behaviours includes Juvenile Social Exposure and Sex, only the first one being significant (Table 17). As shown in Table 1, the lowest value of this category (h1) corresponds to “Accompanied” whereas, h3 and h4 mean “Alone” and “Unknown” respectively. The direction of the prediction is inverse for h3, therefore subjects who spent their juvenility alone may be less social in the near or later future than those that were accompanied (Figure 1). Pairwise contrasts of the significant category revealed that h3 or “Alone” subcategory is the predictive variable for lower display of social behaviour (h1-h3 p-value = 0.05; h2-h3 p-value = 0.04). The anxiety-like best model includes Estimated Age at Arrival, Species and Sex (Table 17). According to this model, the later an individual arrives at the centre (j3), the higher the rate of anxiety behaviours will exhibit (estimate = 0.60) (Figure 2) (j2-j3 pairwise contrast: p-value = 0.04, estimate = -0.963), males (a1) being more likely to be anxious than females (a2). In addition, the rate of anxiety-like behaviours seems to be significantly lower in rhesus (c5) or pig-tailed macaques(c4) than in stump-tailed (c1), with pairwise contrast being significant in c1-c5 (p-value = 0.003) and c1-c4 (p-value = 0.006) (Table 17). Third, the best model that predicts the rate of abnormal behaviours consists of Rearing and Sex (Table 17), with Rearing predictor being the only significant. The direction of e2 predictor’s influence is positive, meaning that macaques that were raised by humans are more likely to exhibit abnormal behaviour than those that were raised by their own parents or by foster parents (Figure 3). Lastly, Sex is the significant parameter that may predict the acquisition of the rank in the hierarchy (Table 17). The direction of the influence is negative for a2, meaning that males are more likely to hold a higher rank.\n\nInfluence of Juvenile Social Exposure on the rate of social behaviours (Best model 1), influence of Estimated Age at Arrival on the rate of anxiety-like behaviours (Best model 2), and influence of Rearing on the rate of abnormal behaviours (Best model 3). Black inverse triangles represent outliers. For definition of the codes see Table 1.\n\nIn relation to the predictive models for the results of the questionnaires, Juvenile Social Exposure is the significant variable that seems to predict the first social responsiveness domain, Social Reluctance (Figure 4), whereas, Rearing is the predictor for the second domain, Inappropriate Behaviour (Table 18). Best model 5 consists of Juvenile Social Exposure only, the direction of the influence being positive with h3 and pairwise contrasts being significant for h1-h3 (p-value=0.003) and h2-h3 (p-value=0.03) Therefore, social withdrawal during juvenility may result in higher Social Reluctance in the near or later future. Best model 6 involves Rearing only, with e2 or hand-rearing being the significant variable to predict a higher item score for Inappropriate Behaviour (Figure 5). Regarding personality questionnaires, we obtained three significant predictive models corresponding to the three personality resulting domains from Cattell 16PF questionnaire (Table 18). The best explanatory model for Introversion includes Juvenile Social Exposure, Life Experience, Sex and Species. According to GLM results, subcategories f2 (macaques used for human entertainment), f4 (macaques that were rescued from the trade whose past is not exhaustively known), and a2 (females) positively influence this domain (Figure 6). In contrast, subcategories h4 (unknown juvenile social exposure) and c2 (Assamese macaques) negatively predict this domain, meaning that Assamese tends to be less introverted than the rest of studied species (Figure 7). However, pairwise contrast shows that within Juvenile Social Exposure, h3 is also a predictive subcategory for lower introversion (h2-h3 estimation=-5.15, p-value=0.007), only f4 would be a significant predictor for this variable (f1-f4 p-value=0.02; f3-f4 p-value=0.04), and any pairwise contrast is significant for Species category. Best Model8, that may predict Unfriendliness, consists of Rearing (e2) whose estimation is positive, meaning that hand-rearing predicts higher item score for this domain (Figure 8). In contrast, e2 or hand-rearing is the only significant variable that negatively predicts the last personality domain, Calmness (Table 18 and Figure 9). Regarding the last questionnaire, the best model to predict the Welfare domain consists of Rearing (Best model 10), the influence of e2 predictor being negative for welfare score (Table 18 and Figure 10). Finally, Best model 11 involves Infancy Social Exposure and Life Experience predictors. Subcategory g3 seems to negatively influence the Psychological Stimulation domain, thus macaques that spent their infancy alone are more likely to be rated lower in welfare than those that were accompanied (g1-g3 p-value = 0.03) (Table 18) (Figure 11). Moreover, macaques used for entertainment (f2) and trade (f4) seem to be predictive of the item score for this domain as well (Figure 12). Nevertheless, pairwise contrast revealed that only f1-f4 comparison is significant at p-value = 0.02 with estimate = 1.276.\n\nInfluence of Juvenile Social Exposure on Social Reluctance domain (Best model 5) and influence of Rearing on Inappropriate Behaviours domain (Best model 6). Black inverse triangles represent outliers. For definition of the codes see Table 1.\n\nInfluence of Juvenile Social Exposure and Life Experience on Introversion domain (Best model 7) and influence of Rearing on Unfriendliness (Best model 8) and Calmness (Best model 9) domains. Black inverse triangles represent outliers. For definition of the codes see Table 1.\n\nInfluence of Rearing on Welfare domain (Best model 10), and influence of Infancy Social Exposure and Life Experience on Psychological Stimulation domain (Best model 11). Black inverse triangles represent outliers. For definition of the codes see Table 1.\n\n\nDiscussion\n\nThe primary objective of this study was to assess the impact of illegal trade on socio-emotional and behavioural skills,21 psychological welfare61–63 and personality traits62 in former abused macaques. We employed the BESSI framework to describe the influence of our predictor variables on three of the five domains included in this inventory: social engagement, cooperation, and emotional resistance skills.\n\nFirstly, we expected to find socio-behavioural deficiencies in our focal subjects, including reduced play, socio-sexual impairment, lower rank,22–27 and a reduced repertoire of species-typical behaviours.28 As detailed in Suppl. Table 6 in the extended data and Table 11, sexual behaviours were rarely exhibited across all enclosures, and social play was predominantly observed in only two groups, as expected. The least exhibited behaviour was “other agonistic” in several groups, which includes the behaviours such as appeasement, giving/asking for support, reconciliation, and consolation. It is worth stressing that we included these behaviours in the “Rate of Social behaviours” category because we considered them to be post-conflict affiliation behaviours, that could be displayed by either the victim or the aggressor.122 Identifying this range of behaviours was challenging due to their species-typical nature and their diversity, and the existence of consolation in macaques is still under debate.123 Thus, we cannot conclusively determine whether agonistic behaviours were genuinely less frequent or if some of them were overlooked during the observation sessions.\n\nAccording to our GLM analysis findings, the rate of social behaviours is significantly influenced by Juvenile Social Exposure (Table 17). Macaques who experienced social isolation during juvenile years appear to exhibit less social behaviour. Similarly, the social responsiveness domain “Social Reluctance” is influenced by the social withdrawal during juvenility (Table 18). This domain includes avoidance of social interactions, a lack of social self-confidence, diminished playful interest, and communication skills. Therefore, these results suggest a link between social impairment and social anxiety and the deprivation of social stimulation during the critical period from 14 months to 36 months of age in macaques. For decades, early adverse experiences, such as mother deprivation or infant isolation, have been considered crucial for the development of social skills in non-human primates.33 Our results do not contradict these established facts; instead, they highlight the significance of social stimulation during later developmental stages in shaping social skills, especially in the realms of cooperation (social warmth) and social engagement skills (sociability). Additionally, multiple studies have stressed the critical role of the mother and peers during pre-adolescence in shaping the behavioural profile of primates.124 Likewise, our findings indicate that the Inappropriate Behaviours domain seems to be influenced by the Rearing category, mirroring the predictor models for Welfare and the rate of abnormal behaviours.6 This social responsiveness domain comprises bizarre behaviours and stereotypes amongst other non-typical behaviours of these species. Moreover, it includes items related to communication skills and physical coordination deficiencies. In substance, a high score in this domain means that an individual displays oddly in a social context, closely associated with abnormal behaviour and social anxiety, and indicative of compromised welfare.63\n\nRegarding rank, we did not observe any significant effects related to the background, as predicted. The significant factor that appeared to influence the rank was “Sex”, probably due to the male-dominant nature of the studied macaque species. Bastian and colleagues22 revealed that absence of adults and limited social interactions during early life negatively affect the acquisition of dominance rank, along with age and sex. We suggest that our results differ from previous studies due to the limited background variability in our sample. In the study conducted by Bastian and colleagues, there were three distinct groups with different rearing backgrounds. In contrast, the majority of our subjects have experienced traumatic pasts, and as a result, the predictive strength of the different “background” variables may be significantly lower compared to the influence of Sex.\n\nSecondly, we predicted to find, amongst our sample, psychological distress based on higher rate of anxiety-like behaviours and/or higher expression of abnormal behaviour and stereotypes.1,2,37,38 While the rate of anxiety is notably high across all enclosures, as predicted, our results reveal that the rate of anxiety-behaviours appear to be significantly influenced by the Estimated Age at Arrival, Sex, and Species only (Table 18). In contrast to previous studies in macaques, bonobos, capuchins, and chimpanzees,62,125–127, our findings indicate that males are more likely to exhibit anxiety-like behaviours compared to females. According to our findings, the manifestation of anxiety-like behaviours may vary amongst different species. Despite that the best explanatory model for abnormal behaviours does not include Species category, the rate of both behaviours seems to be significantly lower in Rhesus and pig-tailed compared to stump-tailed or Assamese. This lends support to the idea that using a single species as a model for abnormal or anxiety behaviour within the Macaca genus may not be advisable.128\n\nContrary to our predictions, the social exposure in infancy or juvenility do not appear to predict anxiety in our sample, as reported in other NHP.3 Nonetheless, the j3 subcategory or arriving at the centre in adulthood seems to be significant to predict a higher rate of anxiety. Given that individuals arriving at the centre in later life or adulthood might have spent more time in the illegal trade, we interpreted that the longer an individual has been a victim of the illegal trade, the higher the rate of anxiety behaviours, regardless of the life experience or other conditions. Therefore, we claim that the set of potential distressing events associated with illegal trade, such as exposure to humans, social deprivation, or psychological abuse, have a discernible impact on behavioural outcomes. In essence, elevated levels of anxiety are considerably more prevalent in those macaques who experienced episodes of distress over extended periods, with the absence of peer interactions during juvenility being particularly pivotal for the development of social anxiety.\n\nRegarding the results of the Welfare questionnaire, we named the first domain as “Welfare” because the items that positively loaded on this factor were indicative of preserved welfare, such as “good physical health” and “coping well with the stress”, while those with negative loadings were associated with compromised welfare, such as “high stress frequency”. This is consistent with the traditional use of abnormal behaviour and stereotypes as predictive factors of negative welfare as outlined by Mason and colleagues.63 Several studies have highlighted the profound impact of rearing conditions on the development of behavioural profiles in laboratory macaques, particularly the exhibition of odd repetitive behaviours or stereotypes.12,13,16,17,21,27,28 The best explanatory model for predicting the rate of abnormal behaviours in our sample includes the type of rearing, which aligns with previous findings. In addition, this parameter is also included in the best predictor model for Welfare, as observed in the Inappropriate Behaviour domain. Consequently, hand-rearing conditions emerge as a risk factor for an individual’s inability to cope with stress in social and non-social events, with the resulting detriment to welfare. Since most victims of the illegal trade are separated from their mothers at an early age and reared by humans for purposes such as keeping them as pets or exploiting them for economic purposes, it may be challenging to prevent hand-rearing practices in these circumstances. Nonetheless, rescue centres that frequently receive unweaned rescued primates should consider the possibility of finding foster parents to rear these infants instead of opting for hand-rearing. Similarly, zoos that occasionally care for neglected newborns should contemplate fostering as an alternative to evade the potential effects of hand-rearing or, at the very least, employ both methods to minimise its impact.\n\nFinally, the Psychological Stimulation domain seems to be negatively influenced by the lack of social exposure during infancy and the type of life experiences. EFA analysis revealed that Psychological Stimulation, represented by the item 5 of the Animal Survey Welfare questionnaire, constituted a domain in itself (Table 10), suggesting the critical role of psychosocial enrichment in determining welfare in our sample. This item could be rated from “very bored” (1) to “very stimulated” (5), with a higher score indicating positive welfare. Individuals raised in social isolation during infancy for recreational purposes tend to be rated lower in this domain, regardless of the quality of the enrichment. This finding denotes that past experiences can diminish engagement skills of macaques with their environment. Ideally, the past life of the resident animals at zoos and rescue centres should be considered when designing high-quality enrichment protocols to guarantee their welfare.\n\nThirdly, we introduced Cattell’s 16PF questionnaire for the first time in macaques, which had previously been validated in humans and chimpanzees.62,98,99 We identified three personality domains: the first domain, which we labelled as “Introversion”, showed a positive relationship with pragmatism and apathy, and a negative relationship with openness. The second domain, named “Calmness”, was associated with items opposing vigilance and apprehension. The third factor was designated “Unfriendliness” as it displayed an inverse relationship with affiliation, carelessness and self-assurance. On one hand, we expected to find similar personality traits to those in the reference study, due to the similarity of the backgrounds, despite being different species. We obtained two opposite and comparable domains (Introversion-Extraversion, Calmness-Anxiety) and one non-related (Unfriendliness) to any of the factors described by Ortin and colleagues.62 Nevertheless, the resulting domains are comparable to those defined by Weiss and colleagues in Rhesus macaques: Dominance, Confidence, Openness (Introversion in our results), Anxiety (Calmness in our results), and Friendliness (Unfriendliness in our results).129 On the other hand, we predicted that the personality profiles may be impacted by, at least, one of our background categories, as occurred in the baseline study.62 GLM analysis shows that the Introversion factor seems to be impacted by several predictive variables which were both related (Juvenile Social Exposure and Life Experience) and not related to the background (Sex and Species) (Table 18). Regarding Sex, females tend to be more introverted than males, which aligns with macaques’ social structure, where males have to leave their natal group and socialise to be integrated in other groups, while females typically remain in their original group.130 Regarding Species, it is worth recalling that most of the groups are mixed-species, except for P1, P2, P8, P9 (stump-tailed only) and BP1 (three pig-tailed only). Because of that, we cannot be certain whether this influence is accurate or caused by the unequal composition of the group. Furthermore, pairwise contrast reveals that the difference between species is not significant enough to predict the introversion trait in individuals. We suggest conducting additional research to thoroughly investigate macaque personality at the species-level. The variables related to the background that predict Introversion are j4 or unknown juvenile social exposure, f2 or entertainment life history and f4 or unknown past in illegal trade. At first sight, we could only take into account f2, which means that those macaques that were used or exploited for human entertainment are more likely to be introverted than those that were pets or born in the zoo. Nevertheless, those individuals who were raised in social isolation during juvenility are more likely to be introverted than those who were accompanied, according to the pairwise contrast analysis. We consider these significant results to be in line with our reference study in terms of a reduced social interaction in early life shapes extroversion-introversion traits in individuals.62 Finally, the best explanatory models for both Calmness and Unfriendliness domains are predicted by the same subcategory, e2, in opposite directions: hand-rearing individuals are more prone to be more anxious and unfriendly or less calm and friendly. We assert that individuals’ anxiety levels and social warmth may also be related to early mother separation and high exposure to humans in early life as this is what being hand-reared implies.61,62 These findings are consistent with previous research in NHP.3,6,20,21,42,48,131\n\nConsequently, the personality structure of the study sample seems to be shaped by the adverse past according to our results. Our results show potential for the use of Cattell’s 16PF for the assessment of personality in macaques. Nonetheless, as shown in Table 11, three of the items (Sensitivity-Objectivity, Abstractedness-Pragmatism and Perfectionism-Flexibility) obtained ICC 3,k values below 0.5, which indicates poor reliability. Whilst we obtained significant results consistent with our predictions, raters agreed with (1) the complexity of the adjectives to describe the personality traits of the focal macaques, (2) the need to have a deeper understanding of the focal subjects and (3) macaque behaviour to fill the questionnaires. Therefore, further studies on the use of Cattell’s 16PF questionnaire in personality assessment should be conducted to evaluate its suitability in macaques. We also suggest using a simpler and shorter questionnaire validated in Macaca fuscata132 or commonly implemented and validated questionnaires in macaques as the Hominoid Personality Questionnaire.129\n\nOverall, these results would be in concordance with (1) the baseline study of Lopresti-Goodman in rescue chimpanzees,61 which states that victims of the wildlife trade tend to exhibit psychological distress and more stereotype; (2) former research in bushmeat chimpanzees,62 which states that traumatic past predicts higher anxiety in the victims, and (3) in exploited macaques (Macaca leonina),54 which states that stressful episodes related to the use and abuse of macaques for economic profits leads to their detrimental welfare.\n\n\nConclusion\n\nIn conclusion, we have determined that early adverse experiences related to illegal trade exert a significant and lasting impact on the development of social, emotional, and behavioural skills, as well as personality traits in Macaca arctoides, Macaca assamensis, Macaca leonina and Macaca mulatta. Notably, the absence of social stimulation during the juvenile phase (14-36 months) predicts a reduced rate of social behaviours, increased social avoidance in both early and later life, and higher levels of introversion. Hand-rearing also plays a pivotal role in shaping sociability and social warmth, serving as a strong predictor for the exhibition of inappropriate behaviours in social contexts. Furthermore, being raised by humans impacts the development of resistance to stress and emotional resilience skills, correlating with a higher rate of abnormal behaviour and compromised welfare. Additionally, hand-rearing seems to significantly influence personality traits, especially leading to elevated scores in unfriendliness and anxiety. The use of macaques for human entertainment emerges as the life experience that most profoundly affects the welfare score and the manifestation of introversion traits. Finally, macaques deprived of social exposure during infancy tend to exhibit lower skills of social and environmental engagement, contributing to detrimental welfare.\n\nWe propose three avenues for future research (1) further comparative studies to clarify the differences between diametrically opposite backgrounds (e.g., laboratory macaques versus former pet macaques versus species-typical rearing macaques), and their impacts on behavioural, emotional and social skills; (2) additional research into the application and effectiveness of Cattell’s 16PF questionnaire in macaques; and (3) more pragmatic studies on primates who were victims of illegal trade.\n\nAs a future prospect, we hope that this and further studies on whether prolonged traumatic experiences impact on socio-emotional and behavioural skills, may serve to the conservationist struggle against illegal trade. For instance, proving the severe repercussions of trafficking on primates could contribute to the strengthening of laws and policies aimed at wildlife protection, while simultaneously bolstering penalties and fostering public education to discourage this practice.\n\n\nAuthor contributions\n\nAR: Conceptualization, data curation, formal analysis, investigation, methodology, software, visualisation, writing—original draft preparation; MP: Formal analysis, methodology, supervision, writing—review & editing; ML: Conceptualization, formal analysis, methodology, project administration, resources, supervision, writing—review & editing.\n\n\nEthics statement\n\nThe study was based purely on observational data without any invasive interventions. It was conducted in accordance with all national and institutional guidelines for the care and management of primates as established by each of the collaborating institutions, Association for the Study of Animal Behaviour/Animal Behavior Society and the Spanish Government (RD/53/2013).",
"appendix": "Data availability\n\nOSF: Impacts of illegal trade on socio-emotional and behavioural skills in macaques, https://doi.org/10.17605/OSF.IO/RZVMY. 133\n\nThe project contains the following underlying data:\n\n- Influence of background GLM Models.R\n\n- Rawdata-Rdatabase.xlsx\n\nOSF: Impacts of illegal trade on socio-emotional and behavioural skills in macaques, https://doi.org/10.17605/OSF.IO/RZVMY. 133\n\nThis project contains the following extended data:\n\n• Supplementary Table 1.docx (Biographic information of focal subjects).\n\n• Supplementary Table 2.docx (Group composition’s change during the observation period).\n\n• Supplementary Table 3.docx (Catalogue of abnormal behaviours).\n\n• Supplementary Table 4.docx (Catalogue of anxiety-like behaviours).\n\n• Supplementary Table 5.docx (Catalogue of social behaviours).\n\n• Supplementary Table 6.docx (Rate for social, abnormal and anxiety-like behaviours).\n\n• Supplementary Table 7.docx (Rate for grooming interaction and social behaviours: maternal care, other affiliative, other agonistic, social play and socio-sexual).\n\n• Supplementary Table 8.docx (Rate for anxiety-like behaviours: genial self-inspection, other self-directed, scratching/rubbing, self-groom and yawning).\n\n• Supplementary Table 9.docx (Rate for abnormal behaviours).\n\n• Supplementary Table 10.docx (Average rate of observed behaviours (social, abnormal, anxiety-like) per enclosure).\n\n• Supplementary Table 11.docx (Average rate of observed social behaviours per enclosure).\n\n• Supplementary Video. mp4 (Example of a sequence of several bouts of abnormal behaviour).\n\nData are available under the terms of the Creative Commons CC BY Attribution 4.0 International (CC-BY 4.0).\n\n\nAcknowledgments\n\nFirstly, we thank the LCTW staff who completed the SRS, welfare and personality questionnaires. We would also like to thank the macaque team, Vuethao Vangkou, Somkit Phonexaiya and Melody Bomon for their commitment in gathering information about the background of the resident macaques, their help being essential for the present study. Thank Dr Jasmine V Ware for your constant support and advice, regarding questionnaires and data analysis. Last but not least, we express our gratitude to the Lao Conservation Trust for Wildlife centre and its director Jeremy Phannah for hosting this project.\n\n\nReferences\n\nColeman K, Pierre PJ: Assessing anxiety in nonhuman primates. ILAR J. 2014; 55(2): 333–346. Publisher Full Text\n\nKalin NH, Sheltona SE: Nonhuman primate models to study anxiety, emotion regulation, and psychopathology. Ann. N. Y. Acad. Sci. 2003; 1008(1): 189–200. Publisher Full Text\n\nWorlein JM: Nonhuman primate models of depression: Effects of early experience and stress. ILAR J. 2014; 55(2): 259–273. 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The IUCN Red List of Threatened Species 2020. 2020; e.T12549A17950189. Publisher Full Text\n\nNegrín AR, Fuentes AC, Espinosa DC, et al.: The loss of behavioral diversity as a consequence of anthropogenic habitat disturbance: the social interactions of black howler monkeys. Primates. 2016; 57(1): 9–15. PubMed Abstract | Publisher Full Text\n\nLenzi C, Speiran S, Grasso C: “Let me take a selfie”: Implications of social media for public perceptions of wild animals. Soc. Anim. 2020; 18(1): 1–20. Publisher Full Text\n\nOECD: The Illegal Wildlife Trade in Southeast Asia: Institutional Capacities in Indonesia, Singapore, Thailand and Viet Nam. Paris: Illicit Trade, OECD Publishing; 2019. Publisher Full Text\n\nBanjade M, Adhikari P, Hong-Shik O: Illegal wildlife trade in local markets of Feuang and Mad districts of Vientiane Province, Lao People’s Democratic Republic. J. Asia. Pac. Biodivers. 2020; 13(4); 511–517. 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}
|
[
{
"id": "294419",
"date": "28 Jun 2024",
"name": "Luciana Oklander",
"expertise": [
"Reviewer Expertise Behavior",
"genetics",
"ecology and conservation of primates"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is an exceptional work; it contributes a lot to science and knowledge and above all it is novel in terms of approach and very necessary. All of us who work or are in contact with rescue centers know that animals that have been pets are very difficult (or impossible) to rehabilitate in order to be parte of a serious reintroduction or population reinforcement project, but this knowledge was not supported to my knowledge, until now by scientific studies. It was also a saying that the younger you rescue them, the more possibilities to rehab, but this study scientifically demonstrates it.\nHowever, it seems to me that the manuscript would need some adjustments in the abstract so it is understood precisely how the work was carried out. On the results a strong reduction of the text and of the tables presented is needed, making them more understandable for any reader in the form of graphs or histograms.\nAbstract\nAdd that 53 focal subjects were studied within the resident macaques at Lao Conservation Trust for Wildlife center (LCTW). LCTW, a former zoo converted into an animal rescue and rehabilitation centre.\nWhen you mention social exposure, say that you are referring to individuals of the same species (if that is the case).\n“The lack of juvenile social contact predicts reduced social behaviours and an inclination towards social avoidance in adulthood. Macaques raised by humans tend to exhibit more abnormal behaviours in social contexts, compromising their welfare. Deprivation of social exposure in infancy negatively impacts psychological stimulation and overall welfare. The duration of time spent in illegal trade correlates with heightened anxiety levels. Personality traits such as ‘Calmness’ and ‘Unfriendliness’ are influenced by rearing conditions, with macaques deprived of social interaction during their early years showing higher levels of introversion. In conclusion, the absence of social exposure during early life and hand-rearing due to illegal trade significantly shape”\nAll of this could be summarized in a paragraph that makes it clear that the more human contact and the less with their own kind, anxiety levels intensify, etc., as is very well written in the conclusions.\nIntroduction\nadverse childhood experiences (ACE) early adverse rearing experiences (EARE), what is the difference between these?\nsocio-emotional and behavioural (SEB). please mention this without the acronyms\n“and four secondary goals” wich ones?\n“deprivation of social interactions”, always clarify with individuals of the same species\n\nMethods\n“Focal animals were ranged in ages between 1 and 18 years old.” Add here what the ages of infant/adolescent and adult are in each of these species.\n“Focal animals were ranged in ages between 1 and 18 years old (mean age _ SD = 8 _ 5 years) and were distributed across eleven groups/enclosures(Suppl. Table 1 in the extended data): P1 (651,56 m2) with 7 stump-tailed macaques (Macaca arctoides), consisting of 3 females and 4 males, with estimated ages ranging from 8 to 21 years old; P2 (653,76m2) with 8 stump-tailed macaques,including 4 females and 4 males, ranging in age from 1 to 15 years old; P4 (949,77 m2) with 3 Rhesus (Macaca mulatta),1 Assamese (Macaca assamensis) and 11 Northern pig-tailed macaques (Macaca leonina) [15 in total], of which7 females and 8 males with estimated ages ranging from 1 to 11 years old; P5 (1236,63 m2) with 8 Rhesus, 9 Assamese,1 pig-tailed and 1 long-tailed macaque (Macaca fascicularis) [19 in total], of which 9 females and 10 males withestimated ages ranging from 11 months to 11 years old; P6 (874,49 m2) with 3 Rhesus and 5 Assamese macaques [8 intotal], comprising 4 females and 4 males with estimated ages ranging from 5 to 10 years old; P7 (705,08 m2) with 7 pigtailed macaques, consisting of 4 females and 3 males with estimated ages ranging from 3 to 8 years old; P8 (340,04 m2) with 5 stump-tailed macaques of which 3 females and 2 males, with estimated ages ranging s from 10 months to 17 years old; P9 (233,03m2) with 5 stump-tailed macaques, consisting of which 3 females and 2 males with estimated ages ranging from 5 to 8 years old; P10 (51,72 m2) with 2 Assamese, 3 long-tailed and 2 pig-tailed macaques [7 in total], comprising 3 females and 5 males with estimated ages ranging from 2 to 12 years old; BP1 (50-100m2) with 3 pig-tailed macaques of which 1 female and two males with estimated ages ranging from 7 to 10 years old; and BP3 (50-100 m2) with 1 pig-tailed and 3 Assamese macaques [4 in total], consisting of 1 female and 3 males with estimated ages ranging from 10 to 13 years old.” All this is very difficult to follow, I suggest making a table with species, with number of individuals detailed in columns sex and age and what groups/enclosures it was in, but as Table 1 in the manuscript, not as supplementary.\nin “Table 1”: peers means same species, or could be another one? Please clarify in each case\n“Three human raters were…” Human sounds strange here I would say caregiver or something like that\nResults\nFrom tables 3 to 14 I believe that the results can be shown in column graphs or cakes with the significance, but the detailed numbers from these tables should be presented as supplementary.\nFor the figures presented, please put what it means directly in the footer and do not redirect to Table 1.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12812",
"date": "29 Nov 2024",
"name": "Miquel Llorente",
"role": "Author Response",
"response": "Thank you for your positive feedback. We are pleased that you have recognised the significance and novelty of our work. As you highlight, our research scientifically confirms the difficulty of rehabilitating animals rescued from human care for release. We hope our findings will contribute to improving rescue and rehabilitation practices in the field. However, it seems to me that the manuscript would need some adjustments in the abstract so it is understood precisely how the work was carried out. On the results a strong reduction of the text and of the tables presented is needed, making them more understandable for any reader in the form of graphs or histograms. Abstract Add that 53 focal subjects were studied within the resident macaques at Lao Conservation Trust for Wildlife center (LCTW). LCTW, a former zoo converted into an animal rescue and rehabilitation centre. When you mention social exposure, say that you are referring to individuals of the same species (if that is the case). We included the suggestion and details in the abstract. “The lack of juvenile social contact predicts reduced social behaviours and an inclination towards social avoidance in adulthood. Macaques raised by humans tend to exhibit more abnormal behaviours in social contexts, compromising their welfare. Deprivation of social exposure in infancy negatively impacts psychological stimulation and overall welfare. The duration of time spent in illegal trade correlates with heightened anxiety levels. Personality traits such as ‘Calmness’ and ‘Unfriendliness’ are influenced by rearing conditions, with macaques deprived of social interaction during their early years showing higher levels of introversion. In conclusion, the absence of social exposure during early life and hand-rearing due to illegal trade significantly shape” All of this could be summarized in a paragraph that makes it clear that the more human contact and the less with their own kind, anxiety levels intensify, etc., as is very well written in the conclusions. Thank you for your valuable feedback. I have revised the abstract to incorporate your suggestion, summarising the findings in a final paragraph that highlights how increased human contact and reduced exposure to conspecifics correlate with intensified anxiety, abnormal social behaviours, and impacted personality traits. I believe this adjustment clarifies the main conclusions and enhances the overall coherence of the abstract Introduction adverse childhood experiences (ACE) early adverse rearing experiences (EARE), what is the difference between these? Thank you for your question. 'Adverse Childhood Experiences' (ACE) is a term primarily used in human-focused literature to describe traumatic or negative experiences during childhood. In contrast, 'Early Adverse Rearing Experiences' (EARE) is commonly used in animal research to refer to similar early-life adversities in non-human subjects, such as macaques. This distinction helps to contextualise findings within the appropriate body of literature for each field. socio-emotional and behavioural (SEB). please mention this without the acronyms Thank you for the observation. We have removed the acronym, and 'socio-emotional and behavioural' is now written in full throughout the text “and four secondary goals” wich ones? Thank you for your insightful comment. We have revised the objectives section to eliminate the specific mention of primary and secondary goals, presenting the research aims in a more integrated manner. I believe this change enhances the clarity and flow of the text. “deprivation of social interactions”, always clarify with individuals of the same species Thank you for your suggestion. We have revised the text to clarify that 'deprivation of social interactions' refers specifically to interactions with individuals of the same species. We implemented this change consistently throughout the manuscript. Methods “Focal animals were ranged in ages between 1 and 18 years old.” Add here what the ages of infant/adolescent and adult are in each of these species. “Focal animals were ranged in ages between 1 and 18 years old (mean age _ SD = 8 _ 5 years) and were distributed across eleven groups/enclosures(Suppl. Table 1 in the extended data): P1 (651,56 m2) with 7 stump-tailed macaques (Macaca arctoides), consisting of 3 females and 4 males, with estimated ages ranging from 8 to 21 years old; P2 (653,76m2) with 8 stump-tailed macaques,including 4 females and 4 males, ranging in age from 1 to 15 years old; P4 (949,77 m2) with 3 Rhesus (Macaca mulatta),1 Assamese (Macaca assamensis) and 11 Northern pig-tailed macaques (Macaca leonina) [15 in total], of which7 females and 8 males with estimated ages ranging from 1 to 11 years old; P5 (1236,63 m2) with 8 Rhesus, 9 Assamese,1 pig-tailed and 1 long-tailed macaque (Macaca fascicularis) [19 in total], of which 9 females and 10 males withestimated ages ranging from 11 months to 11 years old; P6 (874,49 m2) with 3 Rhesus and 5 Assamese macaques [8 intotal], comprising 4 females and 4 males with estimated ages ranging from 5 to 10 years old; P7 (705,08 m2) with 7 pigtailed macaques, consisting of 4 females and 3 males with estimated ages ranging from 3 to 8 years old; P8 (340,04 m2) with 5 stump-tailed macaques of which 3 females and 2 males, with estimated ages ranging s from 10 months to 17 years old; P9 (233,03m2) with 5 stump-tailed macaques, consisting of which 3 females and 2 males with estimated ages ranging from 5 to 8 years old; P10 (51,72 m2) with 2 Assamese, 3 long-tailed and 2 pig-tailed macaques [7 in total], comprising 3 females and 5 males with estimated ages ranging from 2 to 12 years old; BP1 (50-100m2) with 3 pig-tailed macaques of which 1 female and two males with estimated ages ranging from 7 to 10 years old; and BP3 (50-100 m2) with 1 pig-tailed and 3 Assamese macaques [4 in total], consisting of 1 female and 3 males with estimated ages ranging from 10 to 13 years old.” All this is very difficult to follow, I suggest making a table with species, with number of individuals detailed in columns sex and age and what groups/enclosures it was in, but as Table 1 in the manuscript, not as supplementary. In response to your suggestion, I have created a table that clearly presents the details of the focal animals, including species, group/enclosure, number of individuals, sex distribution, and age range. This table will be included as Table 1 in the manuscript for clarity and ease of reference. Thank you for your helpful feedback! in “Table 1”: peers means same species, or could be another one? Please clarify in each case Yes, it means same species. We replace “peers” by “conspecifics” in the table. “Three human raters were…” Human sounds strange here I would say caregiver or something like that Thank you for the suggestion. We have removed \"human\" and kept \"three raters\" only, as these raters can be either veterinarians or researchers. Results From tables 3 to 14 I believe that the results can be shown in column graphs or cakes with the significance, but the detailed numbers from these tables should be presented as supplementary. We move tables 3 to 14 to supplementary materials as suggested by the reviewer, now renamed as tables 12 to 24."
}
]
},
{
"id": "294421",
"date": "26 Aug 2024",
"name": "Lief Erikson Gamalo",
"expertise": [
"Reviewer Expertise Wildlife and conservation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper provides a valuable contribution to the field and advances our understanding on impacts of trades on macaques' socio-emotional and behavioral skills. The research uses thorough methodology and analysis. Given its potential impacts to the field of conservation and animal welfare, this important piece of work is recommended to be indexed.\n\nHere are my comments and suggestions; 1. Authors should add authority in the first mention for each scientific names. 2. Page 3: \"...marmosets, Rhesus and long-tailed macaques...\" should be \"...marmosets, Rhesus, and long-tailed macaques\" 3. Page 4: \"LCTW, a former zoo converted into an animal rescue and rehabilitation centre.\" should be \"LCTW is a former zoo that has been converted into an animal rescue and rehabilitation centre.\" 4. Page 5: \"We thus focused on the study of 53 focal subjects within a broader sample of 88 macaques. Focal animals were ranged in ages between 1 and 18 years old.......ranging from 10 to 13 years old \". This paragraph is a little bit confusing. Maybe the authors can find a better way of presenting this? 5. Page 9: \"The SRS [short version] scale comprise....\". Delete \"[short version]\" 6. Pages 10-16: Starting with the subheading social responsiveness in Result section. To me, this portion distracted the main focus of the paper. Thus, I would suggest to make a separate section about the statistical process and results of the reliability of the questionnaire labeling it as questionnaire reliability or related terms. Make it concise. 7. Figures 1-12: I recommend that the authors should place the meaning of those codes in the figure description, instead of referring the readers to table 1.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12813",
"date": "29 Nov 2024",
"name": "Miquel Llorente",
"role": "Author Response",
"response": "This paper provides a valuable contribution to the field and advances our understanding on impacts of trades on macaques' socio-emotional and behavioral skills. The research uses thorough methodology and analysis. Given its potential impacts to the field of conservation and animal welfare, this important piece of work is recommended to be indexed. Response: Thank you very much for your kind and encouraging feedback. We are delighted to hear that you find the study valuable and recognise its contribution to the fields of conservation and animal welfare. Here are my comments and suggestions; 1. Authors should add authority in the first mention for each scientific names. Response: Thank you very much for your thoughtful suggestion regarding the inclusion of the authority for each scientific name. We appreciate your attention to detail. However, we have chosen not to include these, as it is uncommon in primatology literature to do so. We hope this approach aligns with standard practice and maintains clarity for our readers 2. Page 3: \"...marmosets, Rhesus and long-tailed macaques...\" should be \"...marmosets, Rhesus, and long-tailed macaques\" Response: Thank you, we included it. 3. Page 4: \"LCTW, a former zoo converted into an animal rescue and rehabilitation centre.\" should be \"LCTW is a former zoo that has been converted into an animal rescue and rehabilitation centre.\" Response: We modified the sentence as: “LCTW is a former zoo that has been transformed into an animal rescue and rehabilitation centre, currently housing over one hundred individuals from various macaque species, which were victims of poaching”. 4. Page 5: \"We thus focused on the study of 53 focal subjects within a broader sample of 88 macaques. Focal animals were ranged in ages between 1 and 18 years old.......ranging from 10 to 13 years old \". This paragraph is a little bit confusing. Maybe the authors can find a better way of presenting this? Response: We modified as: “In this study we investigated 53 focal subjects selected from a larger sample of 88 macaques. These focal animals, aged between 1 and 18 years old (mean age ± SD = 8 ± 5 years), were distributed across eleven groups/enclosures (Suppl. Table 1 in the extended data for biographic information).” 5. Page 9: \"The SRS [short version] scale comprise....\". Delete \"[short version]\" Response: Thank you for your observation. If possible, we would prefer to maintain '[short version]' to clearly differentiate it from the long version of the SRS, as this distinction is relevant for our methodology. 6. Pages 10-16: Starting with the subheading social responsiveness in Result section. To me, this portion distracted the main focus of the paper. Thus, I would suggest to make a separate section about the statistical process and results of the reliability of the questionnaire labeling it as questionnaire reliability or related terms. Make it concise. Response: Thank you for your valuable suggestion. We understand your concern regarding the potential distraction from the main focus of the paper. However, we prefer to maintain these sections and explanations, as we consider them necessary for understanding the subsequent statistical processes. To simplify the main text, we have moved a significant portion of the ICC tables, factor analysis, and item scores to the supplementary materials section 7. Figures 1-12: I recommend that the authors should place the meaning of those codes in the figure description, instead of referring the readers to table 1. Response: Thank you for your suggestion. While we understand your point, we prefer not to make this change as the meaning of each code may be quite lengthy and would not fit within the design of the figures. To maintain consistency throughout the manuscript, we have opted to continue using the codes in all figures and refer readers to Table 1 for their full explanation. Additionally, the other three reviewers have expressed no concerns about this design choice"
}
]
},
{
"id": "313260",
"date": "29 Aug 2024",
"name": "Augusto Vitale",
"expertise": [
"Reviewer Expertise ethology",
"ethics of research",
"animal experimentation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a very interesting and important piece of work. I am not in the field of conservation, but it looks like many of the conclusions would be simply common sense. However, often, science simply demonstrates the obvious with the support of scientific data.\nThe authors have achieved exaclty that: supporting important and \"common sense\" conclusions\" with an impressive quantity of results obtained adopting a strictly scientific methodology.\nAs I said, I am not in the field of conservation, but I suppose this article will become an important point of reference for the professionals involved in this specific field of primatology.\nI have a concern about the paper, and some stylistic suggestions.\nMy concern is that the first part of the Introduction must be significantly shortened. It gives the impression that the paper is about the welfare of monkeys in the lab, which is not at all. It is also confusing: it reads both like a report on how lab research has demonstrated the importance of the early -life trauma in the future development of adult behaviour, as well as a generalised and vague accusation of mis-treatment of primates used in lab reserarch. To a not specialised reader not familiar with primate lab research, gives the imression that primates in labs are inevitably subject to abuse and trauma. This is an unfair generalisation. Critical cases do exist, but the science of welfare of primates housed in research labs has made significant progress which cannot be simply dismissed. I strongly advice the authors to significantly cut the first part of the Introduction, and re-focus it.\nBeyond that, probably I would suggest to semplify the tables and present the numbers of the statistics in a supplementary part. Furthermore, do not refer to Table 1 for explanations that can be directly inserted in the text.\nI congratulate with the authors for this impressive and important research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12814",
"date": "29 Nov 2024",
"name": "Miquel Llorente",
"role": "Author Response",
"response": "This is a very interesting and important piece of work. I am not in the field of conservation, but it looks like many of the conclusions would be simply common sense. However, often, science simply demonstrates the obvious with the support of scientific data. The authors have achieved exactly that: supporting important and \"common sense\" conclusions\" with an impressive quantity of results obtained adopting a strictly scientific methodology. Response: Thank you very much for your kind words and for your thoughtful comments. We appreciate your perspective on the conclusions, and we fully agree that many of them may seem like common sense. However, we believe that common sense alone does not allow for the level of precision and detail required to fully understand the impact of such practices on animal welfare and the socio-emotional development of individuals. Through the scientific approach we adopted, we have been able to quantify and rigorously assess these effects, providing data that would otherwise be difficult to obtain or appreciate. For that, we suppose this article will become an important point of reference for the professionals involved in welfare and conservation of primates. I have a concern about the paper, and some stylistic suggestions. My concern is that the first part of the Introduction must be significantly shortened. It gives the impression that the paper is about the welfare of monkeys in the lab, which is not at all. It is also confusing: it reads both like a report on how lab research has demonstrated the importance of the early -life trauma in the future development of adult behaviour, as well as a generalised and vague accusation of mis-treatment of primates used in lab reserarch. To a not specialised reader not familiar with primate lab research, gives the imression that primates in labs are inevitably subject to abuse and trauma. This is an unfair generalisation. Critical cases do exist, but the science of welfare of primates housed in research labs has made significant progress which cannot be simply dismissed. I strongly advice the authors to significantly cut the first part of the Introduction, and re-focus it. Response: Thank you for your thoughtful feedback. We fully understand your concern about the first part of the introduction potentially being misinterpreted as focusing primarily on the welfare of macaques in lab settings, and we appreciate the suggestion to shorten it. Our intention was to provide context for the broader issue of early-life trauma in macaques, particularly in relation to the detrimental impacts of illegal trade and poaching, which are less well understood. The references to early adverse rearing experiences were meant to illustrate the continuum of trauma, which is central to our study, but we recognize that some readers may perceive this as too generalized. We will revise the introduction to make it more concise and focused, ensuring that the primary aim of our study is clearer from the outset, while retaining the necessary background to contextualize the research. We aim to strike a balance between presenting the wider issue and focusing on the specific research we report in this paper. We appreciate your constructive feedback, which will help us improve the clarity of the introduction. Finally, we also include this sentence to clarify to the readers: Nevertheless, it is important to note, that while early-life adversity can have significant long-term effects on the welfare of macaques, it would be inappropriate to generalise these findings to all laboratory settings. In recent years, there has been increasing recognition of the need for improved welfare standards for primates in research, with more stringent regulations and ethical guidelines now in place to ensure better living conditions and care. These advances in animal welfare practices aim to mitigate the negative impacts of early experiences, making it essential to avoid an overly broad characterisation of all laboratory environments as inherently detrimental. Beyond that, probably I would suggest to simplify the tables and present the numbers of the statistics in a supplementary part. Furthermore, do not refer to Table 1 for explanations that can be directly inserted in the text. Response: Thank you for your suggestion. We have already moved a significant portion of the tables, including statistical details, to the supplementary materials section to streamline the main text. Regarding the explanations, we prefer to refer to Table 1 for consistency and clarity, as it allows us to maintain a concise narrative in the main text while still providing detailed information in an accessible format for readers. I congratulate with the authors for this impressive and important research. Response: Thank you very much for your kind words and congratulations. We truly appreciate your positive feedback, and we are glad that you found the research valuable and impactful."
}
]
},
{
"id": "267641",
"date": "09 Sep 2024",
"name": "Lauren M. Robinson",
"expertise": [
"Reviewer Expertise Animal welfare",
"cognition",
"personality"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract: Clear and very easy to follow Introduction Overall, I find this to be well written with lots of great citations. My specific comments are as follows - These paragraphs are way too long, they need to be broken up for readability. - “In humans…” is a good place to break it up. - “In line with this…” is another good place. This paragraph can easily be broken into three. - “ multitude of factors, that include” delete comma - Delete “On top of that” as opening of next paragraph - ”being a victim of the trade along lifespan”, I don’t understand what this means. Across lifespan perhaps? - ”The use of wildlife”, paragraph break here - ”For all of that”, this is somehow too informal and confusing. All of what? What you just reviewed? I’d pick a new start to this paragraph. - ”Currently, LCTW houses more than one hundred individuals from various species of macaques, which were victims of poaching.” Is every animal there the victim of poaching? This sentence is confusing. - ” Furthermore, we considered”, delete furthermore - ”traumatic experiences including mother separation” comma between experiences and including - I like the predictions, they make sense. Though, development of these traits, doesn’t everyone have some sort of development? Would you be predicting an increased development or the like? It’s fine but a better wording wouldn’t hurt. Methods - Lots of great details here, very clear methods - I couldn’t find the supplementary table but I’m glad you have it as the writing is clear but it’s a huge chunk of text to take in. If there’s a cleaner way to do it with the table included, I’d recommend considering it. - ”three of them not being” instead of current word order Results - Very clear tables, easy to understand - I think the explained variance could probably go in supplementary as saying what was the highest is enough and this could save some space on a long paper - If I’m understanding correctly, you’re using 5 species in all of your structural work. How do you factor that in given the differences between macaque species? I see you accounted for it in the later analysis but it still could influence structure and thus scores before you get that far. I understand why you did it with that sample size but just want to understand how you considered its potential impact on your structures. - Very thorough statistics work - Boxplots are nice - Very interesting results Discussion - I like the discussion. It doesn’t go beyond the data but the work adds nicely to the existing research - I’d break up the personality paragraph, it’s quite long -”We suggest conducting additional research to thoroughly investigate macaque personality at the species-level”, yes this makes good sense - I like the suggestions for the future, very sensible\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12815",
"date": "29 Nov 2024",
"name": "Miquel Llorente",
"role": "Author Response",
"response": "Abstract: Clear and very easy to follow Thank you for your feedback. Introduction Overall, I find this to be well written with lots of great citations. My specific comments are as follows - These paragraphs are way too long, they need to be broken up for readability. - “In humans…” is a good place to break it up. - “In line with this…” is another good place. This paragraph can easily be broken into three. Thank you for your valuable feedback. We have reviewed the introduction and made adjustments to improve its readability. Specifically, we have shortened and broken up some of the longer paragraphs to enhance the flow and clarity of the text. We believe these changes will make the section more accessible for readers. - “ multitude of factors, that include” delete comma The deleted the comma. - Delete “On top of that” as opening of next paragraph We deleted it. - ”being a victim of the trade along lifespan”, I don’t understand what this means. Across lifespan perhaps? Thank you for pointing that out. We have revised the phrase \"across the lifespan\" to \"throughout the life course\" to provide clearer meaning and better align with the context. We hope this addresses your concern. - ”The use of wildlife”, paragraph break here Thank you, we broke the paragraph here. - ”For all of that”, this is somehow too informal and confusing. All of what? What you just reviewed? I’d pick a new start to this paragraph. We deleted this. - ”Currently, LCTW houses more than one hundred individuals from various species of macaques, which were victims of poaching.” Is every animal there the victim of poaching? This sentence is confusing. Thank you for your comment. We have revised the sentence to clarify that while most of the macaques at LCTW are victims of poaching, some were rescued from other forms of exploitation, and in some cases, the details of their past are not known. We hope this revision helps to address the confusion. - ” Furthermore, we considered”, delete furthermore We deleted “Furthermore”. - ”traumatic experiences including mother separation” comma between experiences and including We included the comma. - I like the predictions, they make sense. Though, development of these traits, doesn’t everyone have some sort of development? Would you be predicting an increased development or the like? It’s fine but a better wording wouldn’t hurt. Thank you for your insightful comment. We have revised the wording to clarify that we are predicting an increased development of certain traits, such as heightened neophobia, dominance, or neuroticism, as a result of adverse experiences. We hope this revised phrasing better conveys the intended meaning. Methods - Lots of great details here, very clear methods Thanks for your comment. - I couldn’t find the supplementary table but I’m glad you have it as the writing is clear but it’s a huge chunk of text to take in. If there’s a cleaner way to do it with the table included, I’d recommend considering it. Thank you for your feedback. The supplementary table is indeed included, and you can find the link to access all materials at the end of the article. We hope this will provide a clearer and more accessible way to review the information. - ”three of them not being” instead of current word order Thank you, we replaced it. Results - Very clear tables, easy to understand Thank you for your feedback. - I think the explained variance could probably go in supplementary as saying what was the highest is enough and this could save some space on a long paper Thank you for your suggestion. We have moved all the tables containing the details of the ICC values and the factor analyses to the supplementary materials, which should help save space in the main paper while still providing all the necessary information. - If I’m understanding correctly, you’re using 5 species in all of your structural work. How do you factor that in given the differences between macaque species? I see you accounted for it in the later analysis but it still could influence structure and thus scores before you get that far. I understand why you did it with that sample size but just want to understand how you considered its potential impact on your structures. Thank you for your insightful comment. We did not divide the factor analysis by species due to the sample size. We anticipated that there would not be significant differences across species, especially since many of the species were housed in the same facility. However, we acknowledge the potential impact of species differences on the structural findings. This is a valuable point, and we will include it in the discussion section as a consideration for future research: “On one hand, we expected to find similar personality traits to those in the reference study, due to the similarity of the backgrounds, despite the macaques being different species. It is important to note that although we did not divide the factor analysis by species due to sample size constraints, species differences could potentially influence the structural outcomes. Given that many of the macaque species in this study were housed in the same facility, we did not expect significant variation. However, future studies with larger sample sizes and separate analyses for each species would be beneficial in exploring these potential effects more thoroughly.“ - Very thorough statistics work Thank you for the feedback. - Boxplots are nice Thank you for the feedback. - Very interesting results Thank you for the feedback. Discussion - I like the discussion. It doesn’t go beyond the data but the work adds nicely to the existing research Thank you for the feedback. - I’d break up the personality paragraph, it’s quite long Thank you for the suggestion. We broke it. -”We suggest conducting additional research to thoroughly investigate macaque personality at the species-level”, yes this makes good sense Thank you for the feedback. - I like the suggestions for the future, very sensible. Thank you for the feedback."
}
]
}
] | 1
|
https://f1000research.com/articles/13-188
|
https://f1000research.com/articles/13-1006/v1
|
04 Sep 24
|
{
"type": "Research Article",
"title": "Posterior palatal seal recording: fact and reasons among Iraqi dentists",
"authors": [
"Shorouq M. Abass",
"Bayan S. Khalaf",
"Tameem K. Jassim",
"Aseel M. Al-Khafaji",
"Bayan S. Khalaf",
"Tameem K. Jassim",
"Aseel M. Al-Khafaji"
],
"abstract": "Abstract*\nBackgrounds The retention of the maxillary complete denture may be influenced by adequate recording in the patient’s mouth, marking, and carving of the post-dam on the maxillary cast. Failure to do so may lead to loss of retention. Successful denture construction with patient’s comfort could be achieved by effective methods of recording, marking, and carving of the post-dam. The aim of the study was to assess Iraqi dentists in their knowledge and application of the post-dam in maxillary complete dentures.\n\nMethods Questionnaires were distributed randomly through online Google Forms and 118 Iraqi dentists with different academic degree participated in the study. A multinomial logistic regression model was also used to assess the nominal outcome variables.\n\nResults A High percentage of 90.7% of Iraqi dentists with different academic degree stated that they had the knowledge about the vibrating lines and their location and 84.7% stated that they mark the post-dam on the master cast, while 15.3% stated that the dental technician marks it. More the half (52.5%) of the participants carved the post-dam, while 47.5% of the participants stated that the dental technician did it. For participants not marking the post-dam, 30.5% of the participants stated they depend on the dental technician in marking and/or carve the post-dam, while the fear of denture failure and loss of retention was observed in 25.4% of the participants, followed by 24.6% of participants forgetting to carve, 10.2% of participants had no information about carving, and 9.3% participants found it was difficult to carve.\n\nConclusions Within the limitations of the study, most Iraqi dentists with different academic degree stated that they had the knowledge on the location of vibrating lines. However, recording and carving the post-dam was influenced by the dentist’s personal preference and their dependency on the dental technician.",
"keywords": [
"Maxillary",
"complete denture",
"post-dam."
],
"content": "Introduction\n\nA successful prosthesis, accepted by a patient, is that prosthesis that functions effectively during mastication and speech and is adequately retained on the edentulous arches. Precise recording, marking, and carving of the posterior palatal seal (PPS) is an important step for the retention of the maxillary denture and overall treatment of the edentulous patient. Thus, the significance of the distal extent of the upper complete denture needs to be adequately performed.1,2\n\nMany researches were aimed to enhance the retention of the maxillary denture by enhancing the denture base adaptation to the supporting structures.3,4 Even the disinfection of dentures may have an influence on the dimensional stability and overall retention of the complete dentures or the damaging effects on denture base material itself.5,6 Such attempts enhanced the adaptation but did not eliminate the need for a PPS. The purpose of the PPS is to offer retention for a well-adapted upper denture and this is provided by an appropriate seal to reduce the effect of shrinkage from polymerization setting of the denture base material. In addition, the presence of the PPS prevents food accumulation between the posterior border of the denture and the soft palate, reduces gag reflex, and renders the extension of the posterior border of the denture more comfortable to the touch of the tongue.7 Adding additives to the denture base may enhance the strength of the denture base but the presence of the PPS itself can add extra strength for the posterior part of the upper complete denture.7,8\n\nThe preparation of the PPS should be performed with adequate understanding of palatal anatomy and the displaceability of the mucosa.9 The dentist should be responsible for recording, marking, and carving of the PPS and this responsibility and the completion of this step should not be shifted to the dental technician.1,2,9\n\nSkinner10 stated that “The most effective addition to increase retention is the post dam”. In spite of the recommendations through previous researches concerning the importance of the PPS during denture manufacturing, the preparation and position was often ignored by dentists and dental students.11 Thus, a significant number of dentures were unsuccessful due to inadequate carrying out of the PPS.12\n\nAdams13 investigated the methods for the PPS employed by clinicians and dental students during construction of complete dentures and determined how many carryout this step by themselves. He revealed that the location and measurements of the post-dam were overlooked or forgotten by the practitioners and dental students and placed in the hands of technicians. This showed the deficiency in attention given to the significance of the post-dam by the practitioners and dental students. There was a need for research directed to analyzing the reason for the decline in interest by students and experience dental clinicians for this step.\n\nA survey was prepared by Sunil and Jain12 to investigate registering the PPS among dentists and dental students. The survey showed that they had satisfactory knowledge of the anatomical landmarks associated with the PPS, but were poorly associated with the size, shape, location, and compressibility of the mucosa of the PPS. This reflected the need for highlighting the importance of the PPS and its role in complete denture retention and the satisfaction of the patient.\n\nTherefore, this study was aimed to evaluate the knowledge of Iraqi dentists with different academic degree for locating the vibrating lines, if Iraqi dentists mark and/or carve the post-dam, and what were the reasons for not recording the post-dam by the dentists themselves. The null and the alternative hypotheses for the study are shown with description in Table 1.\n\n\nMethods\n\nThis study was approved by the Committee for Ethics / College of Dentistry, University of Baghdad (project no. 357221, date: June 7, 2021) and was conducted from October 2022 to November 2022 in accordance with the Helsinki Declaration of Ethical Principles for Medical Research with Human Subjects. The consent form was distributed with the google form and gathered electronically. The consent form and the patient information sheet were written as recommended by the Committee for Ethics/College of Dentistry, University of Baghdad and the participants were aware of the aims of the research and the confidentiality of their personal information as they accepted to fill the google form questionnaire.\n\nThe questionnaire was shared as a google form online in different groups for Iraqi dentists with different academic degree on social media applications (WhatsApp and Telegram). The first part of the questionnaire consisted of the personal information for the participant including the age, sex, years of experience after graduation and academic degree; doctorate (Ph.D.), master's (M.Sc.), higher diploma (H.D.D.), and bachelor's (B.D.S). The second part consisted of four questions related to the study, as shown in Table 2. The data was analyzed by using IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp https://www.ibm.com/products/spss-statistics. for frequency distribution. In addition, a multinomial logistic regression analysis model was used to examine the association between the dentists' ability to detect the vibrating line, including age, years of experience after graduation, gender, and academic degree.\n\n\n\n• Yes.\n\n• No.\n\n\n\n• Dentist (You).\n\n• Dental technician.\n\n\n\n• Dentist (You).\n\n• Dental technician.\n\n\n\n• Fear from denture failure and loss of retention.\n\n• Have no information about carving.\n\n• Forget to carve before sending to dental laboratory.\n\n• Difficult to carve.\n\n• Depend on dental technician.\n\n\nResults\n\nThe Iraqi dentists with different academic degree who participated in the survey were 118 in number. Among the participants, 86 were female and 32 were male with an age range between 22 to 46 years.\n\nMost of the Iraqi dentists (90.7%) who participated in the survey stated that they know how to locate the vibrating lines, anterior and posterior, during maxillary removable denture construction and they answered by selecting “yes”, whereas 9.3% answered by selecting “No” (Table 3).\n\nMost of the participants (84.7%) answered that they “dentist” mark the post-dam on the master cast during maxillary removable denture construction while (15.3%) stated that the “dental technician” marks it (Table 4).\n\nMore than half of the participants surveyed (52.5%) reported that they “dentist” carved the post-dam on the master cast during maxillary removable denture construction (Table 5), while (47.5%) of the participates stated that the “dental technician” did it.\n\nThe percentage of participants who stated that they did not mark the post-dam on the master cast was 30.5% (Table 6) and depend on the dental technician. While, the fear from denture failure and loss of retention was 25.4%, followed by 24.6% forget to carve before sending to dental laboratory, 10.2% have no information about carving, and 9.3% difficult to carve.\n\nA multinomial logistic regression model was used to assess the understanding of Iraqi dentists' for locating the vibrating lines, whether they mark and/or carve the post-dam, and why the dentists did not record the post-dam themselves. However, only the academic degree showed a significant association. Age, experience after graduation, gender, and academic degree do not affect the participants' knowledge of locating the anterior and posterior vibrating lines during maxillary removable denture construction (Table 7).\n\na The reference category is Dental technician.\n\nb This parameter is set to zero because it is redundant.\n\nc † 0 = female; 1 = male, ‡ 0 = bachelor's (B.D.S); 1= higher diploma (H.D.D.); 2= master's (M.Sc.); 3= doctorate (Ph.D.)\n\nd * Indicates a significant difference between variables (P<0.05).\n\nBeing a B.D.S and a H.D.D dentist will reduce the chance of marking the post-dam on the master cast during maxillary removable denture construction by 18 and 19 units, respectively compared to dependence on the dental technician for this step (Table 7).\n\nBeing a B.D.S and a H.D.D dentist will increase the chance of carving the post-dam on the master cast during maxillary removable denture construction by 19 units compared to dependence on the dental technician for this step (Table 8).\n\na The reference category is Dental technician.\n\nb This parameter is set to zero because it is redundant.\n\nc † 0 = female; 1 = male, ‡ 0 = bachelor's (B.D.S); 1= higher diploma (H.D.D.); 2= master's (M.Sc.); 3= doctorate (Ph.D.)\n\nd * Indicates a significant difference between variables (P<0.05).\n\n\nDiscussion\n\nOne of the essential steps in treatment of edentulous patients is the construction of an appropriate denture with esthetically, functionally, and biologically acceptable features. The retention of the prosthesis is crucial to achieve these goals and the PPS plays a significant role in obtaining these features.2\n\nThe step for introducing the PPS in the prosthesis should be done by the dentist and should not be imposed on the dental technician.1,10\n\nThis study’s results revealed that Iraqi dentists stated that they had the knowledge for the location of the vibrating line and they marked it in the patient’s mouth. However, most of those who didn’t mark and/or carve the post-dam most likely depended on the dental technician and fear from denture failure and loss of retention.\n\nThe first alternative hypothesis was accepted for this study. Results showed that the highest percentage (90.7%) of the Iraqi dentists stated that they had the knowledge on the location of the vibrating lines. This may be related to the fact that the position of the vibrating lines had been taught in detail during the study in Iraqi Colleges of Dentistry. This result agreed with finding of Sunil and Jain12 who stated that the practitioners had an acceptable amount of knowledge. In their study they found that over half of the participants surveyed (57%) stated that they had knowledge on how to locate the vibrating lines, while 43% stated that they had no knowledge.\n\nThe second null hypothesis was rejected and the alternative hypothesis was accepted. Most of the participants (84.7%) stated that they mark the post-dam on the master cast during maxillary complete denture construction. This could be due to the confidence and adequate knowledge they have for this step. In addition, this step is essential to transfer the vibrating lines form the patients mouth to the maxillary cast and was a mandatory step that the students must do when constructing a complete denture during the college study in the Iraqi Colleges of Dentistry. Adams13 findings showed contradictory results in which most of dentists didn’t mark the post-dam on the maxillary cast. Also, our finding regarding the dentist carving the post-dam also disagreed with Adams13 since almost half of the participants (52.5%) reported that the “dentist” carves the post-dam during maxillary removable denture construction. Therefore, the third null hypothesis was rejected and alternative hypothesis was accepted. Krysinski and Prylinski14 suggested that the shape and depth of the PPS was influenced by the clinical experience and the ability to evaluate the mucosal compressibility in the post-dam area, as well as the practitioner’s hand-carving abilities. These findings were in accordance with this study, in which 25.4% of the participant didn’t mark the post-dam on the master cast, may be due to fear of denture failure and loss of retention, while 10.2% of the participants had no information and 9.3% considered carving as a difficult procedure. Therefore, the fourth alternative hypothesis was accepted.\n\nWithin the limitations of this study, most dentists with different academic degree stated they were familiar with the location of the vibrating lines, and they marked the post-dam. However, carving the post-dam was still a matter of subjective experience and they depending on dental technicians for this step. The marking of the post-dam may be related to several different reasons and the most common reason was that they depended on the dental technician in marking and/or carving the post-dam on the master cast followed by the fear from denture failure and loss of retention.\n\nThis study was approved by the Committee for Ethics / College of Dentistry, University of Baghdad (project no. 357221, date: June 7, 2021) The consent form was distributed with the google form and gathered electronically. The consent form and the patient information sheet were written as recommended by the Committee for Ethics/College of Dentistry, University of Baghdad and the participants were aware of the aims of the research and the confidentiality of their personal information as they accepted to fill the google form questionnaire.",
"appendix": "Data availability\n\nThe datasets generated by the survey study research during analysis the current study are available in the Zenodo repository. https://doi.org/10.5281/zenodo.13168769 16\n\nThis project contains following dataset:\n\n1. 2024-8-2 with safe harbor method.csv\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\n\n1. The datasets generated by the survey study research during analysis the current study are available in the Zenodo repository. https://doi.org/10.5281/zenodo.13299680 15\n\nThis project contains following dataset:\n\n2. Questionnaire of Iraqi Dentists.docx\n\nZenodo- Patient information sheet and Consent form. https://doi.org/10.5281/zenodo.13317785 17\n\nThis project contains following dataset:\n\n• Patient information sheet and Consent form\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nHardy IR, Kapur KK: Posterior border seal - its rationale and importance. J. Prosthet. Dent. 1958; 8(3): 386–397. Publisher Full Text\n\nParithimarkalaignan S: The post dam - A review. Indian J. Dent. 2014; 5: 71–76. Publisher Full Text\n\nKhalaf BS, Abass SM, Jassim TK: Dimensional stability of heat-activated acrylic resin at different time intervals by different flask cooling methods. Mustansiria Dent. J. 2008; 5(3): 274–280. Publisher Full Text\n\nFatihallah AA, Abdul-Razak RW, Ahmed AN: Teeth Displacement and Palatal Adaptation of autoclave Cured acrylic resin with Various Palates and Investments. J. Bagh. Coll. Dentistry. 2016; 28(1): 1–10. Publisher Full Text\n\nAbass SM, Ibrahem RA, Alkafaji AM: Effect of immersion in sodium chloride solution during microwave disinfection on dimensional stability, water sorption, and water solubility of denture base acrylic resin. J. Bagh. Coll. Dentistry. 2010; 22(3): 46–51.\n\nAbed AA, Al-Khafaji AM: Examining how PMMA and polyamide denture base materials' physical characteristics are affected by electrolyzed water used as a denture cleaner. Bionatura. 2023; volume 8(1): Article number 99. Publisher Full Text\n\nBindhoo YA, Thirumurthy VR, Jacob SJ, et al.: Posterior Palatal Seal: A Literature Review. International Journal of Prosthodontics and Restorative. Dentistry. July-September 2011; 1(2): 108–114. Publisher Full Text\n\nFatalla AA, Tukmachi MS, Jani GH: Assessment of some mechanical properties of PMMA/silica/zirconia nanocomposite as a denture base material. Conf. Ser.: Mater. Sci. Eng. 2020; 987(012031): 012031–012039. Publisher Full Text\n\nWinland RD, Young JM: Maxillary complete denture posterior palatal seal: variations in size, shape, and location. J. Prosthet. Dent. 1973 Mar; 29(3): 256–261. PubMed Abstract | Publisher Full Text\n\nSkinner EW, Campbell RL, Chung P: A clinical study of the forces required to dislodge maxillary denture bases of various designs. J. Am. Dent. Assoc. 1953; 47(6): 671–680. PubMed Abstract | Publisher Full Text\n\nGoyal S, Goyal MK, Balkrishanan D, et al.: The posterior palatal seal: Its rationale and importance: An overview. Eur. J. Prosthodont. 2014; 2(2): 41. Publisher Full Text\n\nSunil NSBA, Jain AR: Knowledge, Attitude and Perception of Methods and Materials Used for Recording Posterior Palatal Seal among Dental Practitioners and Dental Students. Biomed. Pharmacol. J. 2018; 11(1): 539–551. Publisher Full Text\n\nAdams M: A comparison of posterior palatal seal creation in complete dentures by students at the University of Pretoria and private practitioners 2015 MChD. School of Dentistry, University of Pretoria, South Africa.\n\nKrysinski ZJ, Prylinski M: Carving of a master cast to obtain a posterior palatal seal of a complete maxillary denture as performed by four prosthodontists: A pilot study. J. Oral Sci. 2007; 49(2): 129–132. PubMed Abstract | Publisher Full Text\n\nAbass SM, Khalaf BS, Jassim TK, et al.: Questionnaire of Iraqi Dentists. [Dataset]. August 12, 2024. Publisher Full Text\n\nAbass SM, Khalaf BS, Jassim TK: Assessment of Iraqi Dentists Knowledge of the Post-dam Recording [Dataset]. August 2, 2024. Publisher Full Text\n\nAbass S, Khalaf B, Tameem J, et al.: Patient information sheet and Consent form. [Dataset]. August 14, 2024. Publisher Full Text"
}
|
[
{
"id": "333845",
"date": "11 Nov 2024",
"name": "Khurshid Ahmed Mattoo",
"expertise": [
"Reviewer Expertise Prosthodontics that includes complete and partial removable prosthodontics",
"fixed partial prosthodontics including crown and bridge and implantology."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI have reviewed the paper thoroughly up to the methodology section. The methodology section is fundamentally inadequate, incorrect and completely unreliable. The authors have generated four different hypotheses at the beginning and to test that they have used one questionnaire which comprised just four questions. The authors have put their own questions in the measuring tool and have not found the reliability and validity of such questions. The introduction section is on average not related to the purpose of this study. The authors have failed to provide a context to their study in terms of what the posterior palatal seal area is, what it is comprised of and why its recording is relevant. There is no research related literature that has been referred by the authors. The referred literature is inappropriate and inadequate without reference to the concerned studies.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "333838",
"date": "11 Nov 2024",
"name": "Zena Wally",
"expertise": [
"Reviewer Expertise Biomaterials in Dentistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study assesses Iraqi dentists' understanding and use of post-dam in maxillary complete dentures. Although the research holds substantial merit, some concerns require further attention.\nProofreading: The entire manuscript would benefit from a thorough proofreading to correct grammatical errors and improve overall readability. Introduction: The introduction should include a review of existing research on the posterior palatal seal (PPS), emphasizing its significance and the commonly used methods for recording and carving the PPS. It should also address the challenges and variability in PPS recording and carving among practitioners, providing readers with a comprehensive and informed understanding of the topic. Discussion: The discussion section should critically evaluate the limitations of the study, which is an essential part of any research discussion. For example, the sample size and the reliance on self-reported data could be potential limitations, as dentists might overstate their knowledge or practices. Additionally, the generalizability of the findings to all Iraqi dentists or other regions should be addressed. The authors should clearly identify limitations that could affect the interpretation of the results. Rationale for the Study: The rationale for the study should justify why this research is important and its potential impact on the field of dentistry. It should explain the value of understanding the practices of Iraqi dentists and discuss how the findings could contribute to improving denture retention practices in Iraq and potentially in similar regions. Future Prospects: The authors should highlight the future potential for improving clinical education and patient outcomes, particularly through enhanced training in PPS techniques. References: Consider including more recent and relevant references published within the last 3-5 years to strengthen the manuscript and provide up-to-date insights.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12844",
"date": "23 Nov 2024",
"name": "Shorouq Abass",
"role": "Author Response",
"response": "Thank you for your insightful recommendations on our manuscript. Therefore, we will proceed to revise based on the details you have provided."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1006
|
https://f1000research.com/articles/13-1439/v1
|
27 Nov 24
|
{
"type": "Case Report",
"title": "Case Report: Case report: Macrophage activation syndrome due to multifocal tuberculosis in an immunocompromised patient",
"authors": [
"Salma Riahi",
"Sana Ammar",
"Houssem Hassen",
"Emna Souilem",
"Donia Mbarki",
"Yosra Dhaha",
"Mehdi Ksiaa",
"Amina Bouatay",
"Sana Ammar",
"Houssem Hassen",
"Emna Souilem",
"Donia Mbarki",
"Yosra Dhaha",
"Mehdi Ksiaa",
"Amina Bouatay"
],
"abstract": "Macrophage Activation Syndrome (MAS) is a serious and life-threatening complication defined by excessive immune activation. While it’s commonly associated with rheumatic diseases, infections can also trigger MAS, with tuberculosis being a rare but significant cause. This case report discusses a rare occurrence of Macrophage Activation Syndrome (MAS) caused by multifocal tuberculosis in an immunocompromised patient with Crohn’s disease receiving immunosuppressive treatment. The patient is a 26-year-old woman with Crohn’s disease who is being treated with azathioprine. She arrived at the hospital battling persistent abdominal pain, overwhelming fatigue, and fever. Upon examination, splenomegaly and ascites were noted. A chest X-ray revealed bilateral pleural effusion consistent with tuberculosis. A CT scan confirmed the presence of pleural, pericardial, and intraperitoneal fluid. Blood tests indicated pancytopenia, hyperferritinemia, and hypofibrinogenemia. The analysis of ascitic fluid suggested an exudate. The PCR test of the bone marrow aspirate was positive for tuberculosis without rifampicin resistance, and the smear showed hemophagocytosis images. The patient was diagnosed with Macrophage Activation Syndrome secondary to multifocal tuberculosis. This report delves into the complex relationship between MAS and tuberculosis, emphasizing the challenges in diagnosing MAS in such cases and the potential link to tuberculosis. The complex diagnostic landscape of multifocal tuberculosis, which can often mimic malignancies, underscores the importance of promptly detecting and starting anti-tuberculosis interventions for improved clinical outcomes and the prevention of associated complications.",
"keywords": [
"Macrophage activation syndrome",
"Multifocal tuberculosis",
"Immunosuppressive treatement."
],
"content": "Introduction\n\nMacrophage Activation Syndrome (MAS) is a rare but life-threatening disease characterised by excessive activation and proliferation of macrophages and T lymphocytes, leading to a cytokine storm and multi-organ dysfunction.1 While MAS is most commonly associated with rheumatic diseases, mainly systemic juvenile idiopathic arthritis and adult-onset Still’s disease, it can also be triggered by infections, malignancies, and certain medications.2 However, it is rarely reported as a complication of tuberculosis, especially in immunocompromised patients. The clinical presentation of MAS is generally brutal, associating persistent fever with bi or pancytopenia. The diagnosis of MAS can be challenging, as its clinical and laboratory features may overlap with those of the underlying disease or infection.3 We present a case of a 26-year-old woman treated with azathioprine for her Crohn’s disease complicated with multifocal tuberculosis and MAS.\n\n\nCase presentation\n\nA 26-year-old- woman was referred to our hospital with abdominal pain for five days, fatigue, and fever (39°C). Her medical history included Crohn’s disease in 2018 with inflammation located in the terminal ileum and was taking azathioprine. The patient declared no exposure history to active tuberculosis in the past. Her heart rate was 121 beats per minute, blood pressure 110/77 mmHg, respiratory rate 25 breaths per minute, and temperature 39 °C. The patient had splenomegaly without hepatomegaly or adenopathy. Shifting dullness and a positive fluid wave test were found. No other signs were reported on physical examination. A chest X-ray was performed, showing bilateral pleural effusion compatible with tuberculosis. An abdominal CT scan was conducted, revealing the presence of both pleural effusion and a significant volume of ascites. High axial sections through the thoracic base showed bilateral pleural and pericardial effusion ( Figure 1).\n\nAxial sections taken at portal time after injection of contrast agent showed abundant intra-peritoneal effusion ( Figure 2).\n\nA complete blood count showed normochromic normocytic anaemia, neutropenia, lymphopenia, and thrombocytopenia ( Table 1).\n\nThe patient had hyperferritinemia (1050 ng/mL), and the Fibrinogen level was at 1.5 g/l. Mild liver cholestasis was noticed (gamma-glutamyl transpeptidase (GGT) at 52 UI/L; alkaline phosphatase (ALP) at 184 UI/L). The triglyceride level was normal (0.8 mmol/L) and the electrolyte test showed hyponatremia (125 mmol/L). The low serum Ascites Albumin Gradient (SAAG) (<1.1g/dL) suggested that the ascitic fluid is an exudate. Fluid’s direct microscopic examination revealed no tuberculosis bacilli and the acid-fast stain was negative. No renal function abnormality was found. Viral serology HIV, HSV, HBV, HCV, EBV, and CMV were negative. The febrile cytopenia associated with the splenomegaly led to a bone marrow aspirate; an Xpert MTB/RIF PCR was performed and turned out positive. Rifampicin resistance was not detected. The bone marrow aspirate smear showed a reactional plasmocytosis and multiple hemophagocytosis images ( Figure 3).\n\nBone Marrow Biopsy was not performed. The patient was prescribed a daily oral therapy for tuberculosis, which included isoniazid, rifampicin, pyrazinamide, and ethambutol hydrochloride, and showed good progress. MAS was retained, due to clinical and biological criteria, and given the clinical course, we retained the diagnosis of multifocal tuberculosis complicated by MAS in an immunocompromised patient.\n\n\nDiscussion\n\nTuberculosis (TB) remains a significant cause of death globally. According to WHO, there were approximately 10.6 million new TB cases in 2021.4 TB is endemic in Tunisia, with an estimated incidence of 22.46/100,000 inhabitants in 2021.5\n\nIt is widely recognized that immunosuppressive therapy elevates the risk of tuberculosis, particularly in endemic regions like Tunisia.6 A study by Fortes et al. assessed 301 patients with inflammatory bowel disease (IBD) and found that azathioprine treatment increased the risk of developing active tuberculosis by 6.87 times compared to patients who were not receiving this medication.7 MAS is a serious medical condition that can be triggered by infectious agents, particularly certain viruses and mycobacteria. The majority of cases involving tuberculosis complicated by MAS occur in individuals who are immunocompromised.8 The disease presents significant challenges and is often associated with a poor prognosis. However, it is essential to approach this matter with a focus on early diagnosis and targeted treatment options, which can lead to improved outcomes and better management of the condition. In our case, MAS was due to multifocal tuberculosis, which involves multiple systems with associated symptoms, making the diagnosis challenging.\n\nMultifocal tuberculosis is characterised by large multifocal tuberculosis areas in the same or different adjacent or distant organs; in our case, the organs concerned were the lungs, the digestive system, and the hematopoietic organs.9 The prognosis is severe, with a mortality rate of 16 to 25%, depending on the author.10,11\n\nSporadic cases of multifocal tuberculosis have been reported; most of them presented with anaemia, leucopenia, and/or thrombocytopenia. In our case, the patient had pancytopenia.\n\nMAS is an acute, sometimes fatal complication of multifocal tuberculosis. The clinical presentation is usually non-specific and can be misleading. MAS is a condition associated with hemophagocytic lymphohistiocytosis (HLH), which is categorized into primary and secondary HLH. Primary HLH is a genetic disorder, while secondary HLH arises from other conditions, such as cancers, autoimmune disorders, and infections like tuberculosis, as seen in this instance. EBV is the most prevalent infectious cause, but MAS can also be related to various infections, including viral (HIV, CMV), bacterial (Salmonella typhi), and parasitic (Leishmania sp., Toxoplasma gondii) origins.12\n\nThere is a set of clinical and biological criteria to define a MAS, but according to the literature, some remain more important than others. The most used criteria were Hepatosplenomegaly, fever, cytopenia, hypofibrinogenemia, hyperferritinemia, hypertriglyceridemia, hemophagocytosis, and hepatopathy. Six out of all the criteria cited below ( Table 2) were found in our patient.13\n\n\n\n(1) Molecular diagnosis consistent with HLH\n\n(2) Diagnostic criteria for HLH fulfilled (5 out of the 8 criteria shown below)\n\n- Fever ≥38.5°C for ≥7 days\n\n- Splenomegaly ≥3 finger breadth below the left subcostal margin\n\n- Cytopenias affecting ≥2 of 3 lineages in peripheral blood\n\n• Hemoglobin <9 g/L\n\n• Platelets <100×109/L\n\n• Absolute neutrophil count <1.0×109/L\n\n- Hypertriglyceridemia and/or hypofibrinogenemia\n\nFasting triglycerides ≥265 mg/dL, Fibrinogen ≤1.5 g/L\n\n- Hemophagocytosis in the bone marrow or spleen or lymph node\n\n- Low or absent NK cell activity (according to the local laboratory reference)\n\n- Ferritin ≥500 μg/L\n\n- Soluble CD25 (sIL-2 receptor) ≥2,400 U/mL\n\nA study examined 37 documented instances of tuberculosis linked to MAS, revealing that half of the patients were immunocompromised (due to renal transplants, cancer, or HIV). The clinical symptoms remained consistent (such as fever and hepatosplenomegaly). In 80% of the cases, it was a disseminated tuberculosis.15\n\nIn most bone marrow aspirations, cellularity appears quite normal, and hemophagocytic histiocytes typically account for 2 to 75% of total nucleated cells. The mortality rate associated with MAS and tuberculosis reaches 50%, rising to 100% for those who do not receive any antituberculous treatment.16\n\n\nConclusion\n\nIn conclusion, we would like to present a rare case of MAS triggered by multifocal tuberculosis in a Crohn’s disease patient receiving immunosuppressive therapy. MAS is a severe complication that necessitates prompt diagnosis and management. Our case underscores the significance of considering atypical infectious symptoms in immunocompromised patients and promptly suspecting tuberculosis, particularly in patients exhibiting signs of MAS. Timely diagnosis and initiating antitubercular therapy are imperative for enhancing outcomes and averting complications.\n\n\nEthical consideration\n\nEthical approval was not required.\n\n\nConsent statement to Publish\n\nWritten informed consent was obtained from the patient upon admission, permitting the use of their de-identified data for research and publication purposes. All identifying information has been removed to ensure the patient’s confidentiality following ethical guidelines.",
"appendix": "Data availability statement\n\nNo data associated with this article.\n\n\nReferences\n\nRavelli A, et al.: Macrophage Activation Syndrome. Hematol. Oncol. Clin. North Am. 2015; 29(5): 927–941. Publisher Full Text\n\nCarter SJ, et al.: Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatology (Oxford). 2019; 58(1): 5–17. PubMed Abstract | Publisher Full Text\n\nMinoia F, et al.: Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J. Rheumatol. 2015; 42(6): 994–1001. PubMed Abstract | Publisher Full Text\n\nWHO: TB incidence, Global Tuberculosis Report 2022.Reference Source\n\nMansouri A, Bouguerra H, Belkahla M, et al.: Epidemiological Profile of Tuberculosis in Tunisia. Eur. J. Pub. Health. 1 oct 2023; 33(Supplement_2): ckad160.636. Publisher Full Text\n\nKedia S, Mouli VP, Kamat N, et al.: Risk of Tuberculosis in Patients With Inflammatory Bowel Disease on Infliximab or Adalimumab Is Dependent on the Local Disease Burden of Tuberculosis: A Systematic Review and Meta-Analysis. Am. J. Gastroenterol. March 2020; 115(3): 340–349. Publisher Full Text\n\nFortes FML, Rocha R, Santana GO: Thiopurines are an independent risk factor for active tuberculosis in inflammatory bowel disease patients. World J. Gastroenterol. 7 March 2023; 29(9): 1536–1538. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGartini S, Bougrini Y, Rhazari M, et al.: Macrophagic activation syndrome revealing disseminated multifocal tuberculosis: A case report of a rare clinical situation. Ann. Med. Surg. 1 April 2022; 76: 103487.\n\nWang C, Luan Y, Liu S, et al.: Multifocal tuberculosis simulating a cancer-a case report. BMC Infect. Dis. 10 July 2020; 20(1): 495. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDenis-Delpierre N, Merrien D, Billaud E, et al.: Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993. Pathol. Biol (Paris). June 1998; 46(6): 375–379. PubMed Abstract\n\nRezgui A, Fredj FB, Mzabi A, et al.: Tuberculose multifocale chez les immunocompétents. Pan Afr. Med. J. 4 May 2016; 24: 13.\n\nLe Hô H, Barbarot N, Desrues B: Pancytopenia in disseminated tuberculosis: Think of macrophage activation syndrome. Rev. Mal. Respir. March 2010; 27(3): 257–260. PubMed Abstract | Publisher Full Text\n\nBojan A, Parvu A, Zsoldos IA, et al.: Macrophage activation syndrome: A diagnostic challenge (Review). Exp. Ther. Med. August 2021; 22(2): 904. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim YR, Kim DY: Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults. Blood Res. 2021 Apr 30; 56(Suppl 1): S17–S25. Publisher Full Text\n\nBrastianos PK, Swanson JW, Torbenson M, et al.: Tuberculosis-associated haemophagocytic syndrome. Lancet Infect. Dis. July 2006; 6(7): 447–454. Publisher Full Text\n\nAzzeddine R, Elyassir F, Bourkadi JE: Multifocal tuberculosis complicated by a macrophage activation syndrome: about two cases. Pan Afr. Med. J. 2019; 32: 41."
}
|
[
{
"id": "347815",
"date": "30 Dec 2024",
"name": "W Winn Chatham",
"expertise": [
"Reviewer Expertise Systemic Lupus",
"Macrophage activation syndromes",
"Immunodeficiency associated autoimmunity"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a brief case report describing a patient diagnosed with disseminated tuberculosis who had features of associated macrophage activation syndrome, a previously recognized association.\nComments: As written, this report adds little if anything to existing knowledge. There are no apparent unique features of the case or relevant emphasized instructive teaching points.\n\nPerhaps discussions of the outcome of this case (no information was provided) would provide some instructive insights. What exactly is meant by \"MAS was retained\"? Did the MAS features abate with anti-tuberculous therapy and if so, what was the time frame?\nMissing relevant data: Were cultures or PCR studies performed and positive on the pleural and ascites fluids? As the fibrinogen was only borderline abnormal, were there other features of coagulopathy (elevated serum LDH, d-dimer, elevated PT/INR)? Was azathioprine toxicity considered or ruled out as a cause of the pancytopenia?\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? No",
"responses": []
},
{
"id": "357485",
"date": "03 Feb 2025",
"name": "Luisa Berenise Gámez-González",
"expertise": [
"Reviewer Expertise Clinical Immunology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt would be relevant to mention whether an immune workup was performed to rule out an underlying autoimmune or primary immunodeficiency condition, given the patient’s immunosuppressed state and the development of MAS.\nIt would be valuable to specify whether the patient required additional immuno-modulatory treatment (e.g., corticosteroids, ) beyond anti-tuberculosis therapy. Additionally, a more detailed description of the clinical course, including the time to improvement and resolution of MAS-related complications, would strengthen the discussion\nI suggest specifying the age at which Crohn’s disease was diagnosed instead of the year, as this provides clearer clinical context.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1439
|
https://f1000research.com/articles/13-1438/v1
|
27 Nov 24
|
{
"type": "Case Report",
"title": "Case Report: The tree that hides the forest, a case of renal ANCA vasculitis concurrent with Fabry nephropathy.",
"authors": [
"Rihem Dahmane",
"Awatef Azzabi",
"Yosra Zmantar",
"Nesrine THABET",
"Narjess Ben Aicha",
"Rahma Guesmi",
"Roua Farhat",
"Raja Boukadida",
"Amira Ben Afia",
"Nihed Abdessayed",
"Olfa Mahfoudh",
"Wissal Sahtout",
"Sanda Mrabet",
"Yosra Guedri",
"Dorsaf Zellama",
"Awatef Azzabi",
"Yosra Zmantar",
"Nesrine THABET",
"Narjess Ben Aicha",
"Rahma Guesmi",
"Roua Farhat",
"Raja Boukadida",
"Amira Ben Afia",
"Nihed Abdessayed",
"Olfa Mahfoudh",
"Wissal Sahtout",
"Sanda Mrabet",
"Yosra Guedri",
"Dorsaf Zellama"
],
"abstract": "This case report presents a complex case of a 65-year-old female with a history of hypertension and a family history of polycystic kidney disease and Fabry disease presented with acute pancreatitis and subsequent renal insufficiency. Despite initial corticosteroid therapy for immuno-allergic nephropathy, the patient’s condition deteriorated with the development of a skin rash, uremic syndrome, and neurological symptoms. A renal biopsy revealed cellular crescents and cytoplasmic vacuolization in podocytes and tubular cells. Genetic testing confirmed a GLA gene mutation, consistent with Fabry disease. While undergoing treatment with cyclophosphamide, the patient experienced severe allergic reactions, ultimately leading to acute respiratory distress syndrome and fatal outcome. Despite the Fabry disease variant being primarily associated with cardiac involvement, renal involvement was evident. This case highlights the rarity of this co-occurrence, the diagnostic challenges, the importance of genetic factors in autoimmune kidney diseases, and the impact of drug allergies on patient management.",
"keywords": [
"ANCA-associated vasculitis",
"Fabry disease",
"atopy",
"Fabry disease variant cardiac involvement"
],
"content": "Introduction\n\nFabry’s disease is a rare hereditary lysosomal storage disorder linked to the X chromosome, resulting from a deficiency of the enzyme α-galactosidase A.\n\nThis deficiency leads to the accumulation of the neutral glycosphingolipid globotriaosylceramide (GL-3) in various organs.1\n\nDiagnosis of Fabry disease (FD) is established through clinical evaluation, reduced activity of α-galactosidase A (GALA), and sequencing of cDNA or genomic DNA (gDNA). The c.644A > G mutation has predominantly been identified in patients with the cardiac variant of FD. This mutation was linked to renal involvement without cardiac symptoms in one case of homozygosity and in two other family members.2\n\nANCA-associated vasculitides (AAVs) are a type of inflammatory disease that affects small blood vessels throughout the body. People with AAVs have autoantibodies (abnormal proteins) that attack their own neutrophils, a type of white blood cell. This can lead to inflammation and damage in various organs, including the lungs and kidneys.3\n\nThis report describes an unusual case of Fabry’s disease (c.644A > G mutation) in conjunction with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) occurring in the context of atopy\n\n\nCase report\n\nA 65-year-old patient with a personal history of arterial hypertension and family history revealed that his mother, sister and brother were being followed for polycystic kidney disease, and his grandson was being followed for Autisme Spectrum Disorder secondary to Fabry disease as expressed on pedigree ( Figure 1).\n\nIn February 2024, the patient was admitted to the general surgery department for the management of acute pancreatitis, stage E of lithiasis origin. An allergy to ertapenem has been detected.\n\nDuring the hospitalization, renal insufficiency was discovered with a creatinine level of 150 micromol/l, for which she was referred to the nephrology consultation.\n\nThree months after the episode of acute pancreatitis, the patient developed a skin rash and uremic syndrome, with creatinine levels reaching 1000 micromol/l. A recent intake of allopurinol was noted.\n\nThe diagnosis of immuno-allergic nephropathy was made, and the patient was started on corticosteroid therapy at 0.5 mg/kg/day, leading to a return to baseline creatinine levels within one month. When renal function failed to improve, an immunological work-up revealed pANCA vasculitis, The patient was referred to us for a kidney biopsy. She was admitted to our nephrology department.\n\nThe clinical examination revealed a blood pressure of 160/100 mmHg with the presence of a skin rash without oedema of the lower limbs. The neurological examination was without anomalies. The diuresis was preserved.\n\nThe patient’s clinical progression included the development of headaches, photophobia, and gait disturbances, characterized by a cautious ataxic gait and a multidirectional positive Romberg sign. Brain MRI showed multiple FLAIR signal abnormalities in the superficial white matter, presenting as punctiform and nodular lesions, as well as confluent periventricular patches, consistent with vascular leukoencephalopathy classified as Fazekas 2 associated with diffuse pachymeningitis and an old ischemic lesion in the right cerebellum (Figures 1, 2, 3). These findings are all indicative of vasculitis.\n\nUrinalysis revealed hematuria and proteinuria (3.8 g/day).\n\nA renal biopsy was performed, and treatment with corticosteroid therapy (3 boluses of Solumedrol followed by oral prednisone at 1 mg/kg/day) and cyclophosphamide (600 mg/m2 on days 0, 15, and 30) was initiated.\n\nThe renal biopsy showed cellular crescents and cytoplasmic vacuolization in podocytes and tubular cells ( Figures 4, 5, 6, 7).\n\nImmunofluorescence revealed no IgG, IgA, IgM, C3, or C1q deposition.\n\nA bronchoscopy with bronchoalveolar lavage was performed, which ruled out alveolar hemorrhage.\n\nFabry disease was suspected due to the presence of anhidrosis, acroparesthesia. A genetic investigation was conducted, confirming the GLA gene mutation (heterozygous for the c.644A>G,p. Asn215Ser mutation). This mutation primarily leads to cardiac involvement.\n\nThe echocardiogram revealed hypertensive heart disease.\n\nThe patient underwent two courses of cyclophosphamide and during the second course, she developed symptoms of fever, chills, vomiting, and a generalized skin rash, which resolved after discontinuing the infusion, administering Unidex, and taking antihistamines.\n\nA pharmacovigilance investigation confirmed allergies to ertapenem, allopurinol, and cyclophosphamide.\n\nUnfortunately, before the Rituximab treatment could be initiated, the patient developed acute respiratory distress syndrome due to pneumonia, necessitating admission to the intensive care unit and mechanical ventilation. Sadly, the patient did not survive.\n\n\nDiscussion\n\nWe present a rare and intriguing case of the coexistence of Fabry’s disease (FD) and ANCA-associated vasculitis in the context of atopy. Fabry’s disease was suspected due to the patient’s history of anhidrosis, acroparesthesia, and hypoacusis, as well as the family history of Fabry’s disease in her grandson, who was diagnosed through genetic testing conducted as part of an autism evaluation and treated with enzyme replacement therapy. Histological examination of the renal involvement in our patient revealed in addition to the presence of cellular crescents associated with vasculitis, cytoplasmic vacuolization in podocytes and tubular cells. Immunofluorescence was negative.\n\nHowever, these findings cannot be attributed to Fabry’s disease, as the detected GLA gene variant (mutation c.644 A>G) is known to be pathogenic but primarily affects the heart, not explaining the renal involvement in our patient.\n\nIn the same context, Singh and Hanaoka reported 3 cases of patients with combined FD and pauci-immune necrotizing and crescentic glomerulonephritis but the pathogenic relationship between these two conditions is still unclear. Low peripheral leukocyte α-Gal-A activity was observed in all the cases.4,5\n\nPauci-immune glomerulonephritis was confirmed in the three cases. Notably, only the case of Hanaoka tested positive for PR3-ANCA and was definitively diagnosed with granulomatosis with polyangiitis (GPA).5\n\nAll the patients received high-dose prednisolone, with cyclophosphamide added. No deaths have been reported.\n\nThe possible explanation for the association between FD and ANCA-associated vasculitis could be linked to immune system dysregulation caused by lysosomal dysfunction, which may lead to abnormal immune responses. The accumulation of galactocerebroside in Fabry’s disease may be immunogenic, potentially triggering immune-mediated disease processes. This immune imbalance could potentially trigger the development of autoimmune conditions such as ANCA-associated vasculitis in patients with Fabry disease.6\n\nOn the other hand, an association between atopic conditions and ANCA-associated vasculitis has been reported in the literature.\n\nIndeed, neutrophils play a central role in the pathology of vasculitis. Proinflammatory cytokines can prime neutrophils, leading to the translocation of ANCA antigens from lysosomal compartments to the cell surface during the early stages of inflammation. When ANCA antigens on the cell surface engage with their antibodies and interact with Fc receptors, it activates the neutrophils.7\n\nGómez and al. reported the case of a patient followed since childhood for allergic reactions, including allergic eczema, who developed ANCA-associated vasculitis in adulthood. This case underlines the potential link between a background of atopy and the later development of ANCA vasculitis, highlighting the importance of close monitoring in such patients as they grow older.8\n\nIn our patient, a history of atopy preceded the onset of ANCA-associated vasculitis. Specifically, the patient had multiple allergic reactions to treatments such as ertapenem, allopurinol, and cyclophosphamide. However, the blood tests did not reveal any associated hyper-eosinophilia.\n\nA study on serum IgE and clinical symptomatology of atopy in patients with FD, a lysosomal storage disorder, explores how this condition impacts IgE levels and the manifestation of atopic symptoms. The research aims to understand the relationship between lysosomal dysfunction and the prevalence of atopic disorders, which may include conditions such as asthma, eczema, and allergic rhinitis.\n\nAmong patients (both male and female) with FD, whether receiving enzyme replacement therapy or not, clinical symptoms of atopic asthma, allergic rhinitis, and atopic eczema were observed. Some patients, including 2 out of 12 men and 6 out of 19 women, had total IgE concentrations exceeding 100 kU/L.9\n\nThe study concluded that patients with FD may exhibit an increased total serum IgE concentration and may present with symptoms of atopic disorders at rates similar to those observed internationally in individuals without FD.9\n\nAs for the association between Fabry disease and polycystic kidney disease, this case report describes a 60-year-old man with both Fabry disease and polycystic kidney disease, underscoring the significance of considering multiple kidney conditions in patient evaluation. Such comorbidity is particularly relevant in families with a history of either disease. To better understand the complex interplay between these conditions and the role of genetic factors, further research is imperative. This knowledge could have significant implications for patient diagnosis, management, and prognosis.10\n\n\nConclusion\n\nThe coexistence of Fabry’s disease with other renal diseases is rarely reported in the same patient.\n\nThis case demonstrates the simultaneous occurrence of Fabry’s disease and ANCA-associated vasculitis in a patient with an atopic predisposition.\n\nA causal relationship between the different pathologies can be explained by the pathophysiological and immunological mechanisms involved in these diseases.\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patient.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgments\n\nThe authors are sincerely grateful to the patient for giving the permission to share this informative report.\n\n\nReferences\n\nBrady RO, Gal AE, Bradley RM, et al.: Enzymatic defect in Fabry’s disease. Ceramidetrihexosidase deficiency. N. Engl. J. Med. 1967, May 25; 276(21): 1163–1167. Publisher Full Text Reference Source\n\nLin HH, Huang CW, Lin SH, et al.: Novel sequence variants of the α-galactosidase A gene in patients with Fabry disease. J. Mol. Neurosci. 2008; 36(3): 237–242. Reference Source\n\nHoffman GS, Kerr GS, Leavitt RY, et al.: Wegener granulomatosis: An analysis of 158 patients. Ann. Intern. Med. 1992, March 15; 116(6): 488–498. PubMed Abstract | Publisher Full Text\n\nSingh HK, Nickeleit V, Kriegsmann J, et al.: Coexistence of Fabry’s disease and necrotizing and crescentic glomerulonephritis. Clin. Nephrol. 2001, January; 55(1): 73–79. PubMed Abstract\n\nHanaoka H, Hashiguchi A, Konishi K, et al.: A rare association between Fabry’s disease and granulomatosis with polyangiitis: A potential pathogenic link. BMC Nephrol. 2014, October 1; 15(1): 157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHamers MJCN, Donker-Koopman WE, Coulon-Morelec MJ, et al.: Characterization of antibodies against ceramidetrihexoside and globoside. Immunochemistry. 1978, June 1; 15(6): 353–358. PubMed Abstract | Publisher Full Text\n\nNtatsidis G, Bajeena W, Jayne DRW: Pathogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies. Arthritis Res. Ther. 2006; 8(5): R130.\n\nGratacós Gómez AR, González Jimenez OM, Joyanes Romo JB, et al.: Eosinophilic Granulomatosis with Polyangiitis and Atopy: A Case Report. Exploratory Research and Hypothesis in Medicine. 2021, June 25; 6(2): 80–83.\n\nMöhrenschlager M, Ring J, Skovgaard E, et al.: A study on serum IgE and clinical symptomatology of atopy in patients suffering from the lysosomal storage disorder Fabry disease. J. Eur. Acad. Dermatol. Venereol. 2008; 22(11): 692–695. Publisher Full Text\n\nJohar L, Lee G, Martin-Rios A, et al.: Polycystic kidney disease complicates renal pathology in a family with Fabry disease. Mol. Genet. Metab. Rep. 2022 Nov 14; 33: 100934. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "344125",
"date": "10 Dec 2024",
"name": "Merve Emecen Sanli",
"expertise": [
"Reviewer Expertise I am an associate professor specializing in inherited metabolic diseases",
"with a research focus on lysosomal storage diseases",
"glycogen storage diseases",
"and gene therapies for rare disorders"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBackground of the Case: The background section is somewhat superficial and contains incorrect connections between the conditions. For instance, the claim of 'Autism Spectrum Disorder secondary to Fabry disease' is inaccurate, as there is no established direct link between Fabry disease and autism spectrum disorder. Genetic Mutation Discussion: The c.644A>G, p.Asn215Ser mutation is primarily associated with cardiac involvement in Fabry disease. However, it is important to note that many patients with this mutation present with renal involvement without accompanying cardiac symptoms (1). This distinction should be clarified. Immunological Work-Up: When renal function did not improve, an immunological work-up revealed pANCA vasculitis. This section should be expanded to include the specific laboratory results for clarity and accuracy. Brain MRI Findings: The brain MRI showed multiple FLAIR signal abnormalities in the superficial white matter, appearing as punctiform and nodular lesions, along with confluent periventricular patches. These findings could be associated with either Fabry disease or vasculitis, and the argument should be presented more cautiously to avoid confusion between the two possible causes. Renal Biopsy Findings: The renal biopsy revealed findings characteristic of both Fabry disease (cytoplasmic vacuolization in podocytes) and vasculitis (cellular crescents). However, in the case report section, these findings are attributed solely to vasculitis. This should be revised to reflect the dual pathology present in the biopsy. Systemic Dysfunction in pANCA Vasculitis: The patient's history should include a more detailed account of other systemic dysfunctions related to pANCA vasculitis. This information would provide a more comprehensive understanding of the patient's condition. Atopy and Allergic Reactions: In the discussion, the statement \"a history of atopy preceded the onset of ANCA-associated vasculitis\" is inaccurate. Specifically, the patient experienced multiple allergic reactions to treatments such as ertapenem, allopurinol, and cyclophosphamide, but blood tests did not indicate associated hyper-eosinophilia. Therefore, it is misleading to label the patient as having atopy based solely on these reactions. Discussion Section Final Paragraph: The final paragraph of the discussion is somewhat confusing and would benefit from restructuring. The ideas presented are unclear, and a more concise and logical flow would improve comprehension.\n\nIs the background of the case’s history and progression described in sufficient detail? No\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? No",
"responses": [
{
"c_id": "13065",
"date": "06 Jan 2025",
"name": "Rihem Dahmane",
"role": "Author Response",
"response": "We sincerely appreciate the reviewer’s insightful feedback, which has helped us identify key areas for improvement in the case report. Below, we address each point raised: 1. Background of the Case The discovery of Fabry disease occurred during the investigation of autism spectrum disorder (ASD) in the patient’s grandson, which prompted a broader genetic study. Each time, ASD was associated with Fabry disease. However, we acknowledge the lack of an established direct link between Fabry disease and ASD. This section will be revised to clarify the context and remove any misleading connections. 2. Genetic Mutation Discussion We have clearly specified that the c.644A>G, p.Asn215Ser mutation is primarily associated with cardiac involvement in Fabry disease. However, the renal involvement observed in our patient cannot be fully explained by this mutation and could potentially be secondary to hypertension. This distinction will be clarified in the revised manuscript. 3. Immunological Work-Up The immunological findings will be expanded to include detailed laboratory results, such as pANCA levels, inflammatory markers, and renal function tests, to enhance the clarity and accuracy of this section. 4. Renal Biopsy Findings The renal biopsy revealed findings characteristic of both Fabry disease (cytoplasmic vacuolization in podocytes) and vasculitis (cellular crescents). We will update the manuscript to reflect this dual pathology more accurately, ensuring that both conditions are appropriately acknowledged. 5. Systemic Dysfunction in pANCA Vasculitis The patient’s history will be expanded to include a more detailed account of systemic dysfunctions associated with pANCA vasculitis. In this case, the main manifestations were renal and neurological involvement, which will be emphasized to provide a clearer understanding of the patient’s condition. 6. Atopy and Allergic Reactions The patient was referred to a pharmacovigilance consultation, where a pharmacovigilance study confirmed allergic reactions to treatments such as ertapenem, allopurinol, and cyclophosphamide. We will revise the discussion to accurately describe these findings without attributing them to atopy, as there was no associated hyper-eosinophilia or other diagnostic evidence for atopy. 7. Discussion Section Final Paragraph The final paragraph of the discussion will be restructured to improve clarity and logical flow. We will ensure the key findings, their implications, and their relevance to understanding disease processes, diagnosis, and treatment are presented concisely and coherently. We are grateful for the reviewer’s constructive comments and will incorporate these changes to ensure the manuscript meets the required scientific standards."
}
]
},
{
"id": "357370",
"date": "24 Jan 2025",
"name": "Bernard Paelinck",
"expertise": [
"Reviewer Expertise Cardiology (cardiac imaging)"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors present a peculiar case of ANCA-associated vasculitis with renal insufficiency and Fabry disease.\nThere are several issues needing additional clarification:\n1. Case description:\nProvide (known) Fabry disease affected family members in the tree (Figure 1). Provide arrows/arrowheads to show lesions on Figures 2 - 7. Add legends for all Figures. Presence of anhidrosis, acroparestesia and acousis since when? In childhood (\"classical Fabry\") or later? The echocardiogram revealed \"hypertensive heart disease\": change in: \"left ventricular hypertrophy\". AGAL-dosage performed? Value?\n\n2. Discussion:\nWhy do the authors state that: \"However, these findings cannot be attributed to Fabry’s disease, as the detected GLA gene variant (mutation c.644 A>G) is known to be pathogenic but primarily affects the heart, not explaining the renal involvement in our patient\"? Please explain.\nAGAL-dosage associated with symptoms?\nWas treatment for Fabry initiated?\nDiscuss shortly the differences/clues in diagnosing Fabry disease in women (as opposed to men) (Arbelo, EHJ 2023) and how this could have been important in this case?\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1438
|
https://f1000research.com/articles/13-1233/v1
|
15 Oct 24
|
{
"type": "Case Report",
"title": "Case Report: Case report: Aslanger’s sign in electrocardiogram.",
"authors": [
"Haifa Bradai",
"Sondes Laajimi",
"Rabeb Mbarek",
"Nabil Chebbi",
"Dorra Loghmari",
"Mounir Naija",
"Naoufel Chebili",
"Haifa Bradai",
"Sondes Laajimi",
"Nabil Chebbi",
"Dorra Loghmari",
"Mounir Naija",
"Naoufel Chebili"
],
"abstract": "Electrocardiograms (ECGs) can be affected by various factors and technical problems. It is rare for an artefact to be the cause of ST-segment elevation, especially in asymptomatic patients. An important distinction between true ST segment elevation caused by myocardial infarction and an artefact is that the baseline elevation in an artefact may begin before or after the appearance of the QRS complex. When confronted with an abnormal ECG with suspicious waveform contours and possibly only one completely normal limb lead, the diagnosis of arterial pulse artefact should be considered. It is important to exclude subjective assessments unless they are clearly labelled as such. When encountering an abnormal ECG with suspicious waveform contours and possibly only one completely normal limb lead, the diagnosis of arterial pulse artefact should be considered.",
"keywords": [
"Arterial pulse–tapping artifact",
"electrocardiographic artifact",
"pseudo-myocardial infarction."
],
"content": "Introduction\n\nIt should be noted that artefacts on an electrocardiogram can result from a variety of causes, both internal and external. These include muscle tremors, the use of dry electrode gel and loose leads, and electromagnetic interference. These artifacts can sometimes mimic ECG abnormalities, which can cause problems for patient care.\n\nIn this report, we describe an unusual ECG artifact that caused large and bizarre T-waves on the ECG, The observed changes are aligned with those commonly associated with primary repolarisation changes characteristic of acute coronary syndrome. The artefact in question is caused by the overlapping of the artery pulse; this can be avoided by ensuring that the correct position is maintained. This is also known as the electromechanical association artefact.\n\n\nCase report\n\nA 68-year-old man with no medical history and no cardiovascular risk factors consulted the emergency department of a district hospital due to 48 hours of atypical and paroxysmal chest pain (tingling). His physical examination revealed no abnormalities, with SBP at 120 mmHg, DBP at 50 mmHg, HR at 99 bpm, RR at 20/min, Sat O2 at 96% on air, T° at 37°C, and finger blood sugar at 0.9 g/l.\n\nFigure 1 shows the patient’s first ECG.\n\nThe 12-lead ECG revealed a normal sinus rhythm with a heart rate of 80 beats per minute and normal axis. Abnormal T waves with bizarre morphology were observed in leads I, II, aVL, aVR, aVF, and from V1 to V6 in precordial leads. This abnormality was also observed in the 11-lead ECG, except for lead III, which was normal The emergency department physician’s interpretation of the T waves was that they were indicative of an ischaemic hyperacute condition. The patient was transferred to the emergency department (ED) at the university hospital due to suspected acute coronary syndrome. However, the ECG performed in the ED was completely normal (Figure 2), and the high-sensitivity cardiac troponin (hs-cTn) levels were twice negative. Therefore, the pre-hospital ECGs were recognized as artifacts, and the patient was discharged home.\n\n\nDiscussion\n\nIn this case, the electrocardiogram (ECG) showed anomalous T waves with unusual morphology in leads I, II, aVL, aVR, aVF, and V1 to V6. This distinct pattern was observed in the 11-lead ECG, with the exception of lead III. The presence of an arterial pulse-tapping artifact, also known as electromechanical association (EMA) or Aslanger’s sign, was indicated by the synchronous occurrence of this abnormality with the cardiac cycle. Aslanger initially described this phenomenon,1 which some authors refer to as Aslanger’s sign.2\n\nThe EMA artifact arises from the transmission of arterial pulsations, typically from the radial artery, onto the lead clips, generating aberrations in the ECG waveform. Contemporary electrocardiogram machines only record lead I and lead II, deriving the waveforms for other leads from these two. However, the majority of limb leads and augmented leads are susceptible to artifact. A consistent feature of EMA artifacts is the sparing of one lead, contingent on the limb generating the artifact. This serves as a crucial diagnostic clue, as outlined by Aslanger.3 In this case, lead III was unaffected as it represents an ECG recording between the left arm and left leg. Therefore, we concluded that the source of the artifact was the right arm. When the clip was placed proximally during a repeat ECG in the emergency department, the 12-lead ECG exhibited no artifacts.\n\nAslanger’s sign has been recently described and there are limited reported cases in the literature. It is important to emphasise the potential risks associated with this condition, as it can mimic symptoms of acute coronary syndrome. This can lead to unnecessary invasive investigations if not promptly recognised. The artifact, induced by the mechanical tapping of the pulse on the ECG electrode, is in synchrony with the cardiac cycle and can manifest as ST segment changes (elevation or depression) accompanied by peculiar T waves.4,5\n\n\nConclusion\n\nThis report presents a case of Aslanger sign, also known as arterial pulse-tapping ECG artifact. This anomaly presents as a primary repolarisation abnormality that is comparable to those observed in acute coronary syndrome.\n\nIt is important to be aware that an EMA artefact will almost always spare one of the limb leads, as this is a key factor in diagnosing it, which helps physicians avoid misinterpretation and unnecessary explorations.\n\n\nDeclarations\n\nInformed written consent for participation in the study was obtained.\n\nWritten informed consent for publication of his clinical details and/or clinical images was obtained from the patient.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nReferences\n\nAslanger E, Bjerregaard P: Mystery of “bizarre electrocardiogram” solved. J. Electrocardiol. 2011 Nov-Dec; 44(6): 810–811. PubMed Abstract | Publisher Full Text\n\nTakahashi K, Yamamura N, Yoshino M, et al.: Unfamiliar waveforms spanning from the ST to TP segments only observed in certain limb leads of the standard 12-lead electrocardiogram due to Aslanger’s sign. J. Geriatr. Cardiol. 2023; 20(9): 693–696. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAslanger E, Yalin K: Electromechanical association: a subtle electrocardiogram artifact. J. Electrocardiol. 2012; 45: 15–17. PubMed Abstract | Publisher Full Text\n\nSotananusak T, Meemook K: Asymptomatic ST-Segment–Elevation ECG in Patient with Kidney Failure. Circulation. 2018; 137: 402–404. PubMed Abstract | Publisher Full Text\n\nTakahashi K, Morioka H, Uemura S, et al.: Aslanger’s sign in 12-lead electrocardiogram. Oxf. Med. Case Rep. March 2023; 2023(3). PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "336521",
"date": "31 Oct 2024",
"name": "Nihal Sheriff",
"expertise": [
"Reviewer Expertise ECG"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors here have compiled a case report of an acute coronary syndrome mimic – “Aslanger sign” which has quite recently received attention in the field of cardiology. They have done a good job in summarising the necessary points regarding the same. That said, the following parts may need a bit explaining/ corrections for the report to be more informative to the audience.\nIn the abstract section, the sentence regarding suspicious waveform contours with one completely normal limb lead appears to be repeated. The fact to exclude subjective assessments can be better framed for easy understanding.\nThe introduction section seems to be crisply constructed. Just one suggestion here would be to reframe the sentence as \"the artefact can be avoided by moving the lead away from the pulsating artery\".\nIn the case report section, the history seems enough. However, the necessary investigations that need to be done in such a case seem to be lacking or have not been provided by the authors. Since the Aslanger sign is seen in hyperdynamic conditions, it would have been informative if the authors had disclosed the relevant blood investigations to rule out hyperthyroidism, cirrhosis or severe anemia (Takahashi K et al. 2023 [Ref - 1]) and also considering the fact that the patient had a pulse pressure of 70mmHg, it would have been prudent to rule out aortic regurgitation by echocardiography.\nA minor correction here would be “the abnormality was observed in all the leads except for lead III..” rather than \"11-lead ECG\"\n\nThe discussion part could be more detailed regarding the genesis of the sign with reference to the Einthoven triangle and probably an image depicting the same. Other corrections include “12-lead ECG” rather than “11-lead ECG” and the fact that the artefact arises not only from the radial artery but also from the posterior tibial artery (Takahashi K et al. 2023 [Ref - 2]).\nThe conclusion seems to be well done.\nOverall, the case report brings about a novel and rare ECG finding that is of utmost importance to be recognised in the emergency department, although the corrections and suggestions, if included would make it more productive.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "12828",
"date": "27 Nov 2024",
"name": "rabeb mbarek",
"role": "Author Response",
"response": "I would like to thank the reviewer for his precious time to read critically our case and for his important corrections suggested to improve the quality of our work. We tried to respond to all of your suggestions. Here is a response to each part of your report In the abstract section, the sentence regarding suspicious waveform contours with one completely normal limb lead appears to be repeated. The fact to exclude subjective assessments can be better framed for easy understanding : the sentence repeated was deleted The introduction section seems to be crisply constructed. Just one suggestion here would be to reframe the sentence as \"the artefact can be avoided by moving the lead away from the pulsating artery\": reformulated sentence In the case report section, the history seems enough. However, the necessary investigations that need to be done in such a case seem to be lacking or have not been provided by the authors. Since the Aslanger sign is seen in hyperdynamic conditions, it would have been informative if the authors had disclosed the relevant blood investigations to rule out hyperthyroidism, cirrhosis or severe anemia (Takahashi K et al. 2023 [Ref - 1]) and also considering the fact that the patient had a pulse pressure of 70mmHg, it would have been prudent to rule out aortic regurgitation by echocardiography: in blood investigations no cirrhosis or severe anemia were observed. an investigation for hyperthyroidism was not done but no history of hyperthroidism for our patient. an echocardiography was done in the emergency room without abnormality ( This part was added in our case report). A minor correction here would be “the abnormality was observed in all the leads except for lead III..” rather than \"11-lead ECG\" : correction done The discussion part could be more detailed regarding the genesis of the sign with reference to the Einthoven triangle and probably an image depicting the same. Other corrections include “12-lead ECG” rather than “11-lead ECG” and the fact that the artefact arises not only from the radial artery but also from the posterior tibial artery (Takahashi K et al. 2023 [Ref - 2]) : corrections done Best regards"
}
]
},
{
"id": "336519",
"date": "06 Nov 2024",
"name": "Koji Takahashi",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI believe that Aslanger's sign is still not well recognized, even by medical staffs working in cardiovascular and emergency medicine. Therefore, it is worthwhile to case report this typical case.\nThe abstract, introduction section, and case presentation section are good and concise.\nAs described by the authors, Aslanger's sign has a strange waveform spanning ST to TP segments in 11 out of 12 ECG inductions. Nevertheless, there is an obvious reason for its occurrence, and if there is no word limit, it would be better to describe it.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "12829",
"date": "27 Nov 2024",
"name": "rabeb mbarek",
"role": "Author Response",
"response": "I would like to thank the reviewer for his precious time to read critically our case and for this important corrections suggested to improve the quality of our work. corrections about references done . Best regards"
}
]
}
] | 1
|
https://f1000research.com/articles/13-1233
|
https://f1000research.com/articles/12-1597/v1
|
15 Dec 23
|
{
"type": "Research Article",
"title": "Acute effects of virtual reality exercise bike games on psychophysiological outcomes in college North-African adolescents with cerebral palsy: A randomized clinical trial",
"authors": [
"Makrem Soudani",
"Faical Farhat",
"Amine Ghram",
"Helmi Ben Saad",
"Mehdi Chlif",
"Makrem Soudani",
"Faical Farhat",
"Helmi Ben Saad",
"Mehdi Chlif"
],
"abstract": "Background Cerebral palsy (CP) is a neurological disorder that can affect motor skills and psychophysiological well-being. Virtual Reality Exercise (VRE) has been shown to improve cognitive and physical outcomes for patients with CP. Therefore, the aim of this study was to investigate the effects of VRE on attention, vigor, and decision-making abilities in adolescents with CP.\n\nMethods A randomized controlled trial was used. Fourteen Tunisian college adolescents (15.6 ± 0.7 years; diagnosed with CP) were randomly assigned to either the VRE group or the Traditional Exercise (TE) group. The VRE group engaged in 40 min exercise sessions using VRE bike games, while the TE group participated in TE sessions.\n\nResults Fourteen participants (42.9 % females) were included in this analysis The results showed that VRE had a significant positive impact on attention and vigor compared to TE. Participants in the VRE group demonstrated improved attention levels and reported higher levels of vigor following the exercise sessions.\n\nConclusions The findings suggest that VRE is an effective intervention for improving attention and vigor abilities in adolescents with CP. Further research is needed to confirm these findings and to investigate the long-term effects of VRE.\n\nRegistration Pan African Clinical Trial Registry (PACTR202308598603482; 31/08/2023).",
"keywords": [
"Cognitive Function",
"Decision-Making",
"Health",
"RCT",
"Training",
"Virtual Reality"
],
"content": "Introduction\n\nCerebral palsy (CP) is characterized by nonprogressive brain changes during fetal or infant development, leading to movement and posture abnormalities.1 In addition to motor disorders, patients with CP often exhibit symptoms related to sensory, cognitive, communicative, perceptual, behavioral, and seizure abnormalities.2 These patients are at an elevated risk of developing metabolic and cardiovascular diseases, as well as experiencing reduced cardiorespiratory endurance and muscle strength.3 Furthermore, they tend to engage in lower levels of physical activity (PA),4 which can contribute to negative health outcomes and premature mortality.5,6 As the most common cause of physical impairment, CP significantly impacts the quality of life, leading to substantial economic and psychological burdens.7\n\nTreatment approaches for CP are diverse and tailored to the type, severity, and individual needs of the patient.8 Physical therapy and rehabilitation are vital components of treatment, as they improve strength, flexibility, balance, motor development, and mobility.9 Furthermore, occupational therapy, speech and language therapy, along with adaptive equipment, can effectively address physical impairments and enhance mobility.10 To support emotional and behavioral challenges, psychologists and social workers can employ various strategies, such as behavior therapy, cognitive behavior therapy, strengths-based counseling, and mutual aid group work.11 These comprehensive and interdisciplinary interventions aim to provide holistic care and optimize the overall well-being of patients with CP.\n\nPhysical exercise plays a crucial role in the treatment of children/adolescents with CP.12 Physical exercise has significant implications for both short- and long- term health outcomes in CP, such as improved fitness levels, reduced risk factors for diseases, and fewer secondary complications.13 However, patients with CP tend to engage in less habitual PA compared to their peers, leading to adverse effects on their overall health and well-being.14 This lack of PA substantially increases the chances of developing obesity, cardiovascular diseases, and mental health problems.4 Therefore, clinicians should actively promote and facilitate opportunities for increased habitual PA while also encouraging a reduction in sedentary behavior, aiming to optimize long-term health outcomes.\n\nThe development of technology presents a promising avenue for promoting PA and overall well-being. Interactive video games, such as video game cycling, virtual reality (VR), and mobile games, have proven effective in encouraging individuals of all age groups to engage in, and increase their PA levels.15 VR, a form of digital technology that integrates sight, sound, touch, and smell to create an immersive experience, has gained significant attention.16 In 2023, VR applications are being developed and utilized in various clinically based fields, including rehabilitative and behavioral medicine.17,18 Notably, the introduction of commercially available VR exercise (VRE) equipment, such as the VirZoom—a VR-based exercise cycle compatible with the Oculus VR headset—has shown promise.19 VirZoom exercise bike is an efficient, enjoyable, and motivating tool for PA, particularly among college students.20 These findings suggest that health professionals can consider utilizing such technology to encourage PA participation across different populations. However, further extensive trials are necessary to confirm and determine the optimal utilization of this technology in promoting PA. In summary, technology including interactive video games and VR, holds potential as an effective means to promote PA and improve overall health. Future research should focus on validating and expanding upon the findings, establishing guidelines for incorporating this technology into PA interventions. Existing literature demonstrates that regular exercise significantly improves and maintains cognitive function and memory.21 However, the effects of acute or single bouts of exercise have not been extensively explored. Literature provides growing evidence that acute aerobic exercise has a small but positive impact on human cognitive function, mood, and memory.22,23 Despite these findings, there remains limited evidence-based research on the cognitive function of children and adolescents.24,25\n\nTherefore, the present randomized controlled trial (RCT) aimed to investigate the physiological and psychological outcomes of using the VirZoom VRE bike compared to traditional exercise (TE) bikes in North African college adolescents with CP. Given the entertaining and motivating nature of the VRE experience, we hypothesized that VR applications would lead to higher attention, memory, vigor, and decision-making abilities as the main outcomes in college adolescents with CP compared to TE. Additionally, we aimed to assess the impact of VRE on spasticity as the secondary outcome.\n\n\nMethods\n\nThe study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the local Ethics Committee of the High Institute of Nursing, University of Sfax, Tunisia (Protection Committee Approval Registration code: CPP SUD N 0388/2022), registered on the Pan African Clinical Trial Registry (identification number: PACTR202308598603482). Written informed consent was obtained from all the adolescents’ parents or legal guardians. Adolescents agreed verbally to participate in this study.\n\nThis study is a subgroup analysis within the ongoing RCT registered with the Pan African Clinical Trial Registry (identification number: PACTR202308598603482) on August 31, 2023. The RCT was conducted following the guidelines established by the CONSORT statement.26,62 Testing occurred between June and August 2023 at Sfax Association for the Care of the Physically Handicapped (Sfax, Tunisia). All procedures in the study adhered to the ethical standards of the institution and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical.27 The study received approval from the University Institutional Review Board and the local ethics committee of the High Institute of Nursing, University of Sfax, Tunisia (Protection Committee Approval in 25 January 2022 Registration code: CPP SUD N 0388/2022). Before commencing the study, adolescents aged 14 to 16 years, along with their parents or guardians, received an explanation of the test protocol.\n\nA convenience sample of 14 college students were recruited from the aforementioned association. To select the participants, the study’s inclusion criteria were disclosed to physicians, pediatric physiotherapy clinics, special educators, speech therapists, sociologists from the above-cited association, and ambulant care services. Potential participants were approached through the association staff and social workers. These professionals then recruited them to participate in the study.\n\nThe eligibility criteria for participant selection were as follows: i) Adolescent aged between 14 and 16 years, ii) Medical diagnosis of spastic CP confirmed by a pediatric neurologist; iii) Motor function classified at level I or II according to the Gross Motor Function Classification System (GMFCS V), iv) PA levels below the international norm (i.e., less than one hour daily at >5 metabolic equivalents (MET)), indicating moderate or vigorous intensity,28 v) Lack of regular sports participation (i.e., less than three sessions per week for 20 minutes or more), and vi) Reported issues with mobility in daily life or sports.\n\nExclusion criteria for participation in the study were: i) Engaging in a week of moderate to intense exercise exceeding 150 minutes per week; ii) GMFCS level III to V, iii) Behavioral issues that prevent participation in group activities or a movement disorder primarily dyskinetic or atactic in nature, iv) Recent surgery within the previous six months, v) Botulinum toxin treatment, and vi) Serial casting within the recent three months, or scheduled procedures during the intervention period.\n\nThe patients’ level of physical ability was categorized using the GMFCS V.29 GMFCS level I or II indicate independent walking for more than 12 months and the ability to ambulate for at least 10 meters with or without a gait-assistance device (walker or crutches). GMFCS level III to V precludes the use of the Oculus Quest handheld controller, moderate to severe intellectual disability, uncontrollable seizures, or conditions that make physical training dangerous (e.g., hip dysplasia, cardiac arrhythmia, or mitochondrial defects).\n\nMethod used to generate the random allocation sequence: Simple random allocation was used to generate the random allocation sequence. This means that each participant had an equal chance of being assigned to either the intervention group or the control group.\n\nType of randomization; details of any restriction (such as blocking and block size): No restriction was used in this study. This means that participants were not blocked or stratified in any way.\n\nMechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned: Sequentially numbered envelopes were used to implement the random allocation sequence. The envelopes were sealed until interventions were assigned. The allocation sequence was generated by the researcher (MS in the authors’ list). The latter also enrolled participants and assigned them to interventions.\n\nFigure 1 exposes the study protocol.\n\nTE: Traditional exercise. VRE: Virtual Reality Exercise.\n\nAnthropometric measurements, height, weight, and body mass index (BMI) were taken with patients wearing light clothing and no shoes. Patients underwent two 40-minute cycling sessions30 on two distinct days. A two-day interval separated the sessions, and they were conducted in a counterbalanced manner: (1) a VirZoom VRE bike and (2) a TE bike. Both bikes are Everfit BFK-500 Kaohsiung, Taiwan. Each session consisted of three conditions. The first was a five-minute period in which the participant lay down. This was followed by a 30-minute cycling period. The third condition was another period lying down for the remaining time. The Go-No-Go task19 and the Profile Of Mood States scale (POMS)31 were administered two days prior to each session as well as immediately afterwards. Heart rate (bpm), blood pressure (mmHg), Modified Ashworth Scale,32 and Montreal Cognitive Assessment (MoCA)33 scores were recorded immediately before and after each session.\n\nHeight was measured with a Harpenden 602VR stadiometer to the last complete 0.1 cm, and body composition was estimated using a multifrequency bioelectrical impedance analyzer (TBF-410GS, Tanita Co., Tokyo, Japan). This is a method validated against reference methods.34 The parameters collected in this study included weight, Body Mass Index, fat mass, and fat free mass.\n\nVirZoom’s VZfit offers a unique experience by combining a controller attached to the handlebars and a sensor on the bike crank. When used in conjunction with an Oculus Go virtual reality headset, it allows researchers to explore various virtual destinations while the participant is stationary on a bike.35\n\nDuring the study, patients played two 30-minute exercise sessions on the VirZoom VZfit, which features a variety of mini-games. The games chosen for the study were “Le Tour” and “Race Car,” both of which require players to pedal faster or slower to speed up or slow down, and to lean their body side to side to turn left or right. These games were observed to be the most intense, and were played with a pedal resistance set at a medium level.\n\nAll participants were asked to maintain a moderate level of exertion, with their heart rate ranging between 65% to 85% of their Age-predicted Maximal Heart Rate (ApMHR)36 as measured by a polar sensor monitor.\n\nTo create a training environment that was similar to traditional cycling and to reduce the environmental impact, patients in the study watched a virtual cycling video on television while using the Sparnod fitness sub-52 stationary bike. The VR cycling sessions were designed to achieve an exercise intensity equivalent to 65% to 85% of the ApMHR.36\n\nTo ensure uniform exercise intensity between the traditional and VR cycling sessions, participants were instructed to maintain their heart rate between 65% and 85% of their ApMHR, which was measured by the integrated heart rate monitor on the stationary bike during the traditional cycling session.\n\nThe Go/No-Go task is a response inhibition task where a motor response must either be executed or inhibited.37 During this task, and using PEBL (for Psychology Experiment Building Language) computer software, participants were required to watch a sequential presentation on computer of letters and respond to a target letter by pressing a button space of the keyboard.38 The presentation began with a 2 × 2 array with four stars (one in each square of the array). A single letter (P or R) was then presented in one of the squares for a duration of 500 milliseconds with an inter-stimulus interval of 1,500 milliseconds. In the first condition (P-Go), participants were asked to press a button in response to the target letter P and withhold their response to the non-target letter R. The ratio of targets to non-targets was 80:20. The first condition consisted of 160 trials. A second, reversal condition (R-Go) was then administered, and participants were now asked to make a response to the target letter R and withhold their response to the non-target letter P (the letter that they were initially conditioned to make a motor response to the task, while NoGo errors and RT to Go responses are considered as indicators of impulsivity.37\n\nThe Go/No-Go task is a computerized test that evaluates inhibitory control, a crucial component of cognitive assessment and self-regulation.39 During the task, participants respond by pressing a button when certain visual stimuli appear (Go trials) and withhold their response to other stimuli (No-Go trials), measuring their response inhibition. However, response inhibition can be difficult if No-Go trials are relatively rare, as Go responses become prepotent, meaning the system is biased to produce them. To ensure that inhibitory control is necessary, No-Go trials should make up less than 20% of the trials and each trial’s duration should be shorter than 1,500 ms.40 To interpret data from the Go/No-Go task, precision and reaction time are measured, performance is compared with established norms, and errors of commission and omission are analyzed. Examining these factors provides insight into the participant’s response inhibition and determines whether their performance falls within the expected range.40\n\nThe MoCA is a cognitive screening tool designed to detect Mild Cognitive Impairment (MCI) in the early stages of various neurodegenerative disorders.41 It is a 10-minute test that is more sensitive than other commonly used screening tools, such as the Mini-Mental State Examination, making it a reliable and valid tool for detecting MCI in clinical settings.42\n\nThe MoCA is composed of 30 questions that assess various cognitive domains, including orientation, executive functioning, memory, language, and visuospatial abilities.33 We used for this study the Arabic version. The tasks in the MoCA include naming objects, memorizing a short list of words, drawing a clock face, and performing serial subtraction tasks. Scores on the MoCA range from 0 to 30, with a cut-off point of 26, where a score of 26 or higher is generally considered normal.33\n\nThe measurement of mood can be obtained using a valid, reliable, and sensitive self-report questionnaire called the POMS,43 which consists of 58 items (i.e., words or sentences) and can provide valuable information about adolescents’ emotional states.44 We used the POMS Arabic version.45 The POMS is a self-report assessment tool that measures six dimensions of mood: Tension-anxiety, anger-hostility, vigor-activity, fatigue-inertia, depression-dejection and confusion-bewilderment.\n\nThe POMS is a 65-item questionnaire that is scored on a 5-point scale (0 = not at all to 4 = extremely).46 It takes about 10-15 minutes to complete.\n\nThe PACES is a reliable, valid and sensitive measure of PA enjoyment across populations.47,48 The Arabic version of the PACES, which has been reported to be a reliable and valid measure of enjoyment of PA in Arabic-speaking populations, was applied.49 The PACES consists of 18 items that are rated on a 7-point Likert scale, from 1 (I don’t enjoy it at all) to 7 (I enjoy it very much). The total score of the PACES ranges from 18 to 126, with higher scores indicating greater enjoyment of PA.\n\nThe MAS assesses spasticity by measuring resistance to passive joint movement in patients with neurological disorders.32 The scale assigns scores from 0 to 5 based on the degree of increased muscle tone, ranging from no increase (0) to severe increase (4). To conduct the assessment, patients are placed in a supine position, and for muscles primarily involved in flexion, the joint is moved from maximal flexion to maximal extension over one second, while muscles primarily involved in extension are moved from maximal extension to maximal flexion over one second. The investigator records the level of resistance encountered during the movement to determine the corresponding score: 0 for no resistance, 1 for minimal resistance at the end range, 1+ for a catch followed by less resistance over half the range, 2 for rigidity over more than half the range, and 3 for considerable resistance over most of the range. In this study, we have utilized the 0 to 5 version of the MAS50 to measure spasticity. The latter version enables numerical quantification of spasticity severity. During the assessment, the participants were placed in a supine position, and the investigators slowly flexed and extended each joint over one second, recording the amount of resistance encountered on the scale from 0 to 5.\n\nA priori power analysis was conducted using G*Power351 with the alpha level set at 0.05 and a power of 0.80, which concluded that the sample size to find significance should be 14 patients.\n\nValues were presented as the mean ± standard deviation (SD). Cohen’s effect sizes (d) were classified as small (0.20), moderate (0.50), and large (0.80).52 A 2 × 2 repeated-measures analysis of variance (ANOVA) was used to assess differences in, and between experimental trials. The two independent variables were exercise type and time. The two levels of the first independent variable (exercise type) were TE and VRE conditions. The two levels of the second independent variable (time) were pre and post-training.\n\nStatistical analyses were performed using the IBM SPSS version 26 (IBM SPSS, Chicago, IL, USA). Alpha level was set at p<0.05.\n\n\nResults\n\nAmong the initial 20 patients, only 14 were included in the final sample (7 in each group) (Figure 2).61\n\nn: number. TE: Traditional exercise. VRE: Virtual Reality Exercise.\n\nTable 1 exposes the demographic characteristics of the 14 patients.\n\nTable 2 exposes the comparison of pre- and post-training scores for attention, memory, total score, vigor, decision making correct and decision making errors in both the TE and VRE training conditions.\n\nThere was a significant main effect of exercise type on patients’ attention (F (1,13) = 6.30, p = 0.026, ηp2 = 0.327). Patients’ mean response attention was higher in VRE (SD = 1.25137) compared to TE (SD= 1.15073). This difference was a significant main effect of time F (1.13) = 97.066, p = 0.001, ηp2 = 0.882). Patients’ mean response attention was higher at post-training (SD = 0.615) compared to pre-training (SD = 1.251). There was a statistically significant interaction between exercise type and time (F (1.13) = 6.30, p = 0.026, ηp2 = 0.327).\n\nThere was a significant main effect of exercise type on patients’ memory (F (1.13) = 3.059, p = 0.104, ηp2 = 0.190). Patients’ mean response memory were higher in TE (SD= 0.662) compared to VRE (SD = 0.864). This difference was a significant main effect of time F (1.13) = 180.974, p = 0.001, ηp2 = 0.933). Patients’ mean response memory were higher at pre-training (SD = 0.928) compared to post-training (SD = 0.864). There was a statistically significant interaction between exercise type and time F (1.13) = 3.59, p = 0.104, ηp2 = 0.190).\n\nThere was a significant main effect of exercise type on patients’ total scores (F (1.13) = 19.118, p = 0.001, ηp2 = 0.595). Patients’ mean response total score were higher in VRE (SD = 2.547) compared to TE (SD = 2.841). This difference was a significant main effect of time F (1.13) = 80.686, p = 0.001, ηp2 = 0.861). Descriptive statistics revealed that patients’ mean response attention was higher post-training (SD = 2.547) compared to pre-training (SD= 2.334). There was a statistically significant interaction between exercise type and time F (1.13) = 19.118, p = 0.001, ηp2 = 0.595).\n\nThere was a significant main effect of exercise type on patients’ vigor (F (1.13) = 2.576, p = 0.133, ηp2 = 0.165). Patients’ mean response vigor were higher in VRE (SD =2.248) compared to TE (SD= 7.500). This difference was a significant main effect of time F (1.13) = 1.320, p = 0.271, ηp2 = 0.092). Descriptive statistics revealed that patients’ mean response vigor were higher at post-training (SD = 2.248) compared to pre-training (SD = 3.989). There was a statistically significant interaction between exercise type and time F (1,13) = 2.576, p = 0.133, ηp2 = 0.165).\n\nThere was a significant main effect of exercise type on patients’ decision-making (F (1.13) = 26.338, p = 0.01, ηp2 = 0.670). Patients’ mean response decision making correct were higher in VRE (SD = 11.486) compared to TE (SD = 19.917). This difference was a significant main effect of time F (1,13) = 3.833, p = 0.72, ηp2 = 0.228). Patients’ mean response attention were higher at post-training (SD = 11.48649) compared to pre-training (SD = 19.91700). There was a statistically significant interaction between exercise type and time F (1,13) = 27.611, p = 0.001, ηp2 = 0.680).\n\nThere was a significant main effect of exercise type on patients’ decision-making errors F (1,13) = 28.202, p = 0.001, ηp2 = 0.684). Patients’ mean response decision-making errors were higher in TE (SD= 20.299) compared to VRE (SD = 13.589). This difference was a significant main effect of time F (1,13) = 5.350, p = 0.038, ηp2 = 0.292). Patients’ mean response decision-making errors were higher at pre-training (SD= 21.15770) than post-training (SD= 13.58995). There was a statistically significant interaction between exercise type and time F (1,13) = 27.045, p = 0.001, ηp2 = 0.675).\n\nTable 3 exposes the comparison of pre- and post- training scores for spasticity in both the TE and VRE training condition. Both TE and VRE interventions effectively reduced spasticity levels in various lower body regions. Notably, the VRE group exhibited more substantial improvements, with a 5.61 reduction in spasticity for the lower body (ankle + knee) compared to TE’s 3.28. In the ankle region, VRE resulted in a significant 2.29 reduction in spasticity, while TE achieved a reduction of 1.43.\n\n\nDiscussion\n\nThe present study aimed to investigate the effectiveness of VRE in improving the psychophysiological outcomes of college-aged patients with CP. Our RCT demonstrated that VRE had a significant positive impact on attention, as indicated by higher scores when compared to TE. Furthermore, VRE yielded slightly higher scores in increasing patients’ vigor than TE. In terms of decision-making, a significant main effect of exercise type was observed, with VRE leading to higher scores than TE. However, it is worth noting that TE resulted in higher memory scores than VRE.\n\nWe found that VRE immediately following PA might have a more favorable impact on attention compared to TE. This finding is in line with prior research demonstrating the ability of VR to enhance cognitive function, particularly attention, and cognitive training’s potential to improve daily activities.53 Additionally, this aligns with Neumann et al.54 discovery that VR may not always be the optimal approach for diverting attention from exercise-related cues, emphasizing the importance of attentional mechanisms in shaping emotional and motivational responses to exercise in a VR environment. By directing attention towards the virtual environment, VR systems can increase the likelihood of positive impact and satisfaction, underscoring the crucial role of attentional mechanisms in shaping emotional and motivational responses during VRE. According to a 2020 research, VR environments can be customized to simulate real-life situations that require specific cognitive abilities, such as memory, decision-making, and problem-solving.53 Our study investigated the acute effects of VRE on memory and compared it to TE. Our findings reveal a significant difference in memory scores between pre- and post- training, suggesting that time has a considerable impact on patients’ memory. Interestingly, the memory scores varied significantly between the TE and VRE conditions, with patients’ mean response memory being higher for TE than VRE. However, the interaction between exercise type and time was not significant, indicating that the impact of exercise type on memory did not depend on whether the memory was measured before or after the exercise. Our results differ from previous research on memory in elderly stroke survivors, which suggests that training environments can be customized to improve cognitive abilities, including memory, that influence daily activities.53 Additionally, the study’s results highlight the potential benefits of immersive VR in facilitating the transfer of learned abilities from the virtual world to the real world. While some studies suggest that VRE may not be as effective as TE in enhancing memory, other studies have identified that VRE can be helpful in reducing memory decline in older adults.55 Further research is necessary to confirm these findings and identify the potential advantages of exercise for memory enhancement. Therefore, the potential benefits of VRE for memory enhancement warrant further investigation.\n\nThere is evidence to suggest that there is a link between attention, memory, and vigor after immediate exercise. We report a significant main effect of exercise type on vigor, with patients reporting higher levels of vigor after VRE compared to TE. Moreover, there was a significant main effect of time on patients’ vigor, with higher levels of vigor reported after the exercise compared to before the exercise. However, there was no significant interaction between exercise type and time on patients’ vigor. Our findings are consistent with previous research indicating that acute exercise can enhance feelings of vigor in the short term.27 However, our results did not align with the findings of Adhyaru et al.,56 who reported no significant difference in vigor between VRE and TE.\n\nWe identified a significant main effect of exercise type on patients’ decision-making, with higher scores observed in VRE compared to TE, suggesting that VRE may enhance decision-making abilities. However, no significant main effect of time on decision-making scores was found, indicating that the effect of exercise on decision-making did not differ significantly between pre- and post- exercise measures. Our finding diverges from previous studies that reported improvements in decision-making following acute exercise, such as Ulas et al.57 study that found a single bout of moderate-intensity exercise improved decision-making performance in healthy adults. Our result is consistent with Shaw et al.58 study, which reported that the use of a competitive virtual trainer while riding at a moderate-vigorous intensity did not improve cognitive performance. Conversely, our findings align with those of Ertoy Karagol et al.59 who reported that VRE led to a significant improvement in vigor compared to the control group, as well as a significant increase in PA compared to the control group. These results suggest that VRE may be an effective intervention for improving vigor and PA in adolescents.\n\nFurthermore, the interaction effect between exercise type and time indicated that the style of exercise and the measurement time had different effects on decision-making abilities. Thus, further investigation, such as post-hoc tests, is necessary to identify conditions that significantly varied from one another.\n\nOur study identified significant differences in decision-making errors based on exercise type and time, indicating both have an impact. Patients made more errors during TE vs. VRE, suggesting VR provides greater cognitive benefits for decision-making. Moreover, patients made fewer errors post-training, showing exercise overall reduces decision-making errors. The significant interaction between exercise type and time demonstrated the effect of exercise on errors differed pre- and post- exercise. Benefits of VRE on errors seemed more pronounced post-training, while benefits of TE were less evident. Overall, these findings suggest that VRE may be more beneficial than TE for improving decision-making accuracy and that the effects of exercise on decision-making may vary depending on the type of exercise and timing of assessment. Our findings that VRE may be more advantageous than normal exercise for enhancing decision-making accuracy is supported previous study.60 Mestre et al.60 compared indoor cycling exercise with VR feedback vs. non-VR feedback and highlighted that cycling exercise with VR feedback had a reduced perceived exertion and an increased level of enjoyment of PA. This finding unequivocally demonstrates the beneficial effects of VR feedback and a virtual coach on the enjoyment of PA, with the virtual coach showing the greatest gains.60\n\nOur results indicate that VRE with bike has the potential to acutely reduce muscle spasticity. VRE with bike provide visual and auditory stimulation in addition to cycling, which may distract users and draw attention away from muscle sensations.30 In turn, this reduction in sensory input could decrease muscle spasms and contractions, resulting in temporary relief from spasticity.56 The immediate effects observed after using the VRE bike30 suggest an acute impact on spasticity. However, longer-term investigations are needed to determine whether regular use of VRE with bike can yield sustained benefits for reducing spasticity.30\n\nThese results emphasize the potential advantages of incorporating VRE as a promising intervention, with larger effect sizes, to enhance the physical well-being and motor skills of individuals with CP in this demographic.\n\nSome potential limitations must be considered. The major limitation concerns the retrospective registration of our RCT. The main reason of the retrospective registration is the lack of experience of the first author (MS in the authors’ list). During the study execution, when he asked help from senior authors, they recommended to register the study. Since the primary purpose of trial registration is to enhance transparency, reduce bias, and promote the integrity of clinical research, a retrospective registration of an RCT can pose some challenges and may be viewed with skepticism by journal editors, peer reviewers, and readers. When an RCT is registered retrospectively, it can raise concerns about selective reporting, outcome switching, and potential bias. However, we have registered our RCT in the aim to be transparent about the timeline of the study. The registration was done as soon as possible just before the end of the trial. We have included the full study protocol with detailed information on the study design, primary and secondary outcomes, and statistical analysis plan. This demonstrate that our study was conducted in a rigorous and pre-planned manner. We confirm that our study adheres to ethical guidelines and that the retrospective registration does not compromise the ethical conduct of the trial. We have explicitly discussed how we have mitigated the risk of bias in our study, by addressing concerns related to selective outcome reporting and data-driven decisions. We attest that there was no modifications to the study design or analysis plan after data collection. Second, the study’s short duration precludes conclusions about prolonged effects. Third, the small sample size may limit generalizability. Finally, potential confounding factors such as patients’ exercise history and spasticity severity were not considered. Despite these limitations, our study has enhanced our understanding of the relationship between TEs and virtual one for adolescents with CP. We think that our findings will stimulate further investigation of this important area.\n\nFor adolescents with CP, VRE bike games using VirZoom’s VZfit appear to be a fun, effective alternative to boost adherence and consequently enhance mood. Future studies should be conducted in this regard to investigate additional topics related to VRE bike games for children, including assessing those with CP using objective measures to determine how long the virtual headset workouts last; assessing the interactions between individual and group activities; and determining the long-term effects of the activities performed both in the lab and at home.\n\n\nConclusions\n\nVRE can help improve attention, vigor, and decision-making in college students with CP more than TE. However, TE may be more beneficial for enhancing memory scores. Future research with larger samples is needed to validate our findings and identify the mechanisms driving differences in cognitive outcomes between VR and TE. Overall, both types of exercise show potential for improving mental performance and wellbeing.",
"appendix": "Data availability\n\nZenodo: Data of 14 participants in the RCT titled Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy. https://doi.org/10.5281/zenodo.10201736. 61\n\nZenodo: CONSORT checklist for: Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy: A randomized Clinical trial. https://doi.org/10.5281/zenodo.10157607. 62\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThe authors would like to thank the adolescents and their parents. Open Access funding provided by Qatar National Library.\n\n\nReferences\n\nRosenbaum P, Paneth N, Leviton A, et al.: A report: the definition and classification of cerebral palsy April 2006. Dev. Med. Child Neurol. Suppl. 2007; 109: 8–14. 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Inform. 2011; 167: 122–127.\n\nSoudani M: Data of 14 participants in the RCT titled Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy. [Dataset]. Zenodo. 2023. (Last Visit: November 23, 2023). Publisher Full Text\n\nSoudani M, Farhat F, Ghram A, et al.: CONSORT checklist for: Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy: A randomized Clinical trial. Zenodo. 2023. (Last visit: November 20, 2023). Publisher Full Text"
}
|
[
{
"id": "248808",
"date": "29 Mar 2024",
"name": "Qamar Mahmood",
"expertise": [
"Reviewer Expertise Pediatric rehabilitation specifically in the management of Cerebral Palsy",
"Physical therapy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article investigated the immediate effects of virtual reality exercise (VRE) bike games on young adults in North Africa with cerebral palsy (CP). Its brief description is as under:\nStudy Design: Randomized controlled trial (considered a gold standard for clinical research) Participants: 14 college students (average age 15.6) diagnosed with CP Intervention: Participants were divided into two groups. One group exercised using VR bike games for 40 minutes (VRE group), while the other group participated in traditional exercise (TE group) for the same duration. Outcomes: The study measured changes in attention, vigor (energy levels), and decision-making abilities after the exercise sessions. Key Findings: Compared to traditional exercise, VR exercise led to significant improvements in attention and vigor.\nIts Clinical Relevance: Cerebral palsy can impair both physical function and mental well-being. This study suggests VR exercise could be a valuable tool for improving cognitive function and motivation in young adults with CP. VR's engaging nature might make exercise more enjoyable and help individuals with CP adhere to exercise routines. However, it's important to note that the study only looked at short-term effects. More research is needed to confirm these findings and explore the long-term benefits of VR exercise for CP management. This article is well written, however following major and minor changes will improve its quality for publication. Minor Changes needed:\nIn abstract section; Briefly mention the mixed findings on memory to provide a more balanced picture of the results.\n\nIn introduction section: Emphasize the novelty and significance of the present study. Instead of stating existing knowledge about the benefits of regular exercise, briefly mention the limited research on the effects of acute exercise on cognitive function in adolescents with CP, highlighting the gap your study aims to address. Consider reorganizing the information flow. Start by highlighting the gap in knowledge about acute exercise and cognitive function in adolescents with CP. Then, briefly mention the existing evidence of VR's effectiveness in promoting physical activity, leading to the introduction of the VirZoom VRE bike and the research question. Briefly define psychophysiological outcomes for the audience unfamiliar with these terms.\n\nIn methodology section: Further emphasize the novelty of using VirZoom VRE compared to traditional exercise bikes in this specific population (adolescents with CP). Briefly explain the rationale behind choosing specific games on the VirZoom VRE for the study.\nMajor Changes needed:\n\na-In result section, please make following changes.\nDemographic characteristics should be presented as group wise. Because you have two groups, therefore, split age, gender etc. group wise. You can make three groups as TE, VRE and Total study population too. Mention the name of statistical test which you have used in stats of Table-2. You have mentioned that significant changes took place in Vigor too which is not the case as per stats of the study. Correct this. Mention the age in months instead of years because it sounds better. How many readings of MAS were taken on a particular joint? Why have you not used the mean of readings for MAS which is established practice in literature? Table -3 lacks the significance level (p value). Where is it? In absence of statistical significance, how can you claim that changes are significant?\n\nb-In discussion section; please make following\n\nchanges.\nDon’t use the words our, I, my in research writings. Instead of our study, you can say present study or current study. Similarly instead of we found, you can write, results exhibits etc. While acknowledging limitations, the discussion could be strengthened by using more cautious language when describing the potential benefits of VRE, especially in areas where the findings are mixed or inconclusive. If possible, the discussion could be strengthened by delving deeper into the possible mechanisms by which VRE might be exerting its effects on various outcomes.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12675",
"date": "27 Nov 2024",
"name": "Amine Ghram",
"role": "Author Response",
"response": "Reviewer Comment 1: In the Abstract section, briefly mention the mixed findings on memory to provide a more balanced picture of the results. Response: We appreciate your insightful comments. Presenting a more balanced view of results, particularly regarding memory, is crucial for accuracy and transparency. The abstract has been revised to reflect heterogeneous findings on memory, ensuring that it aligns with the overall outcomes of the study. Action Taken: The following statement was incorporated into the abstract (lines 33–37):’ Fourteen participants (42.9% female) were included in this analysis, and the results indicated that VRE had a statistically significant positive effect on attention and vigor compared to TE. While participants in the VRE group exhibited enhanced attention levels and reported elevated levels of vigor subsequent to the exercise sessions, the memory results did not reach statistical significance.\" This modification ensures a comprehensive interpretation of the findings and prepares readers for the study's conclusions. Reviewer Comment 2: In the introduction section, emphasize the novelty and significance of the present study. Instead of stating existing knowledge about the benefits of regular exercise, briefly mention the limited research on the effects of acute exercise on cognitive function in adolescents with CP, highlighting the gap your study aims to address. Response: Thank you for your constructive feedback. To emphasize the novelty and significance of our investigation, we restructured the introduction to focus on the limited research on the effects of acute exercise on cognitive function in adolescents with cerebral palsy (CP). This modification highlights the research gap that our study addresses and underscores the unique contribution of our work to the field. Action Taken: The following passage was incorporated into the introduction (lines 71–78):’ This study represents a significant advancement in elucidating the relationship between acute exercise and cognitive function in adolescents with CP. Despite extensive research demonstrating the benefits of regular exercise on cognitive health, there remains a notable gap in our understanding of how a single bout of exercise affects cognitive function in this specific population. This study was motivated by a growing body of evidence suggesting that acute aerobic exercise positively influences cognitive function, mood, and memory in various populations. However, these effects remain relatively unexplored in children and adolescents, particularly those with CP. This gap underscores the need for targeted research to elucidate how acute exercise can be utilized to enhance cognitive outcomes in this vulnerable population.\" This addition enhances the novelty of our study and elucidates how our research addresses a gap in the literature in accordance with the reviewer's recommendation. Reviewer Comment 3: Consider reorganizing the information flow. Start by highlighting the gap in knowledge about acute exercise and cognitive function in adolescents with CP. Then briefly mention the existing evidence of VR's effectiveness in promoting physical activity, leading to the introduction of the VirZoom VRE bike and the research question. Response: We acknowledge your comprehensive feedback regarding the structure of the Introduction. In accordance with your recommendation, we have restructured the introduction to initially address the gap in current knowledge concerning acute exercise and cognitive function in adolescents with cerebral palsy (CP), subsequently transitioning to existing evidence on virtual reality (VR) as a modality for promoting physical activity. This revised organization enhances the clarity of the narrative and establishes a logical progression towards the introduction of the VirZoom VRE bike and the research question. Action Taken: The introduction now commences with a discussion of the limited research on acute exercise and cognitive function in adolescents with CP, followed by a brief mention of VR's effectiveness of VR (Lines 96–103). \" This study represents a significant advancement in understanding the impact of technology, specifically virtual reality (VR), on the well-being of adolescents with cerebral palsy (CP). Although previous studies have established the benefits of regular physical activity in adults with CP, there is a paucity of data regarding the immediate effects of exercise, particularly on cognitive performance, in adolescents with CP. The objective of our randomized controlled trial (RCT) was to compare the physiological and psychological effects of using the VirZoom VR exercise cycle with traditional exercise (TE) bicycles among university students with CP in North Africa. This study aimed to examine the impact of acute exercise on cognitive function, affection, memory, and decision-making abilities. This research contributes valuable insights into a critical topic that has received limited attention in this specific population.\" This reorganization provided a more coherent rationale for the study and more effectively established the context for the research question. Reviewer Comment 4: Briefly define psychophysiological outcomes for the audience unfamiliar with these terms. Response: We appreciate your recommendation. It is acknowledged that the term \"psychophysiological outcomes\" may not be familiar to all readers; therefore, a concise definition has been incorporated to enhance comprehension for a broader audience. Action Taken: The following definition has been incorporated (lines 53–56):’ Psychophysiological outcomes refer to the observable effects of psychological processes on the physiological functions of the body (8). Psychophysiology is the scientific study of how cognitive processes, emotional states, and behaviors influence physiological responses, including heart rate, blood pressure, hormone levels, and brain function (9).\" This succinct definition ensures that all readers, irrespective of their expertise, comprehend this crucial term and its significance to this study. Reviewer Comment 5: In the methodology section: Further emphasize the novelty of using VirZoom VRE compared to traditional exercise bikes in this specific population (adolescents with CP). Response: We acknowledge your feedback and concur that it is essential to emphasize the novelty of the VirZoom VRE system, particularly its application in adolescents with CP. The utilization of immersive VR technology in exercise interventions for this population represents a relatively nascent area of research, and we have elucidated this novelty more explicitly in the methodology section. Action Taken: We revised the methodology section to include the following statement (Lines 128–152):’ it is essential to emphasize the novelty of implementing the VirZoom VRE system in comparison to TE bikes, particularly within the context of adolescents with CP. Although TE bikes have been utilized in numerous rehabilitation settings, the integration of VR technology represents an innovative approach to increase physical activity and improve health outcomes in this specific population. The VirZoom VRE system provides a unique and immersive fitness experience that transcends the limitations of conventional stationary cycles by offering users dynamic virtual environments to explore during exercises. This novel approach not only introduces an element of enjoyment and engagement in the training program, but also presents opportunities for cognitive stimulation and social interaction, which are particularly beneficial for adolescents with CP. Furthermore, the VirZoom VRE system enables customizable training protocols and game-based activities to address the diverse needs and abilities of individuals with CP. By incorporating games that target specific muscle groups, movement patterns, and cognitive skills, we can tailor the exercise experience to align it with the individual rehabilitation objectives and interests of our participants. By emphasizing the novelty of implementing the VirZoom VRE system in this study, we underscore its potential to transform the delivery of physical activity interventions for adolescents with CP, ultimately leading to improved health outcomes and enhanced quality of life for this population. The selection of specific games in the VirZoom VRE system for our study is based on several rationales. Primarily, we aimed to ensure that the chosen games offered a diverse range of physical activities that engaged various muscle groups and movement patterns, addressing the heterogeneous needs and abilities of adolescents with CP. Second, we prioritized games that are immersive, interactive, and engaging, as research indicates that the entertainment value of VR experiences can significantly influence exercise adherence and participation. Additionally, we considered the cognitive demands of each game, selecting those that incorporated elements of attention, memory, decision-making, and problem solving to potentially enhance cognitive outcomes in our participants (31). Lastly, we aim to incorporate games that facilitate social interaction and competition, fostering a sense of camaraderie and motivation among participants, which may further contribute to the efficacy of the intervention.\" This explanation emphasizes the innovative nature of the intervention and its potential benefits, thereby elucidating the study's contribution to the field. Major Changes needed: a-In the result section, please make following changes. Response to Reviewer’s Comment We appreciate the reviewer’s suggestion to present demographic characteristics in a group-wise format. This change enhanced the clarity and comprehensibility of the participants’ data. Action Taken: We created a new Table 1 that presents the demographic characteristics for each group (TE, VRE) as well as for the total study population. The table is formatted as follows. Table 1: Demographic Characteristics of Participants (refer the below link) https://f1000research.s3.amazonaws.com/linked/685666.Table_1_Demographic_Characteristics_of_Participants.pdf This table enhances the presentation of demographic data and provides a clearer comparison between the groups in accordance with the reviewer's recommendations. Reviewer Comment 6 • Mention the name of the statistical test that you have used in stats in Table-2. Response: Thank you for your valuable feedback regarding the statistical analysis of our study. You are correct that we should have explicitly mentioned the statistical tests used for the results presented in Table 2. We appreciate your attention to detail and opportunity to clarify this important aspect of our methodology. Action Taken: We have revised the manuscript to include the specific statistical tests used for the analysis presented in Table 2. The statistical method has been added to the \"Statistical analysis\" section of the Methods and referenced in the table caption. Text added in text: line number 283-291 in bold\" A 2 × 2 repeated-measures ANOVA was conducted to examine the effects of exercise type (Traditional Exercise vs. Virtual Reality Exercise) and time (Pre vs. Post) on performance scores. Data were analyzed using SPSS version 28.0. Prior to analysis, Mauchly's test of sphericity was performed to assess the assumption of sphericity. If Mauchly's test was significant, indicating a violation of sphericity, the degrees of freedom were corrected using the Greenhouse-Geisser or Huynh-Feldt corrections, as appropriate. Main effects and interactions were evaluated, and post hoc tests were conducted using the Bonferroni correction to further explore the significant effects. Descriptive statistics, including means and standard deviations for each condition, were calculated to provide a comprehensive understanding of the data. Statistical significance was set at an alpha level of .05 for all analyses.).\"Additionally, we updated the caption for Table 2 : line number 308 in \"Table 2. Comparison of pre- and post-training scores for attention, memory, total score, vigor, correct decision making, and decision-making errors in both the TE and VRE training conditions using 2 × 2 repeated-measures ANOVA.\"We believe that these additions have clarified the statistical method used and addressed your concerns. The use of repeated-measures ANOVA is appropriate for our study design as it allows us to examine the effects of both exercise type and time, as well as their interaction, on our outcome measures. Reviewer Comment 7 • You have mentioned that significant changes took place in Vigor, too, which is not the case as per the stats of the study. Correct this. Response: Thank you for your valuable feedback regarding the reporting of vigor results. We appreciate your detailed attention. Upon re-evaluation of the statistical analysis, we corrected the manuscript to remove any references to significant changes in vigor. Action Taken: The updated text accurately reflects that the analysis did not indicate significant changes in vigor, according to the statistical results. The previous statement, \"significant changes were observed in vigor,\" has been removed and replaced with \" Exercise type had no significant changes on patient vigor.\" This correction can be found in the revised manuscript in the Results section (line 132). We have made necessary revisions to ensure clarity and accuracy in reporting the findings. Thank you for helping us improve the quality of our manuscript. Reviewer Comment 8 • Mention the age in months instead of years because it sounds better. Response: Thank you for your suggestion regarding the reporting of participants' ages. We appreciate your attention to the details and your recommendations to enhance the precision of our demographic data. Action Taken: We have revised the manuscript to report participants' ages in months instead of years. Specifically, in the Results section, line 306, we have changed \"15.6 ± 0.7 years\" to \"163.57 ± 41.58 months. This modification provides a more precise representation of the participants' ages and aligns with the best practices for reporting developmental data for adolescent populations. We believe that this change has improved the clarity and accuracy of our demographic information. Thank you for helping us enhance the quality of our manuscript. Reviewer Comment 9 • How many readings of MAS were taken on a particular joint? Why have you not used the mean of readings for MAS which is established practice in literature? Response: Thank you for your insightful comments regarding the measurement of the Modified Ashworth Scale (MAS) readings. We appreciate your attention to methodological rigor. Action Taken: In the revised manuscript, we have clarified that three readings of the MAS were taken for each joint to ensure reliability and accuracy. To adhere to established practices in the literature, we calculated and used the mean of these readings in our analysis. This adjustment is reflected in the Methods section, specifically on line 278, where we now state that \"The mean of three MAS readings was used for each joint assessment.\" We believe that this change enhances the validity of our findings and aligns our methodology with the standard practices in the field. Thank you for your valuable feedback, which has helped us improve the quality of our manuscript. Reviewer Comment 10 • Table -3 lacks the significance level (p value). Where is it? In absence of statistical significance, how can you claim that changes are significant? Response: Thank you for your valuable feedback regarding Table 3. We appreciate your attention to the details and emphasize the importance of statistical significance in reporting the results. Action Taken: We updated Table 3 to include the significance levels (p-values) for all reported outcomes. This clarifies the statistical significance of the changes observed in the present study. Specifically, we have added p-values in the last column of Table 3, which can be found in the revised manuscript. Moreover, we have revised the text to ensure that any claims of significance are supported by the corresponding statistical outcomes, which enhances the transparency and rigor of our results, aligning our reporting with best practices in the literature. Thank you for your constructive suggestions, which helped us improve the quality of our manuscript. Reviewer Comment 11 b-In discussion section; please make following changes. Reviewer Comment 12 • Don’t use the words our, I, my in research writings. Instead of our study, you can refer to the present study or the current study. Similarly instead of we found, you can write, results exhibits etc. Response: We appreciate your feedback regarding the use of personal pronouns in research writing. We agree that maintaining an objective tone is important in scientific communication. Action Taken: We have carefully reviewed the entire manuscript and made the following changes: Replaced \"our study\" with \"the present study\" the present study’ throughout the document. Changed, \"we found\" to \"results exhibit\" where applicable. Replaced \"we suggest\" with \"the current study suggests\" as appropriate. Removed all instances of \"I\" and \"my\" from the manuscript. These revisions can be found throughout the document, particularly in the Results section and Discussion section.We believe that these changes have improved the objectivity and professionalism of our writing, while maintaining clarity. Thank you for helping us enhance the quality of our manuscript. Reviewer Comment 13 • While acknowledging the limitations, the discussion could be strengthened by using more cautious language when describing the potential benefits of VRE, especially in areas where the findings are mixed or inconclusive. Response: Thank you for your valuable feedback regarding the language used to discuss the potential benefits of Virtual Reality Exercise (VRE). We appreciate your emphasis on the importance of using cautious language, especially when addressing areas with mixed or inconclusive findings. Action Taken: In response to your comment, we have thoroughly revised the discussion section to incorporate a more nuanced and careful approach in describing the potential benefits of VRE. Specifically, we have: Emphasizing the need for further research by stating that while some findings suggest benefits, it is crucial to recognize that other studies present mixed results. This balanced perspective is vital for accurately conveying the current state of the literature. We acknowledge the limitations of our study in terms of the generalizability of the findings. We explicitly state that additional evidence is necessary to substantiate the claims made regarding VRE, ensuring that our conclusions are firmly grounded in the available data. Utilizing cautious phrases such as \"may suggest\" and \"could potentially contribute\" could potentially contribute’ instead of making definitive statements. For instance, we have replaced \"VRE improves cognitive function\" with \"VRE may improve cognitive function,\" effectively communicating the tentative nature of our findings. We believe these changes enhance the rigor and credibility of our discussion, providing a more accurate representation of the potential benefits of VRE while also emphasizing the need for further research in this area. Thank you for your constructive feedback, which has been instrumental in improving the quality and integrity of our manuscript. Reviewer Comment 14 If possible, the discussion could be strengthened by delving deeper into the mechanisms through which VRE might exert its effects on various outcomes. Response: We appreciate your insightful comment regarding the potential mechanisms by which virtual reality exercises (VRE) may influence various outcomes. Your suggestion to deepen the exploration of these mechanisms in the discussion is highly valued. Action Taken: In response to your feedback, we have significantly expanded the discussion section to offer a more comprehensive analysis of the mechanisms underlying the effects of VRE. The specific revisions are as follows. Discussion of Engagement and Motivation: We elaborated on the role of VRE in enhancing participant engagement through immersive experiences, which can lead to increased motivation and adherence to exercise programs. For instance, we revised line 352 from \"VRE can increase motivation\" to \"The immersive nature of VRE may lead to heightened motivation, which is essential for improving physical activity levels.\" Exploration of Cognitive Function: We have included a detailed discussion on how VRE may facilitate cognitive engagement by requiring participants to interact with dynamic environments. In line 360, we modified the text from \"VRE may help cognitive function\" to \"VRE potentially stimulates cognitive function by challenging participants to make quick decisions and adapt to changing virtual scenarios.\" Highlighting Social Interaction Effects: We addressed the potential of VRE to promote social interaction and support, which could further enhance its effectiveness. In line 375, we revised the statement from \"VRE can be done alone or with others\" to \"Engaging in VRE in a group setting may foster social bonds, providing psychological benefits that contribute to overall well-being.\" Consideration of Physiological Responses: Finally, we examined the physiological responses associated with exercise in a virtual environment, positing that increased heart rate and caloric expenditure may arise from the interactive nature of VRE. We updated line 385 from \"VRE involves physical activity\" to \"The interactive features of VRE may elicit greater physiological arousal, potentially leading to enhanced cardiovascular benefits.\" These enhancements are reflected in the discussion section, particularly between lines 350 and 390, where we now present a well-rounded perspective on the mechanisms through which VRE may exert its effects on various outcomes. Incorporating these insights significantly strengthens the discussion and provides a more thorough understanding of the potential benefits of VRE. We are grateful for your valuable feedback, which has contributed greatly to the improvement of our manuscript."
}
]
},
{
"id": "237583",
"date": "30 May 2024",
"name": "Hsiu-Ching Chiu",
"expertise": [
"Reviewer Expertise My past research program was in understanding the relative contribution of motor impairments to activity limitation and participation in people with hemiplegic cerebral palsy (CP). I have finished one Cochrane review entitled as “Mechanically assisted walking training for walking",
"participation",
"and quality of life in children with cerebral palsy” for children with CP by examining outcomes across all domains of the International Classification of Functioning",
"Disability and Health (ICF)."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral comments\nThe topic under investigation is interesting, but there are some fundamental problems, such as the design of intervention. Furthermore, authors should improve the format of the presentation, suggesting having an example of published RCT paper to follow.\nAbstract. Not clear because of no information about the intervention such as weeks.\nIntroduction-content Not read because method is very confusing.\nMethods: general -Ethics considerations have been already mentioned in the design, so it would be unnecessary to repeat. -Randomization should be part of design, not separate paragraph.\nMethods: design Even this study has been registered, authors still need to provide information about design, such as training and outcomes etc.\nMethods: Figure 1 Authors should show how many weeks of intervention as well as a brief content for both groups.\nMethods: participants -should use “Participants” to replace “Patients”. -Actual number of participants and characteristics should be in the results.\nMethods: Intervention This is main problem because it’s hard to believe it will be effective for only 2 times training.\nResults: Table 1 (missing). Characteristic of participants Results: Table 2 (missing).Differences between groups in all Outcomes across times\nDiscussion and conclusion: Not read because method and results are very unstructured.\nReadability and style. This paper is not easy to read, because of unstructured and the fluency of English. For example, “….in adolescents with CP in North African college….” Not “In North African college adolescents with CP”. Another example, it may be clearer as “The Experimental group undertook xx …times a week for xx week….” Not “ Patients underwent two…” in the method.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "12676",
"date": "27 Nov 2024",
"name": "Amine Ghram",
"role": "Author Response",
"response": "Reviewer Comment 1: The topic under investigation is interesting, but there are some fundamental problems, such as the design of intervention. Furthermore, authors should improve the format of the presentation, suggesting having an example of a published RCT paper to follow. Response: We appreciate your feedback regarding our manuscript. We recognize the necessity for a more precise intervention design and consulted well-structured randomized controlled trial (RCT) papers to enhance the format and presentation of our work. Furthermore, we meticulously revised the intervention description to ensure adherence to the standard RCT formats. Action Taken: The intervention section has been revised to adhere to a more structured format commonly used in published randomized controlled trials (RCTs). This revision encompasses a clear delineation of the study design, intervention details, and outcome measures to enhance the methodological clarity and rigor. Reviewer Comment 2: Abstract not clear because of no information about the intervention such as weeks. Response: We acknowledge your observation and have subsequently revised the abstract to incorporate specific details regarding intervention duration, thereby ensuring comprehensive information about the study's structure for readers. Action Taken: The abstract now incorporates the following information (Lines 30–32): \"The intervention consisted of a single 40-minute session of virtual reality exercise (VRE) compared to traditional exercise (TE), conducted in a controlled laboratory environment.\" This addition provided essential details regarding the intervention and enhanced the comprehensiveness of the abstract. Reviewer Comment 3: Introduction not read because method is very confusing. Response: We acknowledge the ambiguity engendered by the initial organization of the methods section. To rectify this issue, we have restructured both the Introduction and Methods sections to enhance the clarity and logical progression. Action Taken: The Introduction has been revised to ensure enhanced alignment with the study's methodology and objectives. Furthermore, the Methods section provides a comprehensive, sequential explanation of the intervention and study design, thereby minimizing potential ambiguities. Reviewer Comment 4: Method: - Ethics considerations have been already mentioned in the design, so it would be unnecessary to repeat. - Randomization should be part of design, not a separate paragraph. Response: We would like to acknowledge this recommendation. Redundant ethical considerations were eliminated, and the randomization process was integrated into the study design section to enhance the coherence of the presentation. Action Taken: The randomization protocol has been relocated to the design section (lines 175–176), and superfluous ethical considerations have been eliminated to enhance conciseness and clarity. Reviewer Comment 5: Method: Even this study has been registered, authors still need to provide information about design, such as training and outcomes, etc. Response: We acknowledge your observation and have provided supplementary information concerning the study design, encompassing training protocols and specific outcomes. Action Taken: The Methods section now delineates the training regimen, outcome measures, and data collection processes, thereby ensuring that the study design is fully transparent and adheres to RCT guidelines. Reviewer Comment 6: Methods: Figure 1 - Authors should show how many weeks of intervention as well as a brief content for both groups. Response: Thank you for your suggestion. The intervention duration was clarified, and a concise description of the intervention for both groups was provided (Figure 1). Action Taken: Figure 1 demonstrates that the intervention was implemented as a single-session trial and a concise description of the intervention protocols for both groups was provided. Reviewer Comment 7: Methods: participants - Should use “Participants” to replace “Patients”. - Actual number of participants and characteristics should be in the results. Response: We agree with the reviewer's recommendations. The term \"participants\" has been substituted for \"patients\" throughout the manuscript, and the precise number of participants, along with their demographic characteristics, has been moved to the Results section. Action Taken: The term \"patients\" has been replaced with \"participants\" throughout the manuscript, and the characteristics of participants have been incorporated into the results section (Lines 301, Table 1). Reviewer Comment 8: Methods: Intervention - This is the main problem because it’s hard to believe it will be effective for only two times training. Response: This study has several limitations. While the present investigation focused on the immediate effects of a single session, further studies are necessary to assess the long-term impact of repeated interventions. This limitation has been addressed in the Discussion section. Action Taken: This study acknowledges this limitation and suggests that future research should incorporate extended interventions to evaluate the cumulative effects of repeated VRE sessions. Reviewer Comment 9: Results: Table 1 (missing). Characteristics of participants. Response: We acknowledge your observation and have subsequently incorporated Table 1, which delineates the participants' characteristics including age, sex, and pertinent demographic data. Action Taken: Table 1 has been incorporated into the Results section, presenting the characteristics of the study participants as requested. Reviewer Comment 10: Results: Table 2 (missing). Differences between groups in all outcomes across times. Response: Table 2 presents the differences between the groups across all outcome measures and time points. Action Taken: Table 2 has been added to the Results section to show the differences in outcomes between the traditional exercise and VRE groups. Reviewer Comment 11: The discussion and conclusion have not been read because the method and results are unstructured. Response: The Methods and Results sections have been restructured to enhance the clarity and logical progression. The discussion has been aligned to provide a coherent narrative that establishes connections among the methods, results, and conclusions. Action Taken: The Methods, Results, and Discussion sections were restructured to enhance clarity, thereby improving the accessibility and logical organization of the manuscript. Reviewer Comment 12: This paper is not easy to read because of unstructured format and fluency of English. Response: The authors acknowledge concerns regarding readability and fluency. The manuscript has undergone a comprehensive revision to enhance both the structure and fluency of the English language, thereby ensuring a more lucid and professional presentation. Action Taken: The manuscript has undergone comprehensive revision to enhance clarity, grammatical accuracy, and overall fluency, thereby improving readability while maintaining scholarly rigor. Thank you for your valuable feedback. We believe that these revisions have significantly improved the clarity, structure, and scientific rigor of our manuscript. We look forward to your feedback, and hope that the revised manuscript meets your expectations."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1597
|
https://f1000research.com/articles/13-1436/v1
|
27 Nov 24
|
{
"type": "Systematic Review",
"title": "Interventions and implementation considerations for reducing pre-treatment loss to follow-up in adults with pulmonary tuberculosis: A scoping review",
"authors": [
"Mercy Mulaku",
"Eddy Johnson Owino",
"Eleanor Ochodo",
"Taryn Young",
"Eddy Johnson Owino",
"Eleanor Ochodo",
"Taryn Young"
],
"abstract": "Background Tuberculosis (TB) is a leading cause of death worldwide with over 90% of reported cases occurring in low- and middle-income countries (LMICs). Pre-treatment loss to follow-up (PTLFU) is a key contributor to TB mortality and infection transmission.\n\nObjectives We performed a scoping review to map available evidence on interventions to reduce PTLFU in adults with pulmonary TB, identify gaps in existing knowledge, and develop a conceptual framework to guide intervention implementation.\n\nMethods We searched eight electronic databases up to February 6 2024, medRxiv for pre-prints, and reference lists of included studies. Two review authors independently selected studies and extracted data using a predesigned form. We analysed data descriptively, presented findings in a narrative summary and developed a conceptual framework based on the Practical, Robust Implementation, and Sustainability Model to map the factors for effective intervention implementation.\n\nResults We reviewed 1262 records and included 17 studies. Most studies were randomized controlled trials (8/17, 47%). Intervention barriers included stigma and inadequate resources; enablers included mobile phones and TB testing and results on the same day. We identified eight interventions that reduced PTLFU: treatment support groups; mobile notifications; community health workers; integrated HIV/TB services; Xpert MTB/RIF as the initial diagnostic test; computer-aided detection with chest radiography screening; active linkage to care; and multi-component strategies.\n\nConclusion Given the variation of healthcare settings, TB programs should consider contextual factors such as user acceptability, political commitment, resources, and infrastructure before adopting an intervention. Future research should utilize qualitative study designs, be people-centred, and include social and economic factors affecting PTLFU.",
"keywords": [
"Tuberculosis",
"interventions",
"pre-treatment loss to follow-up",
"implementation",
"scoping review"
],
"content": "Introduction\n\nTuberculosis (TB) is a leading cause of morbidity and mortality worldwide. In 2021, about 10.6 million people fell ill with TB and 1.6 million people died, including 1.4 million HIV-negative people and 187,000 HIV-positive people.1 Worldwide, from 2015 to 2021, the cumulative reduction in TB incidence was 10% and in mortality was 5.9%, falling short of the goals set by the World Health Organization (WHO) End TB strategy for 2020 for a reduction in TB incidence of 20% and mortality of 35%.1,2 The COVID-19 pandemic was in part responsible for the limited progress in reaching these goals because of reduced access to essential services for TB diagnosis and treatment. Consequently, for the first time in a decade, TB deaths increased.1\n\nTimely initiation of effective TB treatment is one of the key strategies to reduce mortality and transmission of TB in the community.3–5 However, delays in the diagnosis and treatment of TB persist. Tragically, people who are diagnosed with TB may never start treatment at all, referred to as ‘pre-treatment loss to follow-up’ (PTLFU). When people who experience PTLFU return to the community, they may spread TB bacteria to others and eventually die.6,7 A systematic review including 23 studies from 14 countries, eight of which were in Africa, found a high proportion (up to 38%) of PTLFU in Africa.8\n\nFindings from quantitative and qualitative studies have identified several factors that contribute to PTLFU. Some of the challenges highlighted by these studies are misconceptions about TB and its management, stigma, lack of psychosocial support, unclear communication with patients on steps to take after testing positive for TB, dissatisfaction with clinic wait times, incomplete patient contact information, and human resource and financial constraints faced by healthcare workers (HCWs).8,9\n\nSeveral studies have pointed out various interventions to reduce loss to follow-up in different chronic conditions such as the use of patient navigators (i.e., people who help patients reach the next steps in care),10,11 community health extension workers,12 mobile phone reminders, and electronic patient tracking tools. In a systematic review (including 25 studies), Law and colleagues found that psychosocial support was key to reducing loss to follow-up in persons with drug-resistant TB.13 None of these interventions were directed at PTLFU in people with pulmonary TB. To our knowledge, a conceptual framework for the implementation of interventions for PTLFU has not been described.\n\nWe performed a scoping review to identify and map the available evidence on interventions to reduce PTLFU in adults with pulmonary TB. In addition, we summarized the effects of these interventions on PTLFU and described barriers and enablers to implementing it. From this, we developed a conceptual framework adapted from the Practical, Robust Implementation, and Sustainability model to guide the implementation of the identified interventions.14–16\n\n\nMethods\n\nWe based this scoping review on the framework proposed by Arksey and O’Malley and modified by Levac.17–19 The stages of the framework are (i) identifying the research question; (ii) identifying relevant studies; (iii) study selection; (iv) charting the data; (v) collating, summarizing, and reporting the results; and (vi) consultation with stakeholders (optional).\n\nThe overarching review question was ‘What is the available evidence on interventions that reduce PTLFU in adults with pulmonary TB?’ The specific review questions were as follows.\n\n1. What evidence exists on interventions to reduce PTLFU in adults with pulmonary TB?\n\n2. What are the effects of the interventions in reducing PTLFU in adults with pulmonary TB?\n\n3. What are the barriers and enablers to the implementation of these interventions in adults with pulmonary TB?\n\nEligibility criteria\n\nWe used the Population, Concept, Context (PCC) framework to guide our eligibility criteria and study selection according to the research question.\n\nPopulation as studies with the following participant characteristics:\n\n- Adults 18 years and older or as described by authors\n\n- Bacteriologically-confirmed pulmonary TB, i.e., a positive result on sputum smear, sputum culture, or sputum molecular WHO-recommended rapid diagnostic test (mWRD)\n\nConcept as interventions to reduce PTLFU, where PTLFU was defined as patients in a national TB care programme who received a diagnosis of TB based on at least one positive sputum smear, culture, or mWRD but did not start TB treatment. In this review, we adopted the definition stated in each study for PTLFU as opposed to a definition with a defined time frame.8,20,21 Interventions to reduce PTLFU were categorized into interventions targeted at patient, provider, and healthcare system levels.\n\nContext as all settings (rural and urban), all levels of healthcare (primary, secondary, and tertiary), and all countries where interventions had been used to reduce PTLFU in adults with pulmonary TB.\n\nTypes of studies. We included randomized and non-randomized studies and studies with mixed-method study designs that assessed quantitative data regarding interventions, barriers, and enablers. We excluded studies in children, studies primarily focused on extrapulmonary TB, editorials, and comments.\n\nIn this review, we defined a barrier and enabler as a systemic and/or experienced factor that reduces or enhances the potential effects of the intervention respectively.22\n\nWe performed a comprehensive search in the following electronic databases up to February 6, 2024: Cochrane Library (Issue 2 of 12, February 2024), MEDLINE (Ovid from 1946 to September 21, 2022), EMBASE (from 1947), Science Citation Index-Expanded (Web of Science from 1900), Global Index Medicus (from 1900), TRIP (Turning Research into Practice from 1997), SCOPUS (from 1966), and CINAHL (Cumulative Index to Nursing and Allied Health Literature; EBSCO host from 1937). We also searched medRxiv (from 2019) for pre-prints. We performed the search without date restriction and limited our search to the English language. We also reviewed reference lists of included studies to identify relevant articles. We used the following key search terms: “loss to follow-up”, “LTFU”, “policy”, “interventions”, “strategies”, “adults”, “Pulmonary tuberculosis”, and “Pulmonary TB”. Boolean terms OR, AND, and Medical subject heading (MeSH) terms were used during the search to identify relevant studies. We have provided the full search strategy for Medline (Ovid) in supplementary file 1.\n\nWe imported all records identified through database searching into EndNote X9 to remove duplicates23 and then transferred to Covidence for study selection.24 Two review authors (MM and EJO) independently screened titles and abstracts and then assessed full-text articles to come up with the final list of included studies. We resolved disagreements through discussion and, if necessary, consulted a third review author. We reported the results from the screening using the PRISMA-ScR flow diagram.25\n\nWe designed a data extraction form to collect information relevant to the objective of this review. MM and EJO independently piloted the data extraction form with four of the included studies and modified the form, accordingly, based on the pilot results before its final use. MM and EJO independently extracted data from all included studies, resolving any disagreements through discussion. We extracted the following data: author, publication year, study aim, study setting, income category according to the World Bank classification,26 TB burden categories according to the WHO classification for 2021 to 2025,27 study design, participant characteristics, intervention, findings, barriers and enablers in intervention implementation.\n\nWe presented a narrative summary detailing description of the intervention; whether the intervention was directed at factors related to patients, HCWs, or the healthcare system; the effect of the intervention on PTLFU; the settings where the interventions were used; and implementation barriers and enablers. We summarized the key findings in tables. We also pointed out research gaps and described implications for future research.\n\nWe adapted the Practical, Robust Implementation and Sustainability Model (PRISM) framework because it encompasses all stages of implementation (planning, implementation, and evaluation) therefore it is comprehensive.16,28,29 PRISM considers the intervention, external environment, implementation, and sustainability infrastructure, and recipients and how they relate to influencing the implementation process. Based on the review findings, we grouped the available interventions into three domains: patient-related, healthcare worker-related, and healthcare system-related.30 We then demonstrated associations by integrating the recipients, external environment, implementation, and sustainability infrastructure. We developed the framework through an iterative process and discussion among the review authors.31\n\nWe did not pursue a formal ethical review since we used published data that were publicly available. We published the protocol in the Open Science Framework (OSF).32 We reported the findings of the scoping review using Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR) guidance.25\n\n\nResults\n\nWe identified 1262 records through electronic database searching, and manual review of reference lists. After removing duplicates, we screened 770 titles and abstracts and excluded 740 irrelevant reports. We retrieved 29 reports for full-text review. We retrieved 29 reports for full-text review, excluded 12 based on eligibility criteria, and included 17 studies in the scoping review ( Figure 1). Details of the excluded studies are in supplementary file 2.\n\nWe describe key study characteristics in Table 1 (Extended data). Of the 17 included studies, eight (47%) were randomized controlled trials,33–40 four (24%) were before and after studies41–44; one (6%) was a community-based intervention45; one (6%) was a situation analysis46; one (6%) was a quasi-experimental study47; one (6%) was a community-based TB prevalence survey48; and one (6%) was a cost and cost-effectiveness analysis.49 One study was a multicentre study, covering four countries in Africa, South Africa, Zambia, Zimbabwe, and Tanzania.38 Considering the multicentre study, in total we had 20 study settings that took place in 8 countries: India (7/20, 35%), South Africa (6/20, 30%), Uganda (2/20, 10%), Malawi (1/20, 5%), Ethiopia (1/20, 5%), Zambia (1/20, 5%), Zimbabwe (1/20,5%), and Tanzania (1/20, 5%). Of the 20 study settings where the studies were conducted, eight (40%) were lower-middle income, seven (35%) were upper-middle income countries, and five (25%) were low-income countries. Nineteen study settings were considered high burden for TB, 20 were high burden for TB/HIV, and 14 were high burden for MDR-TB/rifampicin-resistant TB. The participants were people with TB, HCWs, healthcare managers, and community residents.\n\nWe identified eight interventions from the included studies. We summarized the interventions together with enablers and barriers in Figures 2 and 3 and provided detailed information on enablers and barriers for the interventions in the Supplementary file 3 and Supplementary file 4 respectively.\n\nFive studies evaluated interventions at the patient level.\n\nTreatment support group\n\nA situation analysis in India assessed the effect of treatment support groups (TSGs) in providing information and access to quality health services to people with TB.46 A TSG was defined as a ‘non-statutory body of socially responsible citizens and volunteers to provide social support to each needy TB patient safeguarding his dignity and confidentiality by ensuring access to information, free and quality services, and social welfare programs, empowering the patient for making decision to complete treatment successfully’. The TSG was meant to support people with TB from the time of diagnosis to the completion of treatment. The study found a decrease in the proportion of people experiencing PTLFU from 5% to 0% in the latest diagnostic cohorts. Success factors included high literacy rates in the community, strong political commitment, and human and financial resources. Challenges included lack of community advocacy for TSG services, lack of social inclusion standards, potential compromise of patient dignity and confidentiality and difficulties in holding individuals with diverse interests to the common goal of TB care.\n\nMobile health interventions\n\nThree randomized controlled trials and a community-based TB prevalence survey evaluated mobile health (m-health) interventions.33,36,37,48 Two studies were conducted in India. One study found a 50% reduction in PTLFU and a reduction in delays in TB treatment initiation using telephone voice call reminders in addition to traditional referral letters and counselling compared to a control group that only received the referral letter and counselling.36 The other study found WhatsApp messenger to be more effective than referral slips in communicating results during a community-based TB prevalence survey increasing patient registration for TB treatment from 55% to 100% and reduced the PTLFU from 45% to zero percent from the start to the end of the survey period.48\n\nThe other two studies were conducted in South Africa. One study found that using short message service (SMS) to notify patients of their results was effective in initiating TB treatment compared to no SMS notifications; the SMS group saw a significantly shorter time to treatment initiation compared to the control group.37 The other study randomized patients into three groups: 1) the control, people who did not receive any SMS reminder; 2) people who received a simple reminder to return to the clinic to collect their results; and 3) people who received a longer SMS reminding them to return to the clinic and that people die unnecessarily from TB because it can be cured. The results showed that sending an SMS the evening before the return date increased by 13% the likelihood of a patient returning to the clinic and start treatment, with the effect being larger in people living with HIV (39%).33\n\nThe studies described several enablers for the m-health interventions: patients owning mobile phones with reliable up-to-date phone numbers, and be ready to register for the interventions; affordable calls and SMS charges; simple messages that do not reveal too much about the person; and training and financial support for the HCWs to deliver the intervention. A functional communication system with language preferences is also crucial. Barriers included phone battery depletion, power issues, phone sharing, and changing phone numbers which hindered timely message delivery.33,36,37\n\nTwo studies evaluated community-based interventions at the provider level.39,45 In a randomized trial conducted in Ethiopia, 12 communities received the intervention, where health workers from health centres collected sputum samples from people with presumptive TB and brought the samples to the diagnostic centre to be examined by microscopy and 20 communities did not. The trained community promoters distributed leaflets, discussed symptoms of TB during home visits and popular gatherings and encouraged symptomatic individuals to visit the outreach team or nearby health facility. After one year of the intervention, time to treatment decreased by 55% to 60% in the intervention group compared with 3% to 20% in the control group. The weighted mean duration differences between the intervention and control groups were statistically significant.39 The second study in India evaluated a community-based active case-finding approach, where two TB reporting units received the intervention and the other two reporting units did not. The intervention comprised CHWs screening people for TB symptoms in the community, making referrals to government facilities, collecting sputum for transport to government laboratories, and supporting TB treatment. During the intervention, the number of people screened, referred, tested, provided test results, and initiated treatment were recorded and PTLFU decreased from 38% at baseline to 32%.45\n\nThe studies described the following potential enablers: training and financial support (monthly stipend, travel, and communication allowance) for CHWs; having CHWs from the same community as patients to enhance acceptability and success of the intervention; engagement and involvement of community leaders; regular home visits; health education; actively tracking referrals; availability of diagnostic facilities for referral from the community; and monthly outreach clinics. However, they pointed out that in the facilities they could only access smear microscopy which has lower sensitivity for TB than molecular tests.39,45\n\nTen studies evaluated interventions at the healthcare system level.\n\nMulti-component intervention package\n\nTwo studies utilized multicomponent strategies.41,44 The first study was conducted in India, which used a before and after design, measured the effectiveness of an intervention package that consisted of field workers who were recruited and posted at different medical colleges. The workers were responsible for offering counseling, health education and conducted follow-up visits for patients who did not attend the clinic or respond to phone calls. At the end of the 6-month intervention period, they compared number of referred people with TB initiated on treatment in peripheral health institutions and found that it improved from 46% at baseline to 66% and the difference was statistically significant. The key enablers included dedicated staff who conducted follow-up and were paid incentives for motivation. Additional enablers were training and regular supervision of health workers; having correct phone numbers and postal addresses for the follow-up visits and facilitating regular communication between the HCWs in the referral facilities. The factors that deterred the success of the intervention comprised insufficient or irregularly paid monetary incentives and incorrect or missing contact numbers for patient follow-up.41\n\nThe second study, a Ugandan study, used before and after study design to evaluate the feasibility of a multifaceted intervention to improve treatment initiation among people with TB. The intervention involved medical education sessions for HCWs to understand the magnitude and consequences of PTLFU, modified laboratory request forms to collect detailed patient contact information, redesigned clinical workflow to improve sputum testing timeliness and providing desk phones to both the laboratory and outpatient department to enhance results dissemination. The study found that the median turnaround time for sputum test results improved from 12 hours to 4 hours post-intervention. The proportion of patients starting treatment within two weeks of diagnosis and those receiving same-day diagnosis and treatment initiation improved from 59% to 89% and 7.4% to 25%, respectively.\n\nKey enablers for the intervention included proper documentation of patient contacts, analysis of samples as they come in, and availability of airtime on phones for prompt communication of test results. The study highlighted barriers such as limited staff in the laboratory and clinic areas, lack of transport for patients to come back to the facility for treatment initiation even if the results came out the same day, and limited TB treatment operating hours.44\n\nA Ugandan study evaluated the economic impact of a multicomponent strategy in a pragmatic cluster randomised trial. Participants were randomised into two groups: the intervention group, which used decentralized point of care molecular testing using the GeneXpert Edge platform, streamlined clinical work flows and performance feedback using monthly report cards, and the control group, which continued with routine care where sputum smear microscopy was performed onsite and molecular Xpert® MTB/RIF (Cepheid, Sunnyvale, CA, USA) performed at a centralised facility according to the national guidelines. The intervention strategy increased the number of patients diagnosed with TB and treated promptly, with a 10% increase in per-test cost of Xpert testing compared to routine care.\n\nThe high patient volume of about 500 people with TB annually made the strategy cost-effective. The GeneXpert system could also be used to test other diseases like COVID-19 and human papillomavirus. Having low patient volumes for TB testing were identified as a barrier.40\n\nUse of Xpert MTB/RIF as the initial diagnostic test\n\nTwo studies assessed Xpert MTB/RIF, an mWRD, as the initial diagnostic test for TB.34,42 In India, a before and after study compared the proportion of PTLFU during two time periods, one year before and one year after the introduction of Xpert MTB/RIF. In addition to Xpert MTB/RIF, the study utilized trained CHWs to identify people with TB symptoms and to help track patients. The study showed that the proportion of PTLFU decreased from 11% before the intervention to 4% after the intervention.42 A cluster-randomized trial conducted in South Africa compared the effect on time to appropriate TB treatment initiation when GeneXpert was placed in a centralized sub-district level laboratory versus the clinic as a point-of-care (POC) test. The study found that the proportion of participants with culture-positive pulmonary TB initiated on appropriate TB treatment within 30 days was 76.5% in the laboratory arm and 79.5% in the POC arm, although the difference was not statistically significant. The median time to initiation of TB treatment was 7 days in the laboratory arm and 1 day in the POC arm.34\n\nFor the strategy using Xpert MTB/RIF as the initial diagnostic test to work the following enablers were key: availability and accessibility of Xpert MTB/RIF cartridges and reagents; having results available on the same day of testing; infrastructure support (stable electricity supply, temperature control, adequate storage facilities); trained personnel and having simpler, more sensitive, and high-test volume capacity for POC diagnostics for economic feasibility. In the study where CHWs did follow-up, the following measures were in place to ensure that the Xpert MTB/RIF strategy worked: training every three months; a monthly stipend; involving CHWs from the same community as people with TB; and having the CHWs carry out monthly outreach in the villages. On the other hand, the barriers to the intervention were inadequate human and financial resources, long waiting times, and restricted operating hours.34,42\n\nTwo studies conducted an economic evaluation using Xpert MTB/RIF.38,49 The first study used data from a multi-centre trial (South Africa, Zambia, Zimbabwe, and Tanzania) to compare costs and clinical outcomes of POC Xpert MTB/RIF versus smear microscopy for diagnosing TB. The findings showed that while POC Xpert MTB/RIF might be more expensive than smear microscopy, it likely offered good value since it was associated with more people being started on treatment.38 The second study, conducted in South Africa, used data from a pragmatic parallel cluster randomized trial.50 The data were used to develop a mathematical model to explore the cost-effectiveness of the TB diagnostic algorithm. The findings suggested that the use of the algorithm in a high TB prevalence setting with a well-developed laboratory infrastructure might reduce PTLFU, although it would provide only minor reductions in mortality. However, larger benefits in health outcomes could be achieved by additional investment in the health system such as improving access to additional tests after a negative TB test.49\n\nIntegrated HIV/TB services\n\nOne before and after study conducted in India tested the efficacy of a new model for delivering integrated HIV/TB services to improve the retention of co-infected individuals. At the end of the evaluation period, there was a 60% reduction in loss to follow-up and timely initiation of TB treatment. To enable this model to work, the study reported the following factors: having a policy in place that allows for cross-referrals; training health providers; tracking patients by telephone calls and home visits; referring patients to access TB and HIV services within the same health facility; and regular monitoring of the program. The authors proposed introducing an online tracking system and processes to decrease the multiple visits required by health providers.43\n\nHospital recording and an alert and response patient management\n\nA quasi-experimental study in South Africa evaluated the impact of linkage to care interventions on PTLFU in three provinces. The study assigned hospital recording and alert and response patient management interventions to each subdistrict. In hospital recording intervention, the existing routine referral mechanisms were utilized. The data clerks at each hospital identified newly diagnosed patients with TB and shared the information with the hospital staff to confirm treatment initiation. On the other hand, the alert-and-response patient management intervention identified all TB patients at selected primary healthcare facilities in addition to those identified in hospitals using routine data. The clerks in the hospital ensured patients not started on treatment after diagnosis were followed up by SMS, phone calls, and home visits by CHWs. The patients without telephonic information were immediately linked to CHWs. The study found a relative reduction in PTLFU in two provinces (42.4% and 22.3%) and no change in one province when you compare the baseline and intervention periods. The relative reduction was greater in subdistricts where alert and response patient management were implemented (34.2% to 49.3%) compared to subdistricts where hospital-recording was implemented (13.4%to32.2%). The key enabler to this intervention is that it was affordable given that it utilised the existing resources in the health system. The study highlighted limited staff to carry out linkage activities especially during the COVID-19 pandemic as a barrier.47\n\nComputer-aided digital X-ray screening for TB with sputum Xpert MTB/RIF testing\n\nIn Malawi, a three-arm randomized trial investigated the costs and yield of systematic HIV/TB screening using computer-aided digital chest X-ray (DCXR-CAD).35 Participants were randomized to standard of care (SOC), health worker-directed HIV/TB screening; oral HIV testing and linkage to treatment (HIV screening), or oral HIV testing and linkage to treatment with additional digital chest X-ray screening for TB interpreted by computer-aided diagnosis software (CAD4TBv5 version 4.12.2 (Delft Imaging, the Netherlands) with sputum Xpert MTB/RIF testing for participants with CAD4TBv5 score above 45 (HIV/TB screening).35 Participants were followed for 56 days to establish the time to TB treatment, missed TB and HIV diagnoses, and cost-effectiveness The median time to TB treatment initiation was shorter (1 day) in the HIV/TB screening arm compared to the SOC arm (11 days) and HIV screening arm (6 days).\n\nAlthough not cost-effective at the end of eight weeks of follow-up, computer-aided TB screening improved the quality of life of people with TB symptoms. However, the intervention needs to be utilized in a setting with large-scale screening, digital X-ray machine availability, and trained personnel. On the other hand, having intermittent power supplies, limited internet availability, lack of availability of maintenance and servicing personnel, and limited laboratory capacity to handle potential increased sputum samples for confirmatory testing will be barriers for the intervention to work.35\n\nThe framework ( Figure 4) describes practical options to minimize patient losses before starting treatment and may enable decision-makers to make recommendations applicable to their settings.\n\n\nDiscussion\n\nOur scoping review identified eight interventions from 17 quantitative studies from LMICs with one study utilizing a qualitative component. Most studies were randomized controlled trials (47%) or before and after interventions (24%). The interventions focused on offering people-centred care, such as through TSGs and timely test results, as well as prompt treatment initiation by using multi-component strategies, Xpert MTB/RIF as the initial diagnostic test, integrating TB/HIV care, active linkage to care, and leveraging the CHWs network. Although studies included in this review assessed the use of Xpert MTB/RIF, we note that it has now been superseded by Xpert MTB/RIF Ultra. Our review highlighted key enablers and barriers for implementing these interventions and proposed a framework emphasizing the need to consider patient characteristics, organizational factors, external influences, and infrastructure for successful implementation and sustainability.\n\nTreatment support groups (TSGs) showed a reduction of PTLFU though this intervention was not tested in a randomized controlled trial. Patient support groups have been proposed as one of the ways of reducing TB-related stigma, a key contributor to PTLFU, and have been associated with better treatment outcomes for people with TB.51,52 Patient support groups have been suggested as one way of promoting the well-being of people with chronic illnesses apart from managing the disease. In a systematic review conducted by Thompson and colleagues,53 the effectiveness was not clear though some studies reported positive health outcomes such as improvement in quality of life and clinical outcomes. Embuldeniya and colleagues conducted a qualitative synthesis and found that the positive impact of peer support interventions depends on how ‘peers’ are defined and also addresses the hierarchical aspects of the peer support intervention.54 In this study, for the TSG to work, a high literacy rate from the community was required to facilitate capacity building of the support group; community advocacy and strong political commitment which enabled the operations of the support groups, standards for social inclusion, and human and financial resources for the sustainability of the support groups. Moreso, maintaining the dignity and confidentiality of the people with TB was considered so that mutual trust was developed in the TSG and maximum benefits were achieved. For this setting, the aforementioned factors promoted the success of the TSG although different settings need to conduct participatory action research to offer peer support interventions that reflect the local needs.\n\nMobile-health (m-health) interventions were reported in four studies.33,36,37,48 Three studies reported a shorter time from diagnosis to treatment initiation while one study reported reduction of PTLFU over a period of time. These interventions improve communication and coordination between healthcare workers and patients, addressing navigational challenges in TB care.55 Although m-health is gaining popularity and showing positive health outcomes, most research has been conducted in high and upper-middle-income countries, raising questions about its applicability in low and lower-middle-income settings.56 Studies found m-health interventions feasible due to affordable call and SMS costs. Key implementation considerations include mobile phone ownership rates, valid phone numbers, language preferences, confidentiality, staff training, minimizing phone sharing, and providing long-life batteries to ensure that users receive messages at an appropriate time.33,36,37 These factors align with findings from two systematic reviews of barriers to m-health interventions in low and middle-income settings.57,58\n\nCommunity-based interventions were reported in two studies.39,45 Both studies used CHWs to deliver the intervention, and the proportion of those who experienced PTLFU was reduced. Community-based interventions in mental health and child and adolescent health have also been found to be effective.59,60 Training of CHWs on TB and its management and offering them financial support (monthly stipend, monthly travel, and communication allowance) are enablers for effective delivery of the intervention. Recruiting CHWs from the same community as patients may enhance the acceptability and success of the intervention. Other important considerations are conducting regular home visits, providing health education that helps in understanding TB, ways of transmission and management, tracking referrals, increasing the availability of WHO-recommended rapid tests, and involving community leaders.39,45\n\nIntegration of TB/HIV services was reported to aid the timely initiation of TB treatment and thus reduce PTLFU. People with HIV are at higher risk for TB, which is a leading cause of death for them.61–63 Effective integration can decrease patient attrition by enabling quicker referrals and coordinated care. Recommended actions to enhance integration: incorporating policies that allow for cross-referrals; involving trained HCWs; tracking patients by phone calls and home visits; referring patients to TB and HIV services within the same health facility; and regularly monitoring the program.43,64 A systematic review by Legido-Quigley and colleagues found that integration of TB and HIV services benefited both providers and patients. However, the authors highlighted challenges such as the need for staff training, addressing the perceived association of TB and HIV, infrastructure improvements (such as a private space for HIV counselling and integrated records), and TB infection prevention and control.61\n\nIn comparison to smear microscopy, Xpert MTB/RIF has been shown to reduce the time to initiation of treatment of TB and may be associated with a reduction in PTLFU.34,42,65 Key implementation considerations for the use of Xpert MTB/RIF are investments by the National TB Program in improving the laboratory infrastructure by, for example, providing a stable source of electricity, temperature control, and adequate storage facilities. Additionally, when used at POC, Xpert MTB/RIF should be positioned where there is high test volume capacity and utilize trained personnel.34\n\nMany of our findings are aligned with the WHO recommendations on approaches and strategies for increasing access to rapid TB diagnostics as the initial test. In their report, the WHO emphasises person-centred care, near patient and same-day TB testing; support for patient costs (like transportation and food vouchers); dedicated staff training; improved data management systems; and integration of TB programs with other services such as HIV.66\n\nAlthough the included studies measured the effect of interventions on PTLFU statistically, the results were consistent with a reduction in the time to treatment duration with some of the interventions reducing up to one day.34,35 This implies that the TB treatment delay was averted. Treatment delay has been associated with clinical severity and ongoing TB transmission.67–69 Thus, prompt initiation of effective treatment would reduce clinical severity, continued TB transmission, drug resistance, and TB-related deaths, thereby improving the well-being and quality of life for people with TB.3–5\n\nOf note, most of the intervention studies were conducted in India (n=7) and South Africa (n=6), both high TB burden settings. However, the findings may not apply to other high TB burden settings due to different contextual factors. Only one study included a qualitative component, limiting the insights into the acceptability and feasibility of these interventions and their implementation strategies. Also, we found no available evidence on patient navigators, people who assist patients to reach the next level of care in their TB journey, or on the electronic linkage of laboratory and treatment registers, which have been suggested as ways to reduce PTLFU in some settings.11,70 Apart from m-health interventions, Xpert MTB/RIF as an initial diagnostic test, multicomponent strategies, and community-based interventions had more than one study assessing their effect on on PTLFU, the other interventions were assessed in only one study, which limited our confidence in the study findings.\n\nOur scoping review had several strengths. First, we conducted a comprehensive search in eight different databases and searched reference lists of included studies. Second, we performed double data extraction to ensure we captured all the relevant information to the review question. Third, we extracted information on key enablers and barriers to guide intervention implementation. Lastly, we reported our findings according to the PRISMA-ScR guidance.\n\nOur review also had some limitations. We included studies published in English only and thus may have missed relevant studies written in other languages. In addition, we did not assess the risk of bias in the included studies, which could have influenced the internal validity of the findings, leading to an overestimation or underestimation of the actual benefit of the intervention.71 Unlike systematic reviews, mandatory critical appraisal of included studies is not required for scoping reviews; nonetheless, we think a risk of bias assessment would have benefitted the review.72 In addition, though considered to be an optional step in the framework,17,18 we were not able to have follow-up discussions with the relevant stakeholders to get information beyond our review findings.\n\n\nConclusion\n\nOur scoping review identified eight interventions that reduced PTLFU. The interventions targeted patients, providers, and healthcare system, though most addressed healthcare system-level challenges. The interventions reduced delays between diagnosis and treatment initiation by utilizing multi-component strategies, Xpert MTB/RIF as the initial diagnostic test, integrated HIV/TB care, CHWs, and mobile notifications. Despite these interventions reducing PTLFU, there was limited evidence on the effect of support groups and integration of HIV/TB care. Important implementation considerations such as user acceptability, infrastructure, resources, policies to guide the intervention implementation, and political commitment, are crucial before adopting the interventions given that healthcare environments vary. Our review identified only one study that had a qualitative arm that could provide more insight into the acceptability and feasibility of these interventions to inform effective approaches for intervention implementation. Future research should be people-centred and address social and economic factors that may affect PTLFU.\n\n\nEthics and consent\n\nFor this review, we did not pursue a formal ethical review and consent since the data were published and publicly available. Ethical approval and consent were not required\n\n\nAuthor contributions\n\nMM, EO, and TY gave input to the scoping review protocol. MM and EJO screened the studies. MM developed the data extraction tool, and all the authors gave their input before the data extraction process commenced. MM and EJO conducted data extraction. All authors gave their input in the description and synthesis of the data. MM wrote the first draft of the manuscript and all authors contributed to the writing of the manuscript.\n\n\nORCID identifiers\n\nMercy Namuma Mulaku: 0000-0003-2480-0814\n\nEddy Johnson Owino: 0000-0001-9549-379X\n\nEleanor Ochodo: 0000-0002-7951-3030\n\nTaryn Young: 0000-0003-2406-081X",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\nOSF: Extended data for Interventions and implementation considerations for reducing pre-treatment loss to follow-up in adults with pulmonary tuberculosis: a scoping review. https://doi.org/10.17605/OSF.IO/YEKXQ.73\n\nThe project contains the following underlying data:\n\n1. PRISMA ScR checklist\n\n2. Supplementary file 1: search strategy\n\n3. Supplementary file 2: Excluded studies\n\n4. Supplementary file 3: Enablers to interventions to reduce PTLFU\n\n5. Supplementary file 4: Barriers to interventions to reduce PTLFU\n\n6. Table 1: Key characteristics of the included studies\n\nData are available under the terms of the CC0 1.0 Universal\n\n\nAcknowledgements\n\nWe thank Vittoria Lutje for developing the search strategy and undertaking the search. We thank Karen Steingart for her support in development of the study protocol, study selection and writing of the manuscript. 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PLoS Med. 2021; 18(9): e1003752. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMajella M, Thekkur P, Kumar A, et al.: Effect of mobile voice calls on treatment initiation among patients diagnosed with tuberculosis in a tertiary care hospital of Puducherry: A randomized controlled trial. J. Postgrad. Med. 2021; 67(4): 205–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMwansa-Kambafwile J, Chasela C, Levin J, et al.: Treatment initiation among tuberculosis patients: the role of short message service (SMS) technology and Ward-based outreach teams (WBOTs). BMC Public Health. 2022; 22(1): 318. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPooran A, Theron G, Zijenah L, et al.: Point of care Xpert MTB/RIF versus smear microscopy for tuberculosis diagnosis in southern African primary care clinics: a multicentre economic evaluation. Lancet Glob. Health. 2019; 7(6): e798–e807. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShargie E, Mørkve O, Lindtjørn B: Tuberculosis case-finding through a village outreach programme in a rural setting in southern Ethiopia: community randomized trial. Bull. World Health Organ. 2006; 84(2): 112–119. PubMed Abstract | Publisher Full Text\n\nThompson R, Nalugwa T, Oyuku D, et al.: Multicomponent strategy with decentralised molecular testing for tuberculosis in Uganda: a cost and cost-effectiveness analysis. Lancet Glob. Health. 2023 Feb 1; 11(2): e278–e286. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStalin P, Manikandan M, Antony V, et al.: Identifying and addressing factors contributing to pretreatment loss to follow-up of tuberculosis patients referred for treatment from medical colleges in Pondicherry: an implementation research. Indian J. Community Med. 2020; 45(1): 27–31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDas M, Pasupuleti D, Rao S, et al.: GeneXpert and Community health workers supported patient tracing for tuberculosis diagnosis in conflict-affected border areas in India. Trop. Med. Infect. Dis. 2019; 5(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nGupta A, Singh P, Goel S, et al.: Efficacy of a new model for delivering integrated TB and HIV services for people living with HIV/AIDS in Delhi -case for a paradigm shift in national HIV/TB cross-referral strategy. AIDS Care. 2014; 26(2): 137–141. PubMed Abstract | Publisher Full Text\n\nZawedde-Muyanja S, Musaazi J, Castelnuovo B, et al.: Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda. PLoS One. 2022; 17: 17. Publisher Full Text\n\nVyas A, Creswell J, Codlin A, et al.: Community-based active case-finding to reach the most vulnerable: tuberculosis in tribal areas of India. Int. J. Tuberc. Lung Dis. 2019; 23(6): 750–755. PubMed Abstract | Publisher Full Text\n\nBalakrishnan S, Manikantan J, Sreenivas A, et al.: Social inclusion: An effort to end loss-to-treatment follow-up in tuberculosis. Indian J. Tuberc. 2015; 62(4): 230–234. PubMed Abstract | Publisher Full Text\n\nMeehan S, Hesseling A, Boulle A, et al.: Reducing Initial Loss to Follow-up among people with bacteriologically confirmed tuberculosis: LINKEDin, a quasi-experimental study in South Africa. Open Forum. Infect. Dis. 2024;1; 11(1). Publisher Full Text\n\nSelvaraju S, Malaisamy M, Dolla C, et al.: Application of mobile phone technology as intervention for the management of tuberculosis patients diagnosed through community survey. Indian J. Med. Res. 2022; 155(2): 301–305. PubMed Abstract | Publisher Full Text\n\nFoster N, Cunnama L, McCarthy K, et al.: Strengthening health systems to improve the value of tuberculosis diagnostics in South Africa: A cost and cost-effectiveness analysis. PLoS One. 2021; 16(5): e0251547. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChurchyard G, Stevens W, Mametja L, et al.: Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF. Lancet Glob. Health. 2015; 3(8): e450–e457. PubMed Abstract | Publisher Full Text\n\nNuttall C, Fuady A, Nuttall H, et al.: Interventions pathways to reduce tuberculosis-related stigma: a literature review and conceptual framework. Infect. Dis. Poverty. 2022; 11(1): 101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPotty R, Kumarasamy K, Munjattu J, et al.: Tuberculosis treatment outcomes and patient support groups, southern India. Bull. World Health Organ. 2023; 101(1): 28–35A. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThompson D, Booth L, Moore D, et al.: Peer support for people with chronic conditions: a systematic review of reviews. BMC Health Serv. Res. 2022; 22(1): 427. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEmbuldeniya G, Veinot P, Bell E, et al.: The experience and impact of chronic disease peer support interventions: A qualitative synthesis. Patient Educ. Couns. 2013; 92(1): 3–12. PubMed Abstract | Publisher Full Text\n\nThomas B, Suresh C, Lavanya J, et al.: Understanding pretreatment loss to follow-up of tuberculosis patients: an explanatory qualitative study in Chennai, India. BMJ Glob. Health. 2020; 5(2): e001974. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarcolino M, Oliveira J, D’Agostino M, et al.: The Impact of mHealth interventions: systematic review of systematic reviews. JMIR Mhealth Uhealth. 2018; 6(1): e23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKruse C, Betancourt J, Ortiz S, et al.: Barriers to the use of mobile health in improving health outcomes in developing countries: systematic review. J. Med. Internet Res. 2019; 21(10): e13263. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDemsash A, Tegegne M, Walle A, et al.: Understanding barriers of receiving short message service appointment reminders across African regions: a systematic review. BMJ Health Care Inform. 2022; 29(1): e100671. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChild and adolescent health: community-based interventions: 2023. (Accessed 18 July 2023). Reference Source\n\nCastillo E, Ijadi-Maghsoodi R, Shadravan S, et al.: Community Interventions to Promote Mental Health and Social Equity. Curr. Psychiatry Rep. 2019; 21(5): 35. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLegido-Quigley H, Montgomery C, Khan P, et al.: Integrating tuberculosis and HIV services in low- and middle-income countries: a systematic review. Trop. Med. Int. Health. 2013; 18(2): 199–211. Publisher Full Text\n\nWorld Health Organization: Models of service delivery for people with TB, HIV, and comorbidities. (Accessed 18 July 2023). Reference Source\n\nWorld Health Organization: Fact sheet on tuberculosis.2023. (Accessed 26 September 2023). Reference Source\n\nWorld Health Organization: WHO Policy on Collaborative TB/HIV Activities: Guidelines for National Programmes and Other Stakeholders. Geneva: World Health Organization; 2012.\n\nHaraka F, Kakolwa M, Schumacher S, et al.: Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis. Cochrane Database Syst. Rev. 2021; 5(5): CD012972. PubMed Abstract | Publisher Full Text\n\nWHO standard: universal access to rapid tuberculosis diagnostics. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO.\n\nJi H, Xu J, Wu R, et al.: Cut-off points of treatment delay to predict poor outcomes among new pulmonary tuberculosis cases in Dalian, China: A Cohort Study. Infect. Drug Resist. 2021; 14: 5521–5530. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTedla K, Medhin G, Berhe G, et al.: Delay in treatment initiation and its association with clinical severity and infectiousness among new adult pulmonary tuberculosis patients in Tigray, northern Ethiopia. BMC Infect. Dis. 2020; 20(1): 456. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirenfeldt J, Rudolf F, Camara C, et al.: Treatment delay affects clinical severity of tuberculosis: a longitudinal cohort study. BMJ Open. 2014; 4(6): e004818. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSubbaraman R, Jhaveri T, Nathavitharana R: Closing gaps in the tuberculosis care cascade: an action-oriented research agenda. J. Clin. Tuberc. Other Mycobact. Dis. 2020; 19: 100144. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBoutron I, Page M, Higgins J, et al.: Chapter 7: Considering bias and conflicts of interest among the included studies.Higgins J, Thomas J, Chandler J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane; 2023. Reference Source\n\nMunn Z, Peters M, Stern C, et al.: Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med. Res. Methodol. 2018; 18(1): 143. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMulaku M, Owino EJ, Ochodo E, et al.: Extended data for Interventions and implementation considerations for reducing pre-treatment loss to follow-up in adults with pulmonary tuberculosis: a scoping review.2024, November 8. Publisher Full Text"
}
|
[
{
"id": "347193",
"date": "19 Dec 2024",
"name": "Vineet K Chadha",
"expertise": [
"Reviewer Expertise Tuberculosis",
"Epidemiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction\nAuthors have summarized the effects of various interventions undertaken in high TB burden settings to address PTLFU among adult Pulmonary TB patients and the barriers and enables thereof, using standard review methods. Using the synthesized evidence, they also developed a framework as a guide for reducing PTLFU. Therefore, this publication would be of great significance. It is very well written with good flow for easy understandability of health care workers and administrators at all levels.\n\nMinor comments are as under:-\nPara 1: May update the data-figures as per the latest Global TB Report There is some repetition in 1st para of ‘results”\nTreatment support Group: This evidence is from just one district of India, has to be stated accordingly.\nLikewise for other studies, the geographical level/target group in which evidence was generated has to be mentioned.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
},
{
"id": "347189",
"date": "31 Dec 2024",
"name": "Abhishek Sen",
"expertise": [
"Reviewer Expertise Tuberculosis"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of the Article The article titled \"Interventions and implementation considerations for reducing pre-treatment loss to follow-up in adults with pulmonary tuberculosis: A scoping review\" is a scoping review that addresses pre-treatment loss to follow-up in adults with pulmonary TB, a critical issue in TB management that exacerbates transmission and mortality rates. The authors aim to identify and evaluate interventions to reduce PTLFU, discuss barriers and enablers to their implementation, and propose a conceptual framework for intervention deployment.\nKey findings of the Article\nInterventions: Eight interventions were identified, including treatment support groups (TSGs), mobile notifications, integrated HIV/TB services, and the use of advanced diagnostic tools like Xpert MTB/RIF. Barriers: Issues such as stigma, inadequate resources, and infrastructural challenges hinder effective implementation. Enablers: Mobile phone access, same-day TB testing, and community health worker (CHW) involvement emerged as facilitators. The authors developed a framework based on the Practical, Robust Implementation, and Sustainability Model (PRISM) to support context-sensitive intervention implementation.\nStrengths of the Article\nThe review synthesizes evidence from multiple databases and diverse study designs, providing a holistic view of available interventions. The conceptual framework offers practical guidance for policymakers and healthcare providers in tailoring interventions to specific contexts. By identifying these factors, the article enhances the utility of interventions in real-world settings. The use of double data extraction and adherence to PRISMA-ScR guidelines strengthens the reliability of findings. The focus on low- and middle-income countries (LMICs), where TB burden is highest, ensures the article’s practical relevance to global health priorities.\nWeaknesses of the Article\nOnly one study included qualitative data, which limits understanding of patient and provider perspectives on intervention feasibility. The predominance of studies from India and South Africa may reduce the applicability of findings to other high-burden regions with different healthcare systems. Interventions like patient navigators and electronic linkages, which have shown promise in other chronic conditions, are scarcely addressed.\nI hope this gives you an idea about my understanding of the article.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
},
{
"id": "344162",
"date": "13 Jan 2025",
"name": "Hanlie Myburgh",
"expertise": [
"Reviewer Expertise Tuberculosis and HIV",
"social aspects of disease",
"implementation science",
"health systems",
"qualitative research",
"scoping reviews"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis review makes an important academic contribution by reviewing the available evidence on interventions to reduce PLTFU in adults with pulmonary TB worldwide. As the authors justify in their introduction, PLTFU is a major contributor to suboptimal TB programme performance and control efforts. The scoping review which they conducted is rigorous and they have clearly set out their aims/objectives, process/method, as well as inclusion/exclusion criteria, following specified frameworks (e.g., PCC and PRISMA-Sc). Well done on a very important and well written/presented review. I have only minor comments for consideration.\n\nResults section: the reference on page 6’s ‘description of the interventions,’ to the eight interventions identified, is not clear in Figures 2 and 3. There are many more than 8 listed in the figure rows. For clarity, I suggest adapting the figures to identify the intervention areas more clearly, as well as in the text that follows, as the intervention under provider-level is not similarly italicized as in the other two levels.\nFigure 4, pages 11 and 12: I suggest refining/expanding the description of the conceptual framework/figure to better introduce and describe the 4 avenues/boxes identified (organizational characteristics, patient characteristics, implementation and sustainability infrastructure, and external environment) that impact on intervention implementation. While this is explained well in the discussion section, it is not equally apparent when looking at the figure and the caption, or the description of the conceptual framework at the end of the results section on page 11.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1436
|
https://f1000research.com/articles/13-962/v1
|
23 Aug 24
|
{
"type": "Case Study",
"title": "Assessing the severity of thermal discomfort in a building in the course of hot and humid climate",
"authors": [
"Thomas Janvier Matongo",
"Gilbert Roméo Hubert Ngock",
"Emmanuel Yamb",
"Léopold Mba",
"Benjamin Salomon Diboma",
"Jean Gaston Tamba",
"Gilbert Roméo Hubert Ngock",
"Emmanuel Yamb",
"Léopold Mba",
"Benjamin Salomon Diboma",
"Jean Gaston Tamba"
],
"abstract": "This work is an application of experimental temperature data previously collected in a residential building in Douala, Cameroon, in order to analyze thermal discomfort. The data was collected according to three occupancy scenarios over 12 month period using thermohygrometer sensors. The temperature data are analysed in comparison with the comfortable temperature range from 24°C to 28°C. The degree hour (DH) method was used to assess the severity of thermal discomfort in a hot and humid climate. The results reveal that the open C1, closed C2 and inhabited C3 rooms corresponding to scenarios C1, C2 and C3 respectively, have 7270.6°H, 9063.9°H and 10023°H. The inhabited room C3 has the largest DH and although the room C1 has the smallest DH, the latter largely exceeded the tolerable limit value of 1250°H set by the RE2020 Environmental Regulations. Results from this work can serve in building modelling for researchers and architects to act for the alleviation of thermal discomfort in regions with hot and humid climate.",
"keywords": [
"Residential building",
"Degree hour",
"Thermal discomfort",
"hot and humid weather",
"Douala."
],
"content": "1. Introduction\n\nDouala is a coastal city located 35km from the Gulf of Guinea in Cameroon. The city is characterized by a hot and humid weather regularly crossed by light winds of 3 to 7 km/h. Demographically and according to the National Institute of Statistics (INS) in 2019, Douala has more than 3 million inhabitants. The most urbanized area of the city is 210 km2 with 70 km2, 70% of which is built according to the Douala Urban Community (CUD). The demographic boom and the rural exodus have favoured an increase in demand for housing, leading to anarchic occupation of land and non-compliance with architectural rules adapted to the climate. This situation has led to an increase in heat islands in the city.1,2 Cinder block constructions abound due to the availability of this material on the market. The first concrete houses in the region met certain provisions and criteria such as the orientation of doors and windows in relation to the prevailing wind, ventilation holes, shutters, and prefabricated screens on the upper parts of the bays. This fosters regular home ventilation even when the bays are closed. Nowadays, these criteria are largely neglected. The trend towards glass doors and windows predominates. We regretfully note that the habits of the occupants of modern houses are among the causes of discomfort since the openings are sometimes not used properly. Doors and windows remain constantly closed, which does not favour wind circulation and air renewal. Studies related to indoor air quality show that poor air renewal can cause many illnesses, such as allergies, asthma, lung infections, headaches, as well as nose, throat and eyes irritation. Furthermore, better thermal comfort can be obtained with a good design of habitats that are adapted to the climate of the city of Douala.3 In 2012, some studies on thermal comfort conditions in the city resulted in the temperature range of 24°C to 28°C and for an interval of 60% to 69% relative humidity.4,5\n\nHowever, thermal discomfort in buildings has become a major nuisance in Douala,1 especially for modern housing made from unconditioned cinder block. The intensity of this problem which has so far been little assessed is observed at different degrees in the rooms of the same building. These differences are mainly related to the behavior of the inhabitants, wind circulation, air temperature and humidity. Oluwafemi et al in 20106carried a study in houses in Bauchi in Nigeria, and showed that thermal comfort depends on the adaptation of the occupants in their residence. It has been demonstrated that despite the existence of several factors acting on the interior environment, the occupant seems to be the most impactful element. In fact, the action of the occupant on the window and the shutter modifies air renewal as well as the management of solar gain. The works of Alison and Chungyoon in 20037 demonstrated that occupants of well-ventilated rooms have a good thermal sensation.\n\nTo assess thermal comfort, certain studies have particularly used the PMV (Predicted Mean Vote) method.4,5,7 Which aims to predict the mean value of a group of occupants on a seven point thermal sensation scale.ai Her evaluation being subjective. In addition, when it is necessary to express the severity of discomfort by period, methods such as PMV, PPD (Predicted Percentage of Dissatisfied) fail to meet this objective, and this limits their usefulness in many cases.8 On the other hand, the DH method offers the possibility of assessing the severity of discomfort by temporal stages in an inhabited or uninhabited building, which justifies its choice for the purpose of this study.\n\nSeveral studies carried in recent decades have used the DH as an index for assessing discomfort. In 2010, studies revealed the influence of exterior shading systems for a substantial reduction in DH at the level of intermediate floors during cooling periods.9 In 2013, a study carried out in a well-insulated commercial building, located in a temperate climate, showed the benefit of natural night-time ventilation provided by opening the skylights as a passive cooling strategy, which contributes to a significant reduction in DH by approximately 19% for the entire building in summer.10 In 2018, studies carried in four Moroccan climatic areas revealed that the thermal comfort of occupants increases in rooms with cantilevered beams, and the DH decreases by approximately 2.1% compared to rooms without cantilevered beams.11 Nisrine et al in 2021 studied DH in a public building whose envelope consists of four facades, the ceiling and a roof.12 They showed that the number of occupants strongly affects the DH whose intensity varies in the same direction as the number of occupants. Other studies have shown the importance of the DH index in building design since it can be used to evaluate thermal comfort objectively in buildings in inhabited or uninhabited mode.8,12 The RE2020 environmental regulation in France defines two DH thresholds: A 350°H threshold below which the building is comfortable, and a 1250°H threshold above which the building shows an unacceptable discomfort. Between these two thresholds we talk about “tolerable discomfort”.13 Thus, DH studies in the South Sahelian African area should be promoted within the framework of local regulations.\n\nFrom the literature review, it appears that the level of thermal discomfort is a primary factor in assessing building performance. Also, the DH index is one of the evaluation methods often used for a specific occupancy scenario in a building. The originality of this work lies in the fact that thermal discomfort is assessed in the same building according to three simultaneous occupancy scenarios representing the real situations of a habitat. We wonder about the intensity of DH in a room depending on whether it is inhabited, closed uninhabited or open uninhabited.\n\nThe purpose of this work is to assess the intensity of thermal discomfort based on experimental data and using the DH index in a hollow agglomerate block room located in a hot and humid area, following three simultaneous scenarios with data previously collected over a12 month period.\n\nThe methodology adopted in this work begins with the construction of an experimental building of R+1 with three test rooms of the same measurements upstairs. The data acquisition system which consists of thermohygrometers and a computer is installed in the experimental premises. Three occupancy scenarios are then defined for the three test premises: the first premises is open and not occupied during the experimentation phase; the second is closed and not occupied and the third is occupied in real conditions according to the behaviour of people in the region. The collection, processing and storage of air temperature and relative humidity data from the different rooms is carried out. Moreover, the thermal discomfort index is determined by the method of the degree of discomfort hours of the premises and the thermal discomfort rate.\n\n\n2. Methods\n\nThe experiment was carried out in Douala which is a city located in the Littoral region of Cameroon, a country in central Africa. Cameroon stretches from the Gulf of Guinea to Lake Chad. It extends in length from the 2nd to 13th degree of North latitude and in width from 6th to 16th degree of East longitude. The opening to the sea and its stretch give the country a wide variety of climates.14,15 The Littoral region is positioned from the 3°57’30”N to 4°7’30”N and from the 9°37’30”E to 9°50’0”E (Figure 1). The place is an area with a hot and humid climate.5,16 Humidity in this area varies between 65% to 98% and temperatures between 19°C and 32°C with an average of 25°C.17 Douala records high rainfall due to the proximity of the city to the Atlantic Ocean, that is 175 to 200 rainy days per year, with a water depth of 4500mm.18 The most urbanized area is 210 km2 and according to INS, littoral statistical yearbook 2019, Douala had 3,049,034 inhabitants in 2018 with an average annual population growth rate estimated at 5% per year over the last 30 years.19\n\nThis figure was reproduced with permission from the autors.20\n\nThe experimental building is a modern R+1 building with cement blocks as an envelope. The building has three rooms of the same size, built upstairs. The three (03) experimental rooms have equivalent surfaces of 9.30m2. The walls are built from 15x20x40cm cinder block. The thickness of the cement mortar coating is 2cm. The interior and exterior surfaces of the walls are painted white. The floor is a 16x20x50cm hollow body floor covered with a 6cm thick screed and 0.5cm thick ceramic tiles. The roof is made of 0.5mm aluminum sheets, with a 4mm thick plywood ceiling. There are wooden doors measuring 3x80x210cm. We also have glazed windows of 0.4x80x100cm. The ceiling is 2.80m high (Figure 2). There is data acquisition equipment in the experimental rooms and in the outdoor environment.\n\nFor this purpose, three occupancy scenarios were carried out\n\n- Scenario 1 (C1): open uninhabited room with the door and windows open;\n\n- Scenario 2 (C2): closed uninhabited room with the door and window closed;\n\n- Scenario 3 (C3): inhabited room.\n\nIt is a temperature and relative humidity recorder, manufacturer by EXTECH®, RHT10 model; Copyright © 2014 FLIR Systems, Inc. These characteristics are given in Table 1 below.\n\nA laptop computer Intel® core ™ i5-4200U CPU @ 1.60GHz 2.30 GHz, is used for processing and drawings\n\nThermohygrometers are suspended from the ceiling, 1.10 m from the floor inside each of the three rooms (C1, C2 and C3), in accordance with ASHRAE standard 55. Another thermohygrometer is placed in the exterior environment to acquire the temperature and humidity of the outdoor air. The data recording interval is set at 1 hour. Temporal data is collected over a one-year period, from January 2019 to December 2019.\n\nTo assess discomfort, we used the hour degree method. Then, we calculated the discomfort rate.\n\n2.6.1. DH (Degree of summer discomfort time)\n\nThe DH is the sum of the positive differences between the interior temperature and the constant threshold temperature common to all building uses. It is determined over a one-year period and expresses the duration and intensity of periods of discomfort in the building.9–11,21–25 His makes it possible to calculate the sum of discomfort intensities per year in a room,26,27 hour by hour see equation 1.23,25,28\n\nTi = Resulting interior temperature.\n\nTs = Comfort threshold air temperature and has a value of 28°C.4,5\n\nDH = Degree hour.\n\nN = Total number of hours over a year which is 8760.\n\nAccording to the RE2020 environmental regulation, there are two thresholds for DH.8,27\n\n• 1 low threshold of 350°H => Comfortable building\n\n• Between 350°H and 1250°H => Discomfort is tolerable\n\n• 1 high threshold of 1250°H => Uncomfortable building\n\n2.6.2. Summer discomfort rate\n\nTo determine the proportion of annual hours of discomfort in each room, we calculated the discomfort rate (equation 2).11\n\n\n3. Results and Discussions\n\nData collected outside and in the experimental premises are analyzed, and the thermal comfort in the premises is assessed by season and over the entire year.\n\nAs in other previous studies, the monthly average temperature and humidity data in Table 2 show that Douala has a hot and humid climate.17–18,20 February is the hottest month with an average temperature of 30.8°C ±2°C, while August is the coldest with an average temperature of 26.4°C ±2°C The average humidity varies between 75% and 87.7% ±8%.29\n\nThe temperature data are analysed in comparison with the comfortable temperature range from 24°C to 28°C\n\n3.2.1. Analysis during the hot season\n\n\n\na) The hottest day\n\nFigure 3 below shows the TC1, TC2, TC3 and TExt graphs of the hottest day in February over 24 hours.\n\nThe maximum outdoor temperature was reached on February 10 at 3 p.m. with 40.93°C (RH=43.8%).\n\nLooking at Figure 3, we see that this day was particularly marked by high temperatures above the upper threshold temperature for thermal comfort in the three occupancy scenarios.\n\nFor the open room C1, the heat peak was reached at 4 p.m. with 32.93°C, while the peak was observed at 6 p.m. in the closed room C2 with 32°C. Finally, the peak is reached at 5 p.m. in the occupied room C3 with 32.27°C.\n\nThe curves of rooms C2 and C3 are almost identical over certain time intervals. This can be explained by the absence of the occupant in the room at these times.\n\nb) The hottest month\n\nFigure 4 below shows the TC1, TC2, TC3 and TEx graphs over 28 days for the month of February.\n\nOutdoor temperatures (TEx) vary from 25 to 41°C, the peak of outdoor temperatures is generally reached at 3 p.m. The temperature peak in rooms C2 and C3 is observed around 6 p.m., i.e. a peak phase shift of 3 hours compared to the outside. This can be explained by the inertia of the building envelope. We see that the temperature curves TC2 and TC3 of scenarios C2 and C3 are above the maximum threshold temperature (T high) from February 1 to 25. For scenario C1, we observe small, comfortable periods of 2 to 3 hours early in the morning.\n\n3.2.2. Analysis during the cold season\n\na) The coldest day\n\nFigure 5 below shows the TC1, TC2, TC3 and TEx graphs over 24 hours of the coldest day of the month of August.\n\nThe minimum outdoor temperature was obtained on August 29 at 4 p.m. with 32.04°C (Rh = 69.6%).\n\nFigure 5 shows the temperature progress in the rooms and outside compared to the hot comfort threshold. It is noted that the heat peak was reached at 6 p.m. for the three occupancy scenarios with 29.17°C for C1, 28.08°C for C2 and 28.61°C for C3.\n\nIt is a particularly comfortable day in the three rooms with a period of discomfort ranging from 3 p.m. to 9 p.m. for room C1, from 4 p.m. to 10 p.m. for room C2 and from 6 p.m. to 9 p.m. for room C3.\n\nb) The coldest month\n\nFigure 6 below shows the TC1, TC2, TC3 and TEx graphs over 31 days for the month of August.\n\nOutdoor temperatures (TEx) vary from 23°C to 32°C, the peak of outdoor temperatures is generally reached at 3 p.m. The temperature peak in rooms C2 and C3 is observed around 6 p.m. We see that the temperature curves TC2 and TC3 remain between the two high and low thresholds from August 1 to 28. For scenario C1, we observe periods of exceeding the lower limit of thermal comfort of 2 to 7 hours during the first 10 days of the month. This can be explained by the light rains that fall daily during this period.\n\n3.2.3 Analysis during the entire year\n\nFigure 7 below shows the TC1, TC2, TC3 and TEx graphs over the 365 days of 2019.\n\nThermal discomfort is noted in closed rooms C2 and inhabited rooms C3 on one hand, extending over a large number of days, except between the 200th and 260th day of the year when acceptable thermal comfort can be observed. On the other hand, in the uninhabited open room, a long period of acceptable comfort is observed between the 179th and 325th day. These periods of acceptable thermal comfort correspond to the main rainy season.\n\nThe degrees of discomfort hours and the thermal discomfort rate in the test rooms for the three scenarios are shown in the figures below over the year.\n\n3.3.1. The number Degree hours of thermal discomfort\n\nFigure 8 below shows the number of summer discomfort hours per month for scenarios C1, C2 and C3\n\nWe notice a peak in hours of discomfort in the month of December for scenarios C2 and C3 with respectively 739 hours and 724 hours, on one hand. ON the other hand, for scenario C1 the peak is reached in February with 536 hours this can be explained by the drop humidity in February. Furthermore, there was a considerable drop in the number of hours of discomfort in July and August. This period corresponds to the rainy season with fine drops falling throughout the day making the air humidity very high. The greatest number of hours of discomfort occurs in December in rooms C2 and C3. This may be due to fog despite the high temperatures.\n\n3.3.2. Degree hour of thermal discomfort\n\na) Degree hour of monthly summer discomfort\n\nFigure 9 shows the degree hours of monthly discomfort for scenarios C1, C2 and C3.\n\nA decrease in the DH is observed during the rainy season which extends from July to October as well as a period of tolerable discomfort in July and August with less than 100°H/month.\n\nb) The Degree hour of the annual discomfort\n\nFigure 10 shows the degree hours of annual discomfort for the occupancy scenarios. Room C3 has the highest discomfort degree hour with 10023°H, followed by room C2 with 9063.9°H, while room C1 has 7270.6°H. This corroborates the results of other research works such as that of Nisrine Laghmich et al. in 202115 according to which the DH increases in the same direction as the number of occupants. Results also reveal that the renewal of air linked to the opening of the bays leads to an annual reduction in DH.\n\n3.3.3. The Degree hours of summer thermal discomfort of the three scenarios compared to RE2020\n\nCompared to RE2020 which sets the maximum DH at 1250°H,17 Figure 11 above shows that:\n\nThe DH is 5.8 times higher in room C1, 7.2 times higher in room C2 and 8 times higher in room C3. We notice that the discomfort in a premises made of concrete blocks in a hot humid climate is far above the tolerable limit value provided for by RE2020. Although these are unlivable conditions in other countries, the inhabitants of the city of Douala seem to adapt well.4\n\nTable 3 below gives the percentage of annual hours where the temperature is above 28°C.\n\nTable 3 shows that:\n\n• The discomfort rate in the closed and uninhabited room C2 is relatively low compared to the inhabited room C3. This can be explained by human presence which is a source of heat.30\n\n• For the open room C1, the discomfort rate decreases by 19.8% compared to the closed room. This can be explained by the opening of the windows which promote permanent ventilation of the room. Other studies in temperate climates have shown that natural night time ventilation provided by the opening of skylights contributes to a 19% reduction in DH in summer discomfort.31\n\n\n4. Conclusion\n\nThis work allowed to assess the severity of summer discomfort in a residential building made of cinder block in the city of Douala, in Cameroon. We have set to study the variation in the degree of discomfort time following different scenarios in three rooms of the same measurements. Scenario 1 (C1) with an open uninhabited room with the doors and windows open, Scenario 2 (C2) with a closed uninhabited room with doors and windows closed, and Scenario 3 (C3) with an inhabited room. The results obtained show that the DH in a room with a hollow agglomerate block envelope in a hot and humid climate exceeds more than five times the tolerable limit of 1250°H set by RE2020. Opening doors and windows allows a reduction in DH of 19.8% compared to a closed room. Occupants have a strong impact on the increase in DH due to the fact that they are a source of heat and also due to their action on the bays. Nevertheless, opening doors and windows does not seem to be enough to make the building comfortable. The observation made in this work can be remedied by solutions that are applicable to buildings in this type of climate. Namely, a better choice of construction site, good orientation of the building and openings, good organization of spaces, good protection of the building against solar rays, good natural ventilation and a reasonable choice of construction materials. For that purpose, this study proves to be useful to designers and real estate developers in order to make an optimal choice with regard to the building envelope, its protection against solar radiation and natural ventilation. It can also be important that room occupants take action to renew the air and reduce solar radiation. Eventually, the study can help public authorities improve regulations in the real estate sector in hot and humid climates.",
"appendix": "Data availability statement\n\nThe data used in this work are available online in a Data Article: Experimental data showing the thermal behaviour of a residential building in a hot and humid climate on three scenarios: An empty room with a closed door, an empty room with an open door, and a normal inhabited room, doi: https://doi.org/10.1016/j.dib.2022.107906. 29\n\nThat data article contains the following underlying data under the terms of the CC BY license (http://creativecommons.org/licenses/by/4.0)\n\n1- tables of raw data collected in the study area over a 12-month period\n\n2- figures (photos and curves)\n\n\nReferences\n\nAwuh ME, Ikekpeazu FO: Assessment of Urban Heat Island (Uhi) Situation in Douala Metropolis, Cameroon. Journal of Geography and Earth Sciences. June 2014; 2(1): 55–77. ISSN: 2334-2447 (Print), 2334-2455 (Online).\n\nOmonijo AG: Assessing seasonal variations in urban thermal comfort and potential health risks using Physiologically Equivalent Temperature: A case of Ibadan, Nigeria, Urban Climate.2017. Publisher Full Text\n\nKemajou A, Mba L: Matériaux de construction et confort thermique en zone chaude: Application au cas des régions climatiques camerounaises. Rev. Energ. Renouv. 2011; Vol. 14(2): 239 – 248. Publisher Full Text\n\nKemajou A, Mba L: Le confort thermique en climat tropical humide vers un réaménagement des normes ergonomiques. Rev. Energ. Renouv. 2012; Vol. 15(3): 427 – 438. Publisher Full Text\n\nMba L, Meukam P, Kemajou A: Application of artificial neural network for predicting hourly indoor air temperature and relative humidity in modern building in humid region. Energ. Buildings. 2016; 121: 32–42. Publisher Full Text\n\nOluwafemi K, Akande AM: Indoor thermal comfort for residential buildings in hot–dry climate of Nigeria. Energy Use Build; 2010.\n\nKwok AG, Chungyoon C: Thermal comfort in Japanese schools. Sol. Energy. 2003; 74: 245–252. Publisher Full Text\n\nShide S, Esteban E, Guillén HS: Exceedance Degree-Hours: A new method for assessing long-term thermal conditions. John Wiley & Sons Ltd; 2021; 2021. . Publisher Full Text\n\nHélder SA: Thermal comfort analysis of buildings using theoretical and Adaptive models. Lisbon: 2010. October 2010. Thèse.\n\nLapisa R, Bozonnet E, Abadie MO, et al.: Cool roof and ventilation efficiency as passive cooling strategies for commercial low-rise buildings – ground thermal inertia impact. Adv. Build. Energy Res. 2013; 7: 192–208. Publisher Full Text\n\nHaitham S, Ahmed M, Mustapha K, et al.: Shading devices optimization to enhance thermal comfort and energy performance of a residential building in Morocco. Journal of Building Engineering. 2018; 18: 292–302. Publisher Full Text\n\nNisrine L, Zaid R, Lapisa R, et al.: Numerical analysis of horizontal temperature distribution in large buildings by thermo-aeraulic zonal approach. Build. Simul. 2021; 15: 99–115. Publisher Full Text\n\n[Accessed 15 may 2022]. Reference Source\n\nde Monza J-P : Cameroun. IUCN, L’Atlas pour la conservation des forêts tropicales d’Afrique. Ed, Paris.1992; 1992: 143–150.\n\n[Accessed 6/2/2022]. Reference Source\n\nMélingui A, Gwanfogbe M, Nguoghia J, et al.: Nouvelle Géographie du Cameroun 3ème. EDICEF; 1987; vol. 1987. : 120.\n\nReference des données météo. [Accessed 6/2/2022]. Reference Source\n\nYahmen DB: Cameroun. Les éditions J.A., coll Atlas de l’Afrique, Paris, 2006.2006.\n\nhttp\n\nTomen TW, Diboma BS, Bot BV, et al.: Physical and Combustion properties investigation of hybrid briquettes from tropical Sawdust: Case study of Iroko (Milicia excelsa) and Padouk (Pterocarpus soyauxii). Energy Rep. 2023; 9(2023): 3177–3191. Publisher Full Text\n\nSaid SAM: Degree-day base temperature for resident in Saudia Arabia. ASHRAE Trans. Res. 1992; 98(1): 346–353.\n\nBarroso-krause C, Adnot: Test de la méthode du tableau de bord dans le contexte d’une ville tropicale, rapport intermédiaire. Convention ADEME n°4.09.0084, CENERG, Paris, 1995.1995.\n\nJGJ134: Residential Building Energy Efficiency Design Standard for Hot Summer/Cold Winter Region. Beijing, China: China Architectural Engineering Industrial Publishing Press; 2010; 2010.\n\nZhu Y, Cheng W, Xiaofeng G: Smart utilization of solar energy with Optic-Variable Wall (OVW) for thermal comfort.2019. Publisher Full Text Reference Source\n\nLin Y, Zhou S, Yang W, et al.: Development of Building Thermal Load and Discomfort Degree Hour Prediction Models Using Data Mining Approache. Energies. 2018; 11(11): 1570. Publisher Full Text Reference Source\n\n[Accessed 14/4/2022]. Reference Source\n\nLisanne H, Henk S: The impact of convective vapour transport on the hygrothermal risk of the internal insulation of post-war lightweight prefab housing. Energ. Buildings. 2019; 204(2019): 109418.\n\nLi J, Zhang Y, Zhu Z, et al.: Thermal comfort in a building with Trombe wall integrated with phase change materials in hot summer and cold winter region without air conditioning. Energy and Built Environment. July 29, 2022; 5: 58–69. Publisher Full Text\n\nMatongo TJ, Tamba JG, Mba L, et al.: Experimental data showing the thermal behaviour of a residential building in a hot and humid climate on three scenarios: An empty room with a closed door, an empty room with an open door, and a normal inhabited room. Data in Brief, 2022. [Dataset]. 2022. Publisher Full Text\n\nINSQ: Mesures d’adaptation à la chaleur, confort thermique et qualité de l’air intérieur dans l’habitation. Published on the website of the Institut national de santé publique du Québec; 2019. [Accessed 21/2/2019]. Reference Source\n\nLapisa R, Abadie M, Bozonnet E, et al.: Numerical analysis of thermal stratification modelling effect on comfort for the case of a commercial low-rise building. the 13th International Conference on Indoor Air Quality and Climate, Hongkong, 2014. 2014."
}
|
[
{
"id": "321441",
"date": "23 Sep 2024",
"name": "Khalid El Harrouni",
"expertise": [
"Reviewer Expertise Full professor",
"UNESCO Chair \"Education and Research in Sustainable and Bioclimatic Urban Planning and Architecture\"",
"Civil Engineering",
"Building Energy Efficiency"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper uses experimental data to assess and quantify thermal discomfort in residential buildings in a hot and humid environment. Its reliance on the DH method provides a clear metric for thermal discomfort, and its focus on real-world applications makes it relevant for architects, engineers, and policymakers. It presents a well-structured study that moves logically from data collection to analysis and recommendations.\nThe DH method is appropriate for assessing thermal discomfort, and the long-term data collection period (12 months) adds credibility to the findings. However, a brief explanation of the method might help readers unfamiliar with the concept.\nThe paper provides significant insights into the thermal discomfort challenges of buildings in hot and humid climates, and its recommendations will be valuable for improving building design in such regions. Expanding on modern technologies and policy implications could further strengthen its impact: : although the paper provides practical recommendations, it could benefit from more detailed exploration of modern cooling technologies or innovations in building materials that could further alleviate discomfort.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Yes",
"responses": []
},
{
"id": "321444",
"date": "24 Sep 2024",
"name": "Klodjan Xhexhi",
"expertise": [
"Reviewer Expertise Bioclimatic Architecture",
"Building Materials",
"Architecture Technology",
"Building Energy Efficiency"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral Comments Relevance and Contribution: The study addresses an important issue related to thermal discomfort in residential buildings in hot and humid climates, with a focus on the city of Douala, Cameroon. The use of the Degree Hour (DH) method is appropriate and relevant for quantifying thermal discomfort. This provides valuable information for architects and policymakers. Clarity and Structure: The paper is well-structured, moving logically from introduction to methods, results, and recommendations. The background and rationale for the study are adequately explained, and the methodology is presented in sufficient detail. Strengths The long-term data collection over 12 months enhances the reliability of the findings. The use of three distinct occupancy scenarios (open, closed, and inhabited rooms) provides a comprehensive analysis of different real-world conditions. Methodological Approach: The DH method is effectively used to quantify thermal discomfort, and the study provides a clear metric for assessing discomfort in residential buildings. Recommendations and Practical Implications: The paper offers practical recommendations for building design in hot and humid climates. These include considerations for natural ventilation, building orientation, and material choices. Weaknesses The method adopted for DH is adequate, though perhaps not widely known by all readers. Further explanation is needed, or at least a short description of the formula and how it is applied in this work. How about DH norms in your country? (If they do exist). It would be further elaboration to understand how the analysis of the different parameters involved, such as humidity and occupants' behavior, influences DH values in each scenario. How the modern technologies of cooling or new building materials can offer further relief from thermal discomfort. Statistical Analysis: In the context of this paper, which focuses on DH values, there are no statistical tests about the significance of the differences among scenarios. Having this would increase the weight of the conclusions. Literature Review The literature review is adequate but would benefit from the addition of more recent works on thermal comfort and building design in similar climates-particularly those offering novel solutions. Conclusion and Implications: The conclusions are generally supported by the results, but they could be more specific with policy implications and recommendations for further research. Recommendations for Improvement -A brief non-technical description of DH method will be useful to readers who are unfamiliar with the metric. -All statistical tests shall be performed to see significance of differences between various scenarios. -Widen literature review by including more recent studies and references, especially dealing with advanced building technologies and materials. -Elaborate on specific policy recommendations as well as practical applications for architects and builders. -Please do not use the word “we observe” (for instance) instead of “It is observed that”. This is valid for the entire text.\nAlthough these facts are a good starting point for understanding thermal discomfort in residential buildings within hot and humid climates, a more developed analysis and a broader context would strengthen the article.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-962
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https://f1000research.com/articles/13-1249/v1
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18 Oct 24
|
{
"type": "Research Article",
"title": "Can indoor plants reduce formaldehyde levels in the anatomy dissection hall? A study to evaluate the practicality of using plants in reducing formaldehyde levels",
"authors": [
"Adish G Joshi",
"Dhiren Punja",
"Rohini Punja",
"Adish G Joshi",
"Dhiren Punja"
],
"abstract": "Background Formaldehyde a commonly used embalming fluid for the preservation of cadavers, produces numerous short and long-term side effects on the students and staff working with it. Indoor plants have been shown to reduce atmospheric formaldehyde levels. The purpose of the study was to compare the efficacy of indoor plants in reducing formaldehyde levels in ambient air to levels deemed safe by WHO standards\n\nMethods The study was conducted in the storage room of the Anatomical dissection hall. 7 potted plants of one variety were kept in the storage room for 14 days and the Formaldehyde reading was measured using a VOC (Volatile Organic Compound) monitor. Then the same was done with no plant. This cycle was repeated 2 more times, with two different plant species. The three spieces of plants used for this study were as follows: Dracaena trifasciata, Epipremnum aureum, Spathiphyllum.\n\nResults The results were analysed and compared and it was determined that the effect of having a plant present versus having no plant present on the Formaldehyde concentration in the air was inconclusive as Dracaena trifasciata failed to reject the null hypothesis altogether (p-value>0.05), while Epipremnum aureum and Spathiphyllum rejected the null hypothesis (p-value<0.05), however they both had a weak positive correlation with formaldehyde concentration.\n\nConclusion The efficacy of indoor plants in reducing formaldehyde levels in ambient air needs to be further explored and validated since all the prior studies conducted were in controlled environment and should be done in a real time scenario for its practical and beneficial uses.",
"keywords": [
"Air quality",
"anatomical dissection hall",
"indoor plants",
"indoor air",
"volatile organic compound",
"workspace environment",
"cadaver",
"formaldehyde"
],
"content": "Introduction\n\nFormalin is an ideal embalming fluid used in the preservation of the human body since it acts as a biocide by coagulating the bacterial protoplasm and is a powerful germicide. It preserves tissues by making new complex molecules that are unfit for the growth of microorganisms.\n\nMedical students who are exposed to formaldehyde (FA) during their dissection course (Shiraishi 2006) have reported various physical symptoms, such as burning eyes, lacrimation, irritation of airways, and dermatitis. FA has attracted attention as a health hazard for students and instructors, as FA concentrations in the air of gross anatomy laboratories often exceed permissible limits. On an average, students and instructors are exposed to 5.59 ppm FA, for which the maximum permissible exposure limit, according to OSHA PEL guidelines, is 0.75 ppm—essentially more than 7 times the maximum amount—and is more than 69 times greater than the recommended levels of FA exposure in the short-term and long-term (0.08 ppm) according to the Indoor Air Quality Guidelines set by the WHO (Zuber et al. 2022; CDC n.d.; Nielsen et al. 2017). Long-term FA exposure in indoor air has been found to be carcinogenic, potentially leading to nasopharyngeal carcinoma and leukemia (Shiraishi 2006; Zuber et al. 2022; CDC n.d.; Nielsen et al. 2017). High-quality indoor air cleaners can be utilized to reduce FA levels in the air with various types of air cleaners, such as activated carbon, negative ion and photocatalytic cleaners; however, these cleaners consume vast amount of electrical power (between 39.1 W and 79.2 W), can cause secondary FA pollution, are very expensive (between $147 and $721), and are inadequate for reducing FA concentrations to meet WHO guidelines. This makes them ineffective to use in an anatomy dissection hall (Chen et al. 2007). Students and faculty utilize N95 masks as a precautionary method against the COVID-19 pandemic and wear them even in the anatomy dissection hall; however, N95 masks seem to be ineffectual at reducing FA levels to WHO standards, and hence, they fail to provide any additional benefit against the effects of FA (Chan et al. 2016). Plants affect the levels of volatile organic compounds (VOCs) in indoor environments; thus, they represent a potentially cheaper, non-electricity-consuming and greener solution for improving indoor air quality (Shaham et al. 2003). Studies of plants that reduce indoor pollution have recommended that 15 to 18 plants in 6 to 8-inch-diameter containers are required to clean the air in an average of 1,800 square foot houses. There is approximately one plant per 100 square feet of floor space (Dela Cruz et al. 2014). Studies have indicated that the average FA absorption rate of certain plants is 674 micrograms per hour for Spathiphyllum (peace lily) and 1304 micrograms per hour for Dracaena trifasciata/Sansevieria (variegated snake plant) (Wolverton and Wolverton 1993). The FA concentration in the atmosphere is affected by and directly proportional to the temperature and humidity of the air, the correlation coefficient between temperature and emission factors is greater than 0.83, and the correlation coefficient between relative humidity and emission factors is greater than 0.98 (Parthasarathy et al. 2011).\n\nPrevious studies have mentioned the usage of potted ornamental plants in the reduction of FA pollution in indoor settings, and the deleterious effects of FA on individuals, especially medical students and teaching faculty in the anatomy dissection hall, no study thus far has dealt with uniting the two, by utilizing a cheap, effective and green way of reducing FA concentration in the anatomy dissection hall.\n\n\nMethods\n\nThe protocol was approved by the Institutional Ethics Committee (IEC 343/2022) Kasturba Medical College and Kasturba Hospitals, Manipal on July 14, 2022. Though the study did not involve cadavers directly, however the specimen storage room was utilized and written informed consent was given by the body donors for teaching and research when they were alive.\n\nThe study was conducted in the cadaveric specimen storage room in the Anatomy Department, Kasturba Medical College, Manipal. The traffic into the storage room was restricted during the study period to minimize errors in recording FA levels. The storage room of the anatomy dissection hall has an area of 700 sq feet with two open windows, which were kept closed at all times, and two exhaust fans, which were not switched on during the study period. The VOC monitor installed in this room was initially used to assess the basal levels of FA fumes in the room. The values were recorded twice daily (at 9:00am and 4:00pm) for two weeks. Following which, 7 potted plants all of a particular plant species were kept in the room. Hence, there was one potted plant for every 100 sq. feet. The three species of plants used for this study were Dracaena trifasciata/Sansevieria (snake plant), Epipremnum aureum (golden pothos), Spathiphyllum (peace lily). The plants were in uniform pots with a frustum shape, with a top circumference of 79 cm and a bottom diameter of 44 cm. The height of the pot was 25 cm. The pots were kept equidistant from each other at a distance of 25 cm. However, the dimensions of the plants per se were variable. All the potted plants were placed around the cadaveric specimen storage room as seen in Figure 1. The plants were kept here for 2 weeks and the FA values were recorded twice daily. These potted plants received natural indirect sunlight for ten hours. This study was conducted during the summer season, and the temperature and humidity were noted along with the FA levels. The plants were subsequently removed, and a two-week interval was established before the plants of the next species were transferred to allow the FA concentrations to once again reach basal levels. The daily temperature and humidity were also noted.\n\nThe readings documented were tabulated, and the statistical analysis was done using IBM SPSS Statistics for Windows Version 20.0 (USA). The P value for each of the plant species was calculated separately to determine whether any of the plants had a statistically significant effect on the FA concentration in the storage room. The P value ranges from 0 to 1, where a value closer to 0 means that there is a good chance of statistical significance, while a value closer to 1 indicates a null hypothesis; i.e., there is no statistical significance.\n\n\nResults\n\nOn observing Figure 2, plotted with the plants across the x-axis and concentration of FA across the y-axis and values from Table 1, the following inference could be made regarding the FA concentration measured in the storage room:\n\n1. When Dracaena trifasciata is present, the concentration in the room was 0.03 ppm less than when there is an absence of the plant.\n\n2. When Epipremnum aureum was present, the concentration in the room was 0.01 ppm greater than that when no Epipremnum aureum was present.\n\n3. When Spathiphyllum is present, the room has 0.03 ppm more than when no Spathiphyllum is present.\n\nHence, according to the results obtained, Dracaena trifasciata had the greatest negative effect on FA levels and helped to reduce FA concentration, while Epipremnum aureum and Spathiphyllum had a comparatively different effect in its efficacy of reducing FA levels.\n\nThe P value for Dracaena trifasciata was 0.06, that for Epipremnum aureum was 0.02, and that for Spathiphyllum was <0.01.\n\nThe regressions of Epipremnum aureum and Spathiphyllum were calculated, and both had nonsignificant increase in formaldehyde levels in the air compared with the absence of plants in the storage room.\n\nHence, Dracaena trifasciata fails to reject/invalidate the null hypothesis, while Epipremnum aureum and Spathiphyllum reject/invalidate the null hypothesis but have a slight positive effect on the FA level, there was an increase in the FA levels in the storage room, which is contrary to what we were trying to establish.\n\n\nDiscussion\n\nEarlier studies conducted by multiple authors such as Teiri et al. (2018), Dela Cruz et al. (2014), Kim et al. (2008) and Wolverton and Wolverton (1993) have shown that potted ornamental plants seem to have a significant negative correlation with the FA levels. Spathiphyllum and Dracaena trifasciata in question have been shown to reduce FA significantly (Wolverton and Wolverton 1993); however, these same results were not reciprocated in this particular study. We did find a decrease in FA levels when Dracaena trifasciata was kept in the storage room; however, this change was not the same for the other 2 species of plants. While the efficacy of the Epipremnum aureum has not been particularly accurately described or reviewed in the literature, it is expected to reduce FA as well. All 3 plants failed to bring the average FA concentration in the storage room to levels deemed safe by WHO standards. However, the average FA levels in the storage room, whether there were any of the 3 plants or no plants at all, satisfied the OSHA standards. A similar result was also observed in previous studies (Gahukar et al. 2014).\n\nTemperature and humidity have a positive correlation with FA concentration, as observed in earlier literature (Parthasarathy et al. 2011), which indicates a similar positive correlation. The efficacy of the indoor plants Spathiphyllum, Dracaena trifasciata and Epipremnum aureum in reducing FA levels in ambient air contradicts the findings of earlier studies and can be explained on the basis of the following hypothesis. In previous studies (Teiri et al. 2018; Dela Cruz et al. 2014; Kim et al. 2008; Wolverton and Wolverton 1993), a constant amount of FA was pumped into a chamber; however, in the present study the FA present in the storage room in the anatomy dissection hall was evaluated and we wanted to determine the true efficacy of using potted plants in a real-time scenario. Humidity and temperature are clearly positively correlated with FA concentration, both in this study and in earlier studies (Parthasarathy et al. 2011). However, the effects of these compounds on plant FA absorption and metabolism have not been determined. Previous studies (Dela Cruz et al. 2014) have indicated the use of 1 plant per 100 sq. feet, which is the rationale behind putting 7 plants in the 700 sq. feet storage room, the conditions in the earlier study (controlled environment with known, constant quantities of FA) and this particular study (a real-time environment) differed, and a greater number of plants could impact the results of the study in a radically different way.\n\nStudies conducted for longer duration could yield different results, as potted ornamental plants become sensitized to FA and hence metabolize and remove more FA over time if they are constantly exposed to it (Wolverton and Wolverton 1993).\n\nConsidering the ill effects which long term exposure to FA could lead to as an occupational hazard (Onyeka et al. 2018); causing decreased pulmonary functions in faculty and medical students exposed to FA during anatomy dissection (Homwutthiwong and Ongwandee 2017) we hope to bring about a change in the working environment naturally. We plan to continue this study bearing the confounding factors in mind, scaling up the number of potted plants and hope that we could get an ideal environment where FA concentrations would not affect our health and learning would continue as usual. Researchers can explore the potential beneficial effects of indoor plants on reducing atmospheric pollutants, namely, FA, by such cost-effective methods. By delving deeper into this field and obtaining an ideal number and variety of plants for economically improving the air quality, especially in places with maximum exposure to FA, we hope to bring a positive change to those exposed to FA.\n\n\nConclusion\n\nThe efficacy of using indoor plants for reducing FA levels needs to be further explored since studies conducted in ambient air are rare, unlike prior studies conducted in controlled environments. This study provides a scope for improvement in the future where potted plants are kept for longer durations to study their long-term effects on FA concentrations in air and increase the number of potted plants utilized.\n\n\nEthics and consent statement\n\nThe protocol was approved by the Institutional Ethics Committee (IEC 343/2022) Kasturba Medical College and Kasturba Hospitals, Manipal on July 14, 2022. Though the study did not involve cadavers directly, however the specimen storage room was utilized and written informed consent was given by the body donors for teaching and research when they were alive.",
"appendix": "Data availability\n\nFig share: Can indoor plants reduce formaldehyde levels in the anatomy dissection hall? A study to evaluate the practicality of using plants in reducing formaldehyde levels. https://doi.org/10.6084/m9.figshare.25911100.v3 (Joshi et al. 2024)\n\nThis project contains the following underlying data:\n\n- EX sheet – Master Sheet.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: STROBE checklist ‘Can indoor plants reduce formaldehyde levels in the anatomy dissection hall? A study to evaluate the practicality of using plants in reducing formaldehyde levels. https://doi.org/10.6084/m9.figshare.25911100.v3 (Joshi et al. 2024)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThis project was undertaken as a part of the short-term studentship program conducted by the Indian Council of Medical Research (ICMR),on submission and approval of the project report, the student was provided with a stipend of INR 25,000/month for two months by ICMR. We would like to thank the Head of the department to allow us to conduct the study in the specimen storage room.\n\n\nReferences\n\nCDC: Medical Management Guidelines for Formaldehyde. CAS# 50-00-0 UN# 1198, 2209 (formalin).n. d.\n\nChan YJ, Yuan TH, Sun HC, et al.: Characterization and Exposure Assessment of Odor Emissions from Laser Cutting of Plastics in the Optical Film Industry. Aerosol Air Qual. Res. 2016; 16: 2216–2226. Publisher Full Text\n\nChen SS, Cheng CY, Wei CC, et al.: Simultaneous removal of NO and SO2 by high-temperature fluidized zero-valent iron processes. J. Air Waste Manag. Assoc. 2007; 57(3): 303–308. PubMed Abstract | Publisher Full Text\n\nDela Cruz M, Christensen JH, Thomsen JD, et al.: Can ornamental potted plants remove volatile organic compounds from indoor air? — a review. Environ. Sci. Pollut. Res. 2014; 21(24): 13909–13928. PubMed Abstract | Publisher Full Text\n\nGahukar S, Ramteke U, Majumdar D, et al.: Prevalence of formaldehyde in indoor air of gross anatomy laboratory and cadaver storage room of a medical college. J. Environ. Occup. Sci. 2014; 3: 181–185. Publisher Full Text\n\nHomwutthiwong K, Ongwandee M: Investigation of Formaldehyde in Gross Anatomy Laboratory: Area-Based and Exposure Levels, Ventilation, Health Risk and Clinical Symptoms. App. Envi. Res. 2017; 39(3): 77–90. Publisher Full Text\n\nJoshi A, Punja D, Punja R: Can indoor plants reduce formaldehyde levels in the anatomy dissection hall? A study to evaluate the practicality of using plants in reducing formaldehyde level. [Dataset]. figshare. 2024. Publisher Full Text\n\nKim KJ, Kil MJ, Song JS, et al.: Efficiency of Volatile Formaldehyde Removal by Indoor Plants: Contribution of Aerial Plant Parts versus the Root Zone. J. Am. Soc. Hortic. Sci. 2008; 133: 521–526. Publisher Full Text\n\nNielsen GD, Larsen ST, Wolkoff P: Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment. Arch. Toxicol. 2017; 91(1): 35–61. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOnyeka OC, Chiemerie MS, Ozoemena MS, et al.: Effects of formaldehyde inhalation on cardiopulmonary functions on medical students of College of Health Sciences, Nnamdi Azikiwe University during dissection classes. A J. Physiol. Biochem. Pharmacol. 2018; 7(2): 86–94. Publisher Full Text\n\nParthasarathy S, Maddalena RL, Russell ML, et al.: Effect of temperature and humidity on formaldehyde emissions in temporary housing units. J. Air Waste Manag. Assoc. 2011; 61(6): 689–695. PubMed Abstract | Publisher Full Text\n\nShaham J, Bomstein Y, Gurvich R, et al.: DNA-protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde. Occup. Environ. Med. 2003; 60(6): 403–409. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShiraishi N: Levels of formaldehyde, phenol and ethanol in dissection room air and measures for reduction. Jpn J. Occup. Med. Traumatol. 2006; 54: 1–10.\n\nTeiri H, Pourzamzni H, Hajizadeh Y: Phytoremediation of Formaldehyde from Indoor Environment by Ornamental Plants: An Approach to Promote Occupants Health. Int. J. Prev. Med. 2018; 9: 70. Publisher Full Text\n\nWolverton BC, Wolverton JD: Plants and soil microorganisms: removal of formaldehyde, xylene, and ammonia from the indoor environment. Journal of the Mississippi Academy of Sciences. 1993; 38(2): 11–15.\n\nZuber M, Corda JV, Souza AD: Formaldehyde concentration in an anatomical dissection room with three different ventilation configurations using computational fluid dynamics. Eng. Sci. 2022; 18: 177–186."
}
|
[
{
"id": "333509",
"date": "05 Nov 2024",
"name": "Kumar Satish Ravi",
"expertise": [
"Reviewer Expertise Anatomy",
"Cytogentics",
"Medical Education",
"Neuroanatomy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview Feedback on Manuscript\nTitle: “Can indoor plants reduce formaldehyde levels in the anatomy dissection hall? A study to evaluate the practicality of using plants in reducing formaldehyde levels”\nThis study presents an interesting and valuable investigation into the potential for using indoor plants to reduce formaldehyde (FA) levels in an anatomy dissection hall, a setting known for its high levels of this toxic substance. The study design, while sound, would benefit from some additional details and clarifications to provide a more comprehensive understanding of the research approach and its potential implications.\nMy remarks:\n1. Description of Formalin/Preservative Used in Cadaver Preservation:\n\n- The manuscript could have been more informative with a clear explanation of the formalin (or other preservative) used in the preservation of cadavers. While formaldehyde is commonly used for this purpose, a brief description of the specific formulation, concentration, and the conditions under which it is used would provide additional context and clarity to the study.\n\n- It is important to clarify whether all cadavers in the study were preserved in the same manner and if variations in formaldehyde concentrations were considered.\n2. Methodology:\n\n- While the methodology is generally well structured, it could benefit from further elaboration. For example, more details about the selection process for the plant species would help readers understand why Dracaena trifasciata, Epipremnum aureum, and Spathiphyllum were chosen over other plants.\n\n- Additionally, the duration of the plant exposure (14 days) and its rationale should be more thoroughly explained. Is this duration based on prior studies, or was it selected based on practical considerations? Longer exposure periods may have yielded more meaningful results, and discussing this would strengthen the interpretation of the findings.\n3. Potential Health Concerns Regarding Plant Species:\n\n- A notable concern is that both Epipremnum aureum (Golden Pothos) and Spathiphyllum (Peace Lily) are known to contain calcium oxalate, which can be toxic and cause allergic reactions or skin irritation in humans. These plants are mildly toxic if ingested and can cause oral irritation, particularly in children and pets.\n\n- Given that these plants will be placed in an environment that involves human activity (i.e., the anatomy dissection hall), the authors should review the safety implications of using these species in such settings. This could include a discussion on the potential for allergic reactions, skin irritation, or other health concerns for individuals who may come into direct contact with the plants.\n\n- It is crucial to address this concern by justifying their use in the study, especially in a setting where students and faculty are working for extended hours. The authors should also explore the potential risks and whether there are safer alternatives available. A more thorough review of the literature on the toxicity of these plants in work environments would be helpful.\n4. References:\n\n- The manuscript cites older studies, which is acceptable to an extent, but it would be beneficial to include more recent references. The field of indoor air quality and phytoremediation is rapidly evolving, and more up-to-date studies could provide additional support for the findings or reveal emerging trends.\n\n- In particular, newer research on plant-based air purification, formaldehyde absorption rates, and indoor air quality in educational settings could be included to strengthen the context and relevance of the study.\n5. Statistical Analysis:\n\n- The statistical analysis is clearly presented, but the interpretation of the p-values and correlations could be made clearer. Specifically, the discussion on the weak positive correlation with formaldehyde levels should be more thoroughly addressed. Given the results, the authors could explore the reasons why certain plant species did not show a significant reduction in FA levels, despite previous studies suggesting their effectiveness. This could involve discussing the environmental factors (e.g., temperature, humidity) or other variables not accounted for in the study.\n6. Conclusion and Future Research:\n\n- The conclusion is well-written and appropriately acknowledges the limitations of the current study. However, it would be beneficial to provide more specific recommendations for future research. For instance, the authors could suggest conducting a follow-up study with a larger sample of plants or extended exposure periods to better assess the long-term effectiveness of indoor plants in reducing formaldehyde levels.\n\n- Additionally, exploring how different plant species interact with environmental variables (e.g., light, humidity, temperature) would help refine the understanding of which plants are most effective for reducing air pollutants in real-world settings.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12857",
"date": "03 Dec 2024",
"name": "Rohini Punja",
"role": "Author Response",
"response": "We sincerely thank you for the constructive feedback and have tried to address the concerns as pointed. 1. Description of Formalin/Preservative: Response: We have added a more detailed explanation of the formalin used in cadaver preservation in the Methods section. We have specified the concentration, formulation, and standard preservation conditions used in our anatomy department. We have also added that all cadavers were preserved using the same standardized protocol. \"In this study, we used formalin with a standard concentration of 10% formaldehyde solution, prepared according to our department's established preservation protocol. \"All cadavers were preserved using identical formalin preparation methods to ensure consistency in formaldehyde exposure.\" 2. Methodology: Response: We appreciate the feedback on our methodology. We have justified the rationale for selecting Dracaena trifasciata (Sansevieria), Epipremnum aureum, and Spathiphyllum, including their previously reported air purification capabilities.The duration of 14-day exposure period was due to time constraints and this has been included explaining our practical considerations. We have discussed the potential benefits of longer exposure periods in the limitations and future research sections. \"Plant Selection Rationale: \"We selected these three plant species based on their prior reported capabilities in air purification. Sansevieria trifasciata (Snake Plant), Epipremnum aureum (Golden Pothos), and Spathiphyllum (Peace Lily) have been previously documented in scientific literature for their potential to absorb volatile organic compounds.\" 3. Potential Health Concerns Regarding Plant Species: Response: We acknowledge the important safety considerations raised. We have included in the discussion the potential toxicity of Epipremnum aureum and Spathiphyllum, explaining the ideal placement of plants to minimize direct human contact. Since this was conducted in the specimen storage room and students do not have access to this area, except the staff handling these specimens/cadavers the risk of exposure is minimum though we have to keep these points in mind if we plan to replicate this study in an environment where students would be present. 4.References: Response: We have updated our references with more recent studies on indoor air quality and phytoremediation and included newer research on plant-based air purification, particularly focusing on studies conducted in educational settings after 2018. 17. Matheson S, Fleck R, Irga PJ, Torpy FR. Phytoremediation for the indoor environment: a state-of-the-art review. Rev Environ Sci Biotechnol. 2023;22(1):249-280. doi: 10.1007/s11157-023-09644-5. Epub 2023 Feb 27. PMID: 36873270; PMCID: PMC9968648. 18. Peterson G, Jones T, Rispoli D, Haddadi S, Niri V. Investigation of simultaneous volatile organic compound removal by indoor plants using solid phase microextraction-gas chromatography-mass spectrometry. RSC Adv. 2023 Sep 7;13(38):26896-26906. doi: 10.1039/d3ra04015a. PMID: 37692358; PMCID: PMC10483372. 5. Statistical Analysis: Response: We have provided a more detailed interpretation of the weak positive correlations and discussed potential environmental factors that might have influenced plant performance and also explored why our results differed from previous studies, considering variables like temperature, humidity, and room configuration \"The weak positive correlation observed might be attributed to complex environmental interactions. \"Factors such as room temperature (ranging from 26.3-33.4°C), humidity variations (67-85%), and specific room configuration could significantly influence plant performance in formaldehyde absorption.\" 6. Conclusion and Future Research: Response: We have expanded our conclusion to include more specific recommendations for future research; suggestions for follow-up studies with larger plant samples and extended exposure periods and exploration of how environmental variables interact with plant performance in air purification"
}
]
},
{
"id": "333503",
"date": "14 Nov 2024",
"name": "Ranganath Vallabhajosyula",
"expertise": [
"Reviewer Expertise science of learning (metacognition and self-regulated learning)",
"gamification and learning",
"anatomy and cytogenetics and evidence based anatomy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors have conducted an interesting study on role of indoor plants in reducing the formaldehyde levels in the cadaveric labs. Interesting though, there are few questions, that authors would need to address.\nIntroduction: The authors have brought interesting statements on exposure of the quantum of FA concentrations and its effects. At this point, the authors need to emphasize on the composition of the formaldehyde to embalm the cadavers in general as well as experimental site.\n\nMaterial and methods: The authors have explained the size of the plants and arrangement of positions in the cadaver lab. However, they did not indicate the number of specimens (full cadavers, dissected specimens etc, amount of storage solution in the storage areas (if any), size of the storage units and chambers at the experimental site. It is suggestible to add this information in the manuscript. Results: The authors have mentioned that the arrangement of plants is equidistant from one another. However, did the authors observe the distance between the plants and storage areas? Are the plants arranged equidistantly to storage places? If so, please indicate that in the manuscript and report the correlation. Discussion: Requires improvement particularly on the timeline and rationale of the climatic conditions that the authors have focused on this study. The authors have indicated that they have restricted the movement to minimize the error. What is the permissible limit of movement if any? And did the authors notice any changes then.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12858",
"date": "27 Nov 2024",
"name": "Rohini Punja",
"role": "Author Response",
"response": "We sincerely appreciate the reviewer's thoughtful and constructive feedback, which has provided valuable insights for improving our manuscript. Reviewer Comment on Introduction: Response: We have added the details on formaldehyde composition and information about the standard concentration of formalin used for cadaver preservation in our institution, typically a 10% buffered formaldehyde solution, in the methods section. We have also specified the exact concentration of formaldehyde in the storage solution and its potential contribution to ambient formaldehyde levels. \"In this study, we used formalin with a standard concentration of 10% formaldehyde solution, prepared according to our department's established preservation protocol. All cadavers were preserved using identical formalin preparation methods to ensure consistency in formaldehyde exposure.\" Reviewer Comment on Material and Methods: Response: We acknowledge the importance of providing comprehensive contextual information about the experimental environment to enhance the study's reproducibility. In the methodology section these additional details have been included: - Number of cadaveric specimens: Total of 15 preserved specimens - Storage solution details: 10% buffered formaldehyde solution - Storage unit dimensions: Metal preservation chambers, each approximately 2m x 1m x 1.5m - Total storage area volume: Approximately 21 cubic meters - Distance between plants: 25 cm (as originally stated) - Distance between plants and storage units: Approximately 50 cm - Plant arrangement: Centrally positioned in the storage room to ensure uniform distribution Reviewer Comment on Results: Response: We have modified the results to include specific spatial relationships and added a supplementary analysis examining potential correlations between plant placement and formaldehyde concentration variations: \"Additional spatial analysis revealed subtle variations in formaldehyde concentration relative to plant placement. While plants were arranged equidistantly, micro-variations in ambient formaldehyde levels were observed, suggesting potential localized absorption effects that warrant further investigation.\" Reviewer Comment on Discussion: Response: We have attempted to improve the discussion by providing more context about seasonal conditions during the study (summer season, specific temperature and humidity ranges) and clarifying movement restriction protocols: * No more than 2-3 personnel entries per day * Maximum 5 minutes per entry * Strict protocol to minimize air disturbance"
}
]
}
] | 1
|
https://f1000research.com/articles/13-1249
|
https://f1000research.com/articles/13-1435/v1
|
27 Nov 24
|
{
"type": "Systematic Review",
"title": "Evaluating the Efficacy of Targeted Muscle Reinnervation (TMR) in Extremities Amputations of Pedis Squamous Cell Carcinoma: A Comprehensive Systematic Review, Meta-Analysis, and Meta-regression of Functional and Pain Outcomes",
"authors": [
"Robin Novriansyah",
"Amin Husni",
"Rifky Ismail",
"Yuriz Bakhtiar",
"Faiza Rizky Aryani Septarina",
"Kevin Christian Tjandra",
"Nurul Azizah Dian Rahmawati",
"I Nyoman Sebastian Sudiasa",
"Mohammad Satrio Wicaksono",
"Amin Husni",
"Rifky Ismail",
"Yuriz Bakhtiar",
"Faiza Rizky Aryani Septarina",
"Kevin Christian Tjandra",
"Nurul Azizah Dian Rahmawati",
"I Nyoman Sebastian Sudiasa",
"Mohammad Satrio Wicaksono"
],
"abstract": "Introduction Targeted Muscle Reinnervation (TMR) is an innovative surgical procedure initially designed for upper-limb amputations, which has shown growing potential for improving functional outcomes in below-knee amputees. TMR involves redirecting severed nerves from the amputated limb to nearby residual muscles, allowing these muscles to act as amplifiers for nerve signals, thereby improving prosthetic control. Recent advancements in TMR for below-knee amputations have highlighted its ability to reduce post-amputation complications, such as neuroma pain and phantom limb pain, while offering enhanced control over prosthetic limbs, thus improving mobility and quality of life.\n\nMethods Following PRISMA guidelines, a systematic review was conducted, sourcing studies up to May 2024 from PubMed, Cochrane Library, Scopus, Springer, and Epistemonikos. The analysis included randomized controlled trials (RCTs) and clinical trials. A meta-analysis was performed to assess phantom limb pain reduction, while study quality was evaluated using RoB 2.0, ROBINS-I, and ROBINS-E. Meta-regression examined the influence of variables such as age and sex on pain outcomes.\n\nResults Seven studies, including 363 patients, were analyzed. The meta-analysis showed that TMR significantly reduced phantom limb pain (MD: -1.74; 95% CI: -2.46 to -1.02; P<0.00001; I2=0%). However, the pooled risk ratio for phantom pain incidence (RR: 1.58; 95% CI: 0.61 to 4.11; P=0.35; I2=93%) indicated variable outcomes.\n\nConclusion TMR significantly reduces phantom limb pain and improves prosthetic control, particularly for patients with SCC of the foot, ultimately enhancing their quality of life.",
"keywords": [
"Below-knee amputation",
"targeted muscle reinnervation (TMR)",
"prosthetic control",
"phantom limb pain",
"squamous cell carcinoma (SCC)"
],
"content": "Introduction\n\nTargeted Muscle Reinnervation (TMR) is a pioneering surgical technique that has shown significant promise in enhancing the functional outcomes and quality of life for individuals with below-knee amputations. TMR involves redirecting the severed nerves from the amputated limb to residual muscles, enabling these muscles to serve as biological amplifiers for nerve signals. This reinnervation facilitates more natural and intuitive control of prosthetic devices, allowing for improved mobility and dexterity.1\n\nWhile TMR was originally developed for upper-limb amputations, its application in below-knee amputations has gained traction due to its potential to address common post-amputation challenges such as neuroma pain and phantom limb pain.2 By reinnervating the residual muscles in the lower limb, TMR can provide more precise control signals to advanced prosthetic limbs, resulting in smoother and more coordinated movements. Additionally, the technique has been associated with a reduction in pain and discomfort, which significantly contributes to the overall well-being of the amputee.1\n\nRecent studies have demonstrated the efficacy of TMR in below-knee amputees, highlighting improvements in prosthetic control and a decrease in pain symptoms.3 For patients with squamous cell carcinoma (SCC) of the pedis, TMR might be considered if the treatment involves amputation. Squamous cell carcinoma (SCC) of the foot (pedis) can lead to significant disability, primarily due to the aggressive nature of the cancer and the potential need for extensive surgical intervention.4 TMR can help improve the functionality of prosthetic limbs and reduce pain, thus enhancing the quality of life for amputees.5 It can mitigate some of the disabilities associated with amputation by providing better control over prosthetic devices and reducing phantom limb pain. These findings underscore the potential of TMR to transform the rehabilitation landscape for lower-limb amputees, offering a promising solution for those seeking enhanced functional capabilities and pain relief.6 As research continues to evolve, TMR is poised to become an integral component of post-amputation care, particularly for below-knee amputees seeking to regain optimal mobility and quality of life.\n\n\nMethod\n\nThis review was done following the PRISMA guidelines for systemic reviews and meta-analyses. We comprised original research papers published between 2013 and 2024 with the last search being done on 20th May 2024. The studies that were selected had to meet the inclusion criteria for randomized controlled trials (RCTs) and clinical trials. However, exclusion was made for studies such as technical reports, editor responses, narrative reviews, systematic reviews, meta-analyses, non-comparative studies, in silico studies, in vitro studies or in vivo researches, scientific posters, research proposals or conference abstracts. Besides that, other exclusions included those not published in English language; incomplete data; or failing to look at the relationship between miRNA and PTEN gene expression in OSC in association with survival rates. The selected articles followed PICO guidelines as follows: i) amputees with indications for amputation of the limbs; ii) introduction of targeted muscle reinnervation (TMR) during amputation surgery; iii) conventional surgical methods as comparison; iv) VAS scores for assessment of phantom pain and its occurrence rate.\n\nThe study on which this research is based entailed an extensive search across various databases, such as PubMed, Cochrane Library, Scopus, Springer and Epistemonikos. We used a combination of keywords to maximize the relevant literature we would be able to retrieve: (“Targeted Muscular Reinnervation” OR “TMR”) AND (“Limb Amputation” OR “Extremity Amputation”). The searches encompassed studies from the beginning of the databases up to May 20th, 2024, emphasizing research done in the last ten years. Boolean operators were employed for refining results based on Medical Subject Headings (MeSH) as per National Institutes of Health (NIH) National Library of Medicine browser guidelines. To manage all these studies, the authors’ library used Mendeley Group Reference Manager. All databases were filtered for only randomized controlled trials and clinical trial research articles.\n\nThe selection process was done by five independent authors (KCT, INSS, NADR, MS) who conducted initial literature screening articles were first assessed by title and abstract followed by removal of duplicates. Then they performed a second round of full-text reviews to check if eligible criteria for inclusion and exclusion were met. Any discrepancies during this process were resolved via discussions with another author (RN, KCT, NA).\n\nIn a Google Spreadsheet, after the last screening, selected studies were datas were extracted and combined. The collected information comprised the author, year of publication, country, design of the study, sample size, mean age of the respondents, VAS score and incidence of no-phantom pain. Five authors (RN, KCT, INSS, NADR and MS) independently carried out the process of data extraction. The main focus was on the post-surgical effectiveness related to VAS scores and incidences of no phantom pains comparison between TMR outcomes with conventional surgical techniques.\n\nThe risk of bias assessment was independently conducted by five authors using established tools. For the randomized controlled trials (RCTs), we applied the Cochrane Collaboration’s Risk of Bias version 2 (RoB-2) tool, which evaluates five key methodological areas: (a) the randomization process; (b) deviations from intended interventions; (c) missing outcome data; (d) measurement of the outcome; and (e) selection of reported results. The assessment outcomes are presented in Figures 5 – 7, with bias categorized as “low risk,” “high risk,” or “some concerns.”\n\nFor non-randomized studies, the risk of bias was assessed using the ROBINS-I and ROBINS-E tools. The ROBINS-E tool considered seven domains, including: (a) bias due to confounding; (b) bias from exposure measurement; (c) bias in participant selection; (d) bias from post-exposure intervention; (e) bias due to missing data; (f) bias from outcome measurement; and (g) bias in the selection of reported results. Similarly, the ROBINS-I tool evaluated seven domains, such as: (a) bias from confounding; (b) bias in participant selection; (c) bias in intervention classification; (d) bias from deviations from intended interventions; (e) bias due to missing data; (f) bias in outcome measurement; and (g) bias in the selection of reported results.\n\nAny disagreements during the assessment process were resolved through discussion. If consensus could not be reached, RN would make the final decision.\n\nWe employed the standardized mean difference (SMD) with 95% confidence intervals (95% CI) to pool continuous outcome variables, using the inverse variance method. Due to the expected heterogeneity from variations in population characteristics and follow-up durations, random-effects models were chosen for this review.\n\nHeterogeneity across studies was assessed using the I-squared (I2) statistic, with I2 values over 25% indicating significant heterogeneity. For data reported as median and interquartile range (IQR) or as median, minimum, and maximum values, we applied formulas from Luo D et al. and Wan X et al. to convert these into means and standard deviations (SD) for pooling in the analysis.\n\nThe initial analysis compared the intervention and control groups based on follow-up time subgroups. While overall, the intervention group showed better functional outcomes, some studies and subgroup analyses revealed contrary results. As a result, we conducted a separate analysis of preoperative and postoperative values to assess the mean difference for each evaluation in both the intervention and control groups. The pooled mean differences from each evaluation were then compared between these groups.\n\nPublication bias was assessed when more than ten studies were available for any given outcome. If asymmetry was detected in the funnel plot, we reviewed PICO and outcome characteristics to determine if it resulted from publication bias or other factors such as methodological variability between studies. All statistical analyses were performed using Review Manager 5.4 from the Cochrane Collaboration. We further assessed the robustness of the outcomes through sensitivity meta-analyses, which included only studies with a low overall risk of bias.\n\nRegression analysis was conducted to explore the relationship between dependent variables and one or more independent variables. Using linear regression, we examined how variables like mean age and sex influenced the relationships found in the study. The selection of these variables was guided by theoretical considerations relevant to the analytical objectives. Jamovi software was used for the regression analysis, ensuring reliable data interpretation.\n\n\nResult\n\nA total of 920 studies were initially identified through database searches, including 155 from PubMed, 13 from Cochrane, 488 from Scopus, 249 from Springer, and 15 from Epistemonikos. After applying publication year and study type filters, 542 studies were excluded during the first round of screening. The remaining 378 studies were imported into the Mendeley Group Reference Manager for further review, applying the inclusion criteria.\n\nOf these, 320 studies were excluded for being off-topic, and 5 were removed due to duplication. The remaining 53 studies were manually screened by the authors, leading to the exclusion of 48 studies for various reasons: 25 had the wrong study design, 15 reported the wrong outcome, 1 used the wrong intervention, 1 had an incorrect comparator, and 4 focused on the wrong procedural indication.\n\nThe full texts of the remaining seven studies were then thoroughly assessed, and all seven were deemed eligible for inclusion. The research selection process is visually summarized in the PRISMA flow chart (Figure 1). The eligibility of these seven studies was confirmed using the Cochrane ROB-2 tool, with all passing the bias assessment. The PRISMA flow chart provides a detailed account of the research selection process.\n\nTable 1 provides a summary of seven studies that explore different interventions for managing residual limb pain, phantom limb pain, and limb function in amputees. These studies originate primarily from the USA and the UK and include a mix of retrospective cohort studies, randomized clinical trials, and clinical trials. Sample sizes range from smaller cohorts of 8 participants to larger groups of up to 100, with both male and female subjects included. The interventions evaluated across these studies include Targeted Muscle Reinnervation (TMR), nerve insertion techniques, and Agonist-antagonist Myoneural Interface (AMI).\n\nThe age of participants varied, with mean ages ranging from the mid-40s to late 50s. The outcomes consistently suggest that TMR and other nerve-related interventions offer promising improvements in reducing pain and enhancing functional outcomes in amputees. However, the effectiveness of these interventions may differ depending on the specific conditions and methodologies used in each study. The diverse mix of study designs and sample populations offers a broad and comprehensive view of current strategies for addressing post-amputation pain and improving function.\n\nAll included trials in this study undergo a detailed evaluation with the ROB-2 risk of bias tool. Three studies raised concerns across multiple domains, particularly due to unclear randomization procedures, missing outcome data, and deviations from the intended interventions. The results of the risk-of-bias assessment are visually presented in Figures 1, 2, and 3, highlighting the methodological strengths and weaknesses identified in the reviewed studies.\n\nThe risk of bias for all included studies was assessed using the Revised Tool for Risk of Bias in Randomized Trials (RoB-2.0) for randomized studies and the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) for non-randomized studies. The findings indicated that all randomized and non-randomized interventional studies had a low risk of bias, while 50% of the non-randomized exposure studies were also classified as having a low risk of bias.\n\nThe bias assessment using the RoB-2.0 tool revealed that the randomized controlled trials (RCTs) were rated “low” across all five evaluated domains. The detailed assessment results are displayed in Figure 2.\n\nThe bias risk assessment using the ROBINS-I tool revealed that the non-randomized controlled trial (non-RCT) was classified as having a “low” risk of bias. However, among the six non-randomized exposure studies, three were found to have a “some concern” risk of bias. Specifically, the study by Lauren et al. (2020) raised concerns in domain 7. The study by O’Brien et al. (2019) had bias issues in domains 1 and 5, while Lu V et al. (2023) showed bias in domains 1, 2, 5, and 6. The remaining three non-randomized exposure studies were deemed to have a “low” risk of bias.\n\nThe bias assessment outcomes are depicted in Figures 3 and 4, providing a visual representation of the results.\n\nFour studies, involving a total of 121 participants, reported outcomes using the Visual Analog Scale (VAS). As shown in Figure 5, the intervention group exhibited a statistically significant improvement, with a pooled mean difference (MD) of -1.74 [95% CI: -2.46 to -1.02, P<0.00001] compared to the control group. The analysis also revealed significant heterogeneity, although the funnel plot in Figure 6 does not show evidence of heterogeneity.\n\nFive studies, involving a total of 346 participants, assessed outcomes related to the absence of phantom pain, which is described as pain that feels like it originates from a body part that is no longer present. As shown in Figure 7, the intervention group had a higher, though not statistically significant, proportion of patients without phantom pain after surgery compared to the control group, with a pooled risk ratio (RR) of 1.58 [95% CI: 0.61 to 4.11, P=0.35]. The analysis also revealed significant heterogeneity, as evidenced by the funnel plot in Figure 8, which indicates true heterogeneity among the studies.\n\nThe meta-regression data provided examines the influence of several predictors (age, sample size, gender) on two outcome variables: Visual Analog Scale (VAS) scores, which measure pain intensity, and the incidence of phantom pain. Here is an interpretation of the results for each predictor within these outcome variables.\n\nVAS score\n\nThe coefficient for age is negative, suggesting that an increase in age might be associated with a slight decrease in VAS scores, indicating lower pain levels. However, the p-value of 0.581 indicates this relationship is not statistically significant. The wide confidence interval further suggests considerable variability, indicating that age may not be a reliable predictor of VAS scores in this context.\n\nThe negative coefficient implies that larger sample sizes might be associated with slightly lower VAS scores. Nevertheless, the p-value of 0.645 shows this result is not statistically significant, and the confidence interval includes zero, further confirming the lack of a significant effect.\n\nThe positive coefficient suggests that males might report slightly higher VAS scores than females. However, with a p-value of 0.193, this association is not statistically significant. The confidence interval also includes zero, indicating the effect is not robust.\n\nFor the female gender, the coefficient is negative, implying that females might report lower VAS scores than males. Still, the p-value of 0.129 is not statistically significant. The confidence interval includes zero, suggesting this effect is also not substantial.\n\nNo phantom pain incidence\n\nThe coefficient is close to zero, indicating the minimal impact of age on phantom pain incidence. The high p-value of 0.876 and the confidence interval spanning zero indicate no significant relationship between age and the likelihood of experiencing phantom pain.\n\nThe coefficient for sample size is also very close to zero, with a p-value of 0.160, suggesting no significant association between sample size and phantom pain incidence. The confidence interval includes zero, further supporting this lack of effect.\n\nThe coefficient is nearly zero, with a p-value of 0.772, indicating no significant effect of male gender on phantom pain incidence. The confidence interval also supports this non-significance.\n\nThe coefficient is negative, suggesting females might have a lower incidence of phantom pain compared to males. The p-value of 0.051 is close to the traditional threshold for significance (0.05), hinting at a potential effect, but it is not definitively significant. The confidence interval almost excludes zero, suggesting a possible trend worth further investigation. The summary of the meta-regression is available in Table 2 and The Q-Q plot of the meta-regression can be seen in below Figure 9 and Figure 10.\n\nMeta-regression analyzes the effect of Age (A), sample size (B), male gender (C), and female gender (D) on the VAS Score.\n\nMeta-regression analyzes the effect of Age (A), sample size (B), male Gender (C), and female gender (D) on the VAS Score.\n\n\nDiscussion\n\nIn Targeted Muscle Reinnervation (TMR) treatment, severely damaged nerves are rerouted to new, redundant muscles that are no longer needed for their original function after an amputation. This procedure successfully reinnervates the muscles, allowing them to respond towards the transferred nerves neural signals transmission.13 Once reinnervated, these muscles contract and produce EMG signals in response to neural commands targeted directly towards the missing limb. For instance, if a user tries to plantar flexion, the transferred nerve stimulates the target muscle in the pedis to transmit EMG signals that control the prosthetic foot.14,15\n\nNeural control signals for movements such as knee and foot flexion are carried through nerves severed by amputation. Without muscle effectors, this vital neural information cannot be used to control prosthetics. The primary aim of Targeted Muscle Reinnervation (TMR) is to create control sites for four key prosthetic functions: dorsal flexion and plantar flexion of the foot, as well as flexion and extension of the knee joint. This is accomplished through innovative nerve transfers to establish new control sites and preserve existing ones for the appropriate prosthetic functions.16 Although prosthetists can typically address these issues with modifications to the prosthesis, consulting a plastic surgeon may offer a more durable solution for soft tissue problems.17\n\nSeveral options are available for improving soft tissue conditions. Rearrangement of local tissue techniques, such as rotation flaps, advancement flaps, or Z-plasty, could free scar contractures. During TMR, proximally based adipofascial flaps are used to expose nerves and target muscles of the upper extremity or chest. This not only thins the tissue around the subcutaneous adipose, enhancing the EMG signal detected on the skin, but also helps place these flaps to isolate individual signals between target muscle segments. Meanwhile, direct lipectomy of circumferential lipofaction is able to reduce the amount of subcutaneous tissue in patients with excessive subcutaneous fat that dampens EMG signals and affects socket fit.17\n\nVAS score\n\nThe Visual Analog Scale (VAS) is widely used to gauge pain intensity. In this meta-analysis, four studies involving 121 participants were reviewed to assess the impact of an intervention on VAS scores. As shown in the forest plot (Figure 9), the intervention group demonstrated a significant improvement in VAS scores, with a pooled mean difference (MD) of -1.74 [95% CI: -2.46 to -1.02, P<0.00001] compared to the control group. This negative mean difference indicates a notable reduction in pain intensity due to the intervention.\n\nThe significance of the results (P<0.00001) highlights the effectiveness of the intervention in reducing pain, as measured by the VAS. The confidence interval (CI) of -2.46 to -1.02 further reinforces the precision of this estimate, with all values suggesting a decrease in pain. The narrow CI boosts confidence in the intervention’s effectiveness.\n\nRegarding heterogeneity, the funnel plot (Figure 10) indicates no significant heterogeneity among the studies. This suggests that the intervention’s effect on VAS scores is consistent across the studies, adding robustness to the findings. The uniformity across studies is important for generalizing the results, implying that the intervention may be broadly effective in various settings and populations with similar outcomes expected.\n\nPhantom pain incidents\n\nPhantom pain, the sensation of pain in a missing limb, is a major issue following amputation. This meta-analysis examined five studies involving 346 participants to evaluate the effect of an intervention on the occurrence of phantom pain. As illustrated in the forest plot (Figure 6), the intervention group had a non-statistically significant higher number of patients without phantom pain compared to the control group, with a pooled risk ratio (RR) of 1.58 [95% CI: 0.61 to 4.11, P=0.35].\n\nThe risk ratio of 1.58 suggests that those in the intervention group are 58% more likely to be free from phantom pain compared to the control group. However, this result is not statistically significant (P=0.35), and the wide confidence interval (0.61 to 4.11) indicates considerable variability in the effect estimate, which reduces the precision and reliability of the intervention’s impact on phantom pain.\n\nThe funnel plot (Figure 8) indicates significant heterogeneity among the studies. This variability suggests that the intervention’s effect on phantom pain may differ across studies due to differences in study design, participant characteristics, intervention types, or other factors. Such heterogeneity makes it challenging to interpret and generalize the findings consistently.\n\nIncluded studies have highlighted various clinical applications of Targeted Muscular Reinnervation (TMR). TMR can be applied to patients with infections, trauma, or oncologic issues in limbs.18 Additionally, TMR has been shown to reduce the need for opioid consumption in amputees.19\n\nTMR addresses chronic residual limb pain and phantom pain by transferring a transected proximal nerve stump to a muscle that is denervated surgically, improving possibility of reinnervation.7 This approach focuses on nerves that are relocated into specific muscle segments to produce distinct electromyographic (EMG) signals, enhancing control over myoelectric prostheses. The goal of TMR is to provide a substantial amount of healthy recovering axons to downstream motor muscle units, resulting in clear and detectable surface EMG signals. Large proximal recipient motor nerves are utilized to allow for formal neurorrhaphy, thus defining the denervation and reinnervation of targeted muscle segments.20–22\n\nThe use of TMR for scc pedis has not been mentioned in many publications and scientific articles, which can provide more information regarding the treatment of scc pedis with TMR techniques.\n\n\nConclusion\n\nTMR successfully reinnervated muscles, preventing phantom and residual pain, thus eliminating the need for opioids. The technique also enhanced control over prosthetics by generating clear electromyographic (EMG) signals. Despite its promise, variability in reported efficacy, as shown in meta-analyses of phantom pain, highlights the need for further research to understand factors contributing to inconsistent outcomes across studies. Additionally, the lack of post-prosthetic EMG assessment limits the evaluation of long-term nerve functionality. While TMR shows great potential, more research is needed to establish its role in SCC and similar conditions.\n\nOn August 5, 2024, this systematic review and meta-analysis was registered with the Open Science Framework (OSF) under the title, “Targeted Muscle Reinnervation (TMR) significantly reduces phantom limb pain and improves functional outcomes in below-knee amputees, including those with squamous cell carcinoma (SCC) of the pedis, by providing better control over prosthetic devices and enhancing overall quality of life” (https://doi.org/10.17605/OSF.IO/FG5B7).\n\n\nEthics approval and consent\n\nThis study does not require any ethical approval and consent.",
"appendix": "Availability of data and materials\n\nNo data is associated with this article.\n\nThe reporting guidelines for this study are available through Mendeley Data. The PRISMA checklist and flowchart can be accessed under the title “PRISMA of Evaluating the Efficacy of Targeted Muscle Reinnervation (TMR) in Extremities Amputations of Pedis Squamous Cell Carcinoma: A Comprehensive Systematic Review, Meta-Analysis, and Meta-Regression of Functional and Pain Outcomes,” with the DOI: 10.17632/38yzc3vcbh.1. 23\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe gratefully acknowledge the support from Universitas Diponegoro through their scholarship program, which made this research possible. Their funding and encouragement have played a crucial role in completing this study, and we are sincerely thankful for their contribution to advancing our work.\n\n\nReferences\n\nCheesborough JE, Souza JM, Dumanian GA, et al.: Targeted muscle reinnervation in the initial management of traumatic upper extremity amputation injury. Hand (N Y). 2014; 9(2): 253–257. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDumanian GA, Potter BK, Mioton LM, et al.: Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann. Surg. 2019; 270(2): 238–246. PubMed Abstract | Publisher Full Text\n\nBowen JB, Ruter D, Wee C, et al.: Targeted Muscle Reinnervation Technique in Below-Knee Amputation. Plast. Reconstr. Surg. 2019; 143(1): 309–312. PubMed Abstract | Publisher Full Text\n\nStanganelli I, Spagnolo F, Argenziano G, et al.: The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts. Cancers (Basel). 2022; 14(2): 377. Published 2022 Jan 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlexander JH, Jordan SW, West JM, et al.: Targeted muscle reinnervation in oncologic amputees: Early experience of a novel institutional protocol. J. Surg. Oncol. 2019; 120(3): 348–358. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEberlin KR, Brown DA, Gaston RG, et al.: A Consensus Approach for Targeted Muscle Reinnervation in Amputees. Plast. Reconstr. Surg. Glob. Open. 2023; 11(4): e4928. Published 2023 Apr 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMioton LM, Dumanian GA, Shah N, et al.: Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees. Clin. Orthop. Relat. Res. 2020; 478(9): 2161–2167. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Brien AL, Jordan SW, West JM, et al.: Targeted Muscle Reinnervation at the Time of Upper-Extremity Amputation for the Treatment of Pain Severity and Symptoms. J. Hand. Surg. Am [Internet]. 2021; 46(1): 72.e1–72.e10. PubMed Abstract | Publisher Full Text\n\nLu V, Zhou A, Krkovic M: Variation on a technique for the intra-muscular insertion of nerve endings to minimise neuropathic and residual pain in lower limb amputees: a retrospective cohort study. Eur. J. Orthop. Surg. Traumatol [Internet]. 2023; 33(4): 1299–1306. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSong H, Israel EA, Gutierrez-Arango S, et al.: Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation. Commun. Med. 2022; 2(1). Publisher Full Text\n\nChang BL, Mondshine J, Attinger CE, et al.: Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees. Plast. Reconstr. Surg. 2021; 148(2): 376–386. PubMed Abstract | Publisher Full Text\n\nKubiak CA, Kemp SWP, Cederna PS, et al.: Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Plast. Reconstr. Surg. 2019; 144(3): 421e–430e. PubMed Abstract | Publisher Full Text\n\nElsberg CA: EXPERIMENTS ON MOTOR NERVE REGENERATION AND THE DIRECT NEUROTIZATION OF PARALYZED MUSCLES BY THEIR OWN AND BY FOREIGN NERVES. Science. 1917; 45(1161): 318–320. PubMed Abstract | Publisher Full Text\n\nO’Donovan MJ, Pinter MJ, Dum RP, et al.: Kinesiological studies of self- and cross-reinnervated FDL and soleus muscles in freely moving cats. J. Neurophysiol. 1985; 54(4): 852–866. PubMed Abstract | Publisher Full Text\n\nGordon T, Stein RB, Thomas CK: Innervation and function of hind-limb muscles in the cat after cross-union of the tibial and peroneal nerves. J. Physiol. 1986; 374: 429–441. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuiken TA, Barlow AK, Hargrove L, et al.: Targeted Muscle Reinnervation for the Upper and Lower Extremity. Tech. Orthop. 2017; 32(2): 109–116. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCheesborough JE, Smith LH, Kuiken TA, et al.: Targeted muscle reinnervation and advanced prosthetic arms. Semin. Plast. Surg. 2015; 29(1): 62–72. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnderson SR, Wimalawansa SM, Roubaud MS, et al.: Targeted muscle reinnervation following external hemipelvectomy or hip disarticulation: An anatomic description of technique and clinical case correlates. J. Surg. Oncol. 2020; 122(8): 1693–1710. PubMed Abstract | Publisher Full Text\n\nFrantz TL, Everhart JS, West JM, et al.: Targeted Muscle Reinnervation at the Time of Major Limb Amputation in Traumatic Amputees: Early Experience of an Effective Treatment Strategy to Improve Pain. JB JS Open Access. 2020; 5(2): e0067. Published 2020 May 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuiken TA, Dumanian GA, Lipschutz RD, et al.: The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthetics Orthot. Int. 2004; 28(3): 245–253. Publisher Full Text\n\nKuiken TA, Li G, Lock BA, et al.: Targeted muscle reinnervation for real-time myoelectric control of multifunction artificial arms. JAMA. 2009; 301(6): 619–628. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuiken TA, Miller LA, Lipschutz RD, et al.: Targeted reinnervation for enhanced prosthetic arm function in a woman with a proximal amputation: a case study. Lancet. 2007; 369(9559): 371–380. Publisher Full Text\n\nNovriansyah R, Husni A, Ismail R, et al.: PRISMA of Evaluating the Efficacy of Targeted Muscle Reinnervation (TMR) in Pedis Squamous Cell Carcinoma Below-Knee Amputations: A Case Report, Comprehensive Meta-Analysis, and Meta-Regression of Functional and Pain Outcomes.Publisher Full Text"
}
|
[
{
"id": "344270",
"date": "11 Dec 2024",
"name": "Muhammad Luqman Labib Zufar",
"expertise": [
"Reviewer Expertise Orthopaedic"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction: - The introduction is well written. However, there are no clear aims of the following study\nMethods: - Exclusion criteria included \"failing to look at the relationship between miRNA and PTEN gene expression in OSC in association with survival rates\". The statement seems out of place - PICO should also mention [lower] limb - Not all studies included has a comparison - \"All databases were filtered for only randomized controlled trials and clinical trial research articles\". However, there are cohorts in the included study\nResult: - Well described\nDiscussion: - Discussion mainly repeat the result, it needs to be deepened especially regarding pedis SCC\nGeneral: - There are some typos, spelling, and sentences should be revised -The abbreviation should be checked; there are some repetitive terms in content (TMR are mentioned numerously) - Author should be written based on the last name (Lauren et al --> Mioton et al)\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1435
|
https://f1000research.com/articles/12-302/v1
|
20 Mar 23
|
{
"type": "Research Article",
"title": "Lycium barbarum (Goji berry) mouthwash is a viable alternative to 0.2% chlorhexidine gluconate for managing chronic periodontitis: a randomized clinical trial",
"authors": [
"Amee Sanghavi",
"Laasya Shettigar",
"Aditi Chopra",
"Ashmeet Shah",
"Richard Lobo",
"Padmaja A Shenoy",
"ShivaPrasada Gadag",
"Usha Y Nayak",
"Mangalore Shravya S",
"Shobha Ullas Kamath",
"Prajna P Nayak",
"Amee Sanghavi",
"Laasya Shettigar",
"Ashmeet Shah",
"Richard Lobo",
"ShivaPrasada Gadag",
"Usha Y Nayak",
"Mangalore Shravya S",
"Shobha Ullas Kamath",
"Prajna P Nayak"
],
"abstract": "Background: Removal of the microbial deposits (plaque and calculus) by performing effective scaling and root planing (SRP) is the primary and fundamental requirement for managing periodontal disease. Various adjuncts with antimicrobial, antioxidant, and anti-inflammatory properties are used as adjuncts to SRP for managing chronic periodontitis. However, with a rapid rise in antimicrobial resistance to several antimicrobial agents along with the increased risk of adverse effects, the use the conventional chemotherapeutic agents for managing periodontal disease is slowly declining. Hence, there is a urgent need to explore new plant-based products for treating periodontal disease. Lycium barbarum (L. barbarum), or goji berry, has recently gained popularity for managing chronic inflammatory and infectious diseases. However, its efficacy in managing periodontal diseases has never been explored. Hence the present study aims to evaluate the efficacy of L. barbarum mouthwash along with SRP compared to chlorhexidine for managing chronic periodontitis. Methods: The study is designed as a randomized clinical trial with 57 adult participants (Males:29; Females:28) with chronic periodontitis. The participants were divided randomly into two groups: One group used L. barbarum mouthwash and the other group used ‘0.2% chlorhexidine gluconate’ mouthwash. The changes in the gingival index (Gi), plaque index (Pi), bleeding on probing (BOP), clinical attachment loss (CAL), probing pocket depth (PPD), microbial load, and antioxidant levels (protein thiol) in saliva were noted at the baseline, at 15 days and one month. Results: A statistically significant difference was noted in the Pi (P-value = 0.791), Gi (P-value= 0.594), PPD (with P-value= 0.134), and microbial levels (P-value = 0.188) in both groups from the baseline. The protein thiol levels in saliva were increased only in the goji berry group. Conclusion: L. barbarum mouthwash along with SRP was found to be effective in managing periodontal disease.",
"keywords": [
"Periodontitis",
"Periodontal disease",
"Oral health",
"Dental Hygiene",
"Lycium Barbarum",
"Goji berry",
"Mouthwash",
"Chlorhexidine",
"Herbal",
"Antioxidants"
],
"content": "Introduction\n\nPeriodontitis is defined as a chronic immuno-inflammatory multifactorial disease that affects the soft tissue around the teeth.1 Periodontitis is considered the 6th most common disease that affects approximately 20–50% of the adult population worldwide.2 It is more prevalent in males as compared to females. It is primarily caused by the interaction of the gingival tissues with the microorganisms in the oral biofilm. This host-microbial interaction triggers a massive influx of various pro-inflammatory mediators, microbial byproducts, proteolytic enzymes, and free reactive oxygen species, in the gingival and periodontal tissues leading to periodontal tissue destruction.3–6 Due to increased oxidative stress during periodontal disease, it is also referred to as free radical-mediated tissue injury.7 Some of the common putative periodontal microbes associated with chronic periodontitis are Porphyromonas gingivalis, Tanerella forsythia, Treponema denticola, Campylobacter rectus, and Fusobacterium nucleatum.7 Apart from the microbial etiology, other risk factors that exaggerate periodontal inflammation include smoking, diabetes mellitus, HIV, nutritional deficiency, medications, poor oral hygiene, and genetics.8\n\nThe primary and most vital step to control periodontal inflammation is to control the biofilm formed around the teeth by effective mechanical debridement by either hand or machine-driven instruments.9,10 Effective scaling and root planning (SRP) can reduce gingival inflammation, thereby preventing disease progression and restoring gingival health.11 However, mechanical debridement is technically demanding, as many times removal of hard and soft tissue deposits from pockets greater than five mm becomes challenging. Additionally, it is difficult to completely remove the smooth or burnished calculus from deep and circuitous periodontal pockets, furcation areas, root concavities, and irregular roots owing to a lack of good visibility and accessibility to such areas.12,13 Hence SRP in deep and tortuous pockets often exhibits residual subgingival biofilm and calculus, thereby warranting a need for additional periodontal therapy.12–15\n\nThe efficacy of professional prophylaxis is also dependent on the individuals’ compliance and motivation to maintain a meticulous oral care regime and effective plaque control at home.16 SRP alone may not be sufficient to maintain the required plaque control if patient compliance is poor and the patient does not effectively follow oral hygiene instructions at home. Studies have shown that even after a good plaque control regime, posterior, palatal, and lingual surfaces of the teeth will retain some amount of plaque, and this warrants the need for adjuncts to regular toothbrushes at home.11,17–23\n\nChemical plaque control measures are often advocated as adjuncts to professional oral prophylaxis and daily home care.24 Various chemical plaque control agents that have antimicrobial and anti-inflammatory are being used in the form of mouthwash, gels, gum paints, fibers, varnishes, microspheres, chips, tablets, powder, and capsules for managing gingivitis and chronic periodontitis. Among all these agents, chlorhexidine gluconate is considered the most popular and routinely used agent for managing periodontal disease. However, prolonged use of chlorhexidine is contraindicated owing to various side effects like altered taste sensation, staining of the teeth and soft tissues such as tongue and mucosa, increased calculus formation, and parotid gland swellings.25 Chlorhexidine has also been shown to have cytotoxic effects on the gingival fibroblasts,26 periodontal ligament,27 and osteoblastic cells.28 Recent studies have even reported the emergence of antimicrobial resistance among oral bacteria to chlorhexidine molecules.29 Thus, there is an emerging trend to use natural and herbal extracts for treating periodontal disease. Herbal extracts from neem, Tulsi, guava, green tea, turmeric, curcumin, pomegranate, and many more plants have been tried to effectively treat gingival and periodontal diseases.30–34 Recently, goji berry, commonly known as Wolfberry, Himalayan goji, or Tibetan goji, has gained a lot of popularity due to its strong antioxidant and anti-inflammatory properties.\n\nGoji berry is scientifically known as Lycium barbarum (L. barbarum). L. barbarum is native to southeast Europe, China, and Asia. It comes under the family of Solanaceae.35 The fruit in the form of berries is consumed in both fresh and dried form. L. barbarum contains abundant antioxidants such as scopoletin, vitamin C analogs, carotenoids (zeaxanthin and β-carotene), flavonoids, quercetin, etc. These constituents have powerful antioxidant, immuno-modulating and anticancer properties.36–46 The stems and berries of goji berry plant was effective against many various Gram-negative bacteria and Gram-positive bacteria. Soesanto et al (2021) also showed that ethanolic of L. barbarum was effective against caries-causing bacteria (Streptococcus. Mutans) and P. gingivalis at 100 μg/mL.47 Previous in-vitro studies have also found that the minimal inhibitory concentration (MIC) of L. barbarum was comparable to chlorhexidine, however, its efficacy was less as compared to the antibiotic doxycycline.48,49 At 50 μg/mL, ethanolic extract of goji berry could inhibit most of the periodontal pathogens.48,49\n\nHowever, no clinical study has yet assessed the effectiveness of goji berry mouthwash as an adjunct to SRP for the management of periodontal diseases. Therefore, this clinical study aims to evaluate the efficacy of L. barbarum mouthwash along with SRP for patients with chronic periodontitis compared to chlorhexidine for the first time.47\n\n\n\n1. To evaluate the effect of L. barbarum mouthwash on the Pi, Gi, BOP, PPD, and CAL at baseline, 15 days and one month compared to 0.2% chlorhexidine gluconate mouthwash.\n\n2. To evaluate and compare the change in the protein thiol levels in saliva at 15 days, and one month compared to baseline.\n\n3. To evaluate and compare the reduction in the microbial count at end of one month compared to baseline in participants using L. barbarum mouthwash compared to chlorhexidine mouthwash\n\n\nMethods\n\nThe study was designed as a randomized, double-blind single-centered parallel arm study with an allocation ratio of 1:1. The study was conducted at Manipal’ from 2019 to 2020 following the “Helsinki Declaration of 1975 (as revised in 2000)”. The trial was initiated after receiving ethical clearance from the Kasturba Medical Hospital Institutional Ethics Committee with IEC no 117/2019. The trial has been registered at the ‘Clinical trial registry (CTRI/2019/05/019042)’ and was done following the CONSORT and SAGER guidelines (Figures 1 and 2).48 The step in the clinical trials are explained as follows:\n\nFormulation of mouthwash: The mouthwash was prepared at the “Manipal College of Pharmaceutical Sciences, Manipal”. L. barbarum mouthwash was prepared by preparing an ethanolic extract of dried goji berry using Soxhlet’s method and dissolving the accurately 50 ug/ ml of weighed goji berry extract for formulating the mouthwash as described previously.49 A concentration of 50 ug/ml was mixed in 1.15 of 100% alcohol and then homogenized using of 15% glycerol. To this around 15% propylene glycol, 1% Tween solution was added to formulate the mouthwash. 0.1% menthol was added to the adjust to the taste of the mouthwash. The volume was adjusted to 100% by using distilled water. 100% alcohol was added to serve both as a preservative and a dissolvent.\n\nAssessment of stability of mouthwash\n\nThe shelf life of the mouthwash was measured as per the ICH guidelines and the samples were tested for three months under three different conditions: “35°±2% C with relative humidity of 60% ± 5%; 25°C± 2°C and relative humidity: 60% ± 5%; and 40°C ± 2°C with a relative humidity of 75% ± 5%”. The mouthwash was kept in opaque plastic bottles and one of the bottles was kept in the stability compartment (Thermo lab, India). The samples were analysed at baseline, one, two, and three months by visual observation and UV spectrum analysis (Shimadzu UV-1601PC, Japan) and analysed for its physical parameters and stability. The mouthwash showed no change in the colour, odour, consistency, or no phase separation at three months. The sample showed no change when observed under the ultraviolet analysis at 274 nm. This indicated that the mouthwash was stable till the end of three months (Table 1).\n\nClinical study design\n\nAround ninety subjects aged 20 to 50 years (both male/females) visiting the outpatient department were screened for the presence of chronic periodontitis according to the following exclusion and inclusion criteria:\n\nInclusion criteria:\n\n1. Participants in age group of 20-50 years diagnosed with Stage 1 to stage II generalized periodontitis (Grades A to B).\n\n2. Participants with a minimum of 24 functional teeth.\n\nExclusion criteria:\n\n1. Individuals with severe periodontitis (localized and generalized or Stage III and Stage IV) were excluded.\n\n2. Participants with any allergic reactions to chlorhexidineg\n\n3. Participants with any systemic diseases such as hypertension, diabetes mellitus, cardiovascular, renal, and neurological diseases.\n\n4. Participants on any concurrent medications\n\n5. Participants currently using anti-inflammatory, antibiotics, or analgesics in the last six months\n\n6. Pregnant or lactating mothers\n\n7. Participants with any oral abusive habits such as smoking, alcohol, betel nut chewing, gutka, paan, supari, areca nut\n\n8. Participants who had undergone any periodontal treatment/surgery in the last six months\n\n9. Participants undergoing orthodontic treatment.\n\n10. Participants using any other oral hygiene agents (mouthwash or gels) will be excluded to remove confounding bias arising due to the difference in plaque control measures.\n\nAll participants who satisfied the above-mentioned criteria were recruited after obtaining an oral and written signed informed consent.\n\nAfter screening the participants, around 60 participants were recruited after obtaining oral and written informed consent. This sample size was based on p-value <0.05, alpha value = 0.05 two-tailed, power = 0.8, and the effect size = 0.7. Of 60 participants, three participants refused the to take part in the study after scaling, and the remaining fifty-seven participants were randomly allocated using the computer-generated random sequence to either the test group (L. barbarum, n = 30) or the control group (0.2% chlorhexidine gluconate mouthwash, n = 27). The allocation of participants into two groups was done by an investigator who was not the part of the either samples collection, periodontal therapy or periodontal examination. Following recruitment, all participants were assigned to another investigator who was blinded about the randomization and grouping. The participants were also blinded about their group. Following grouping, the following biologic samples were collected:\n\na. Microbiology plaque sample collection\n\nThe plaque from the subgingival region was collected from the pocket with the maximum probing depth in each quadrant using a sterile site-specific Gracey curette. After collection, the curette was gently submerged in a reduced transport medium (Thioglycolate bath) for testing the total colony Forming Units (CFU). The number of colonies were calculated on the plated blood agar and then converted to CFU/mL using the following formula: CFU/mL = (no. of colonies × dilution factor)/volume of the culture plate.\n\nb. Saliva Collection\n\nFollowing plaque collection, a stringent method for saliva collection was followed. All participants were requested to sit comfortably in an upright position. Following this, around 2ml of saliva was collected by the ‘spitting method’ and without any stimulation.50 All participants were requested toward spiting the saliva into an Eppendorf vial. The collected saliva was then stored immediately in a refrigerator at -80 degree Celsius. The Eppendorf tubes used to store saliva samples were numerically marked according to the participant number. The saliva collected was sent for biochemical analysis for evaluation of the protein thiol levels using Ellman's Reagent. The absorbance of the agent was measured after incubation at room temperature at 412 nm for around five minutes and the concentration of protein thiol was determined with the standard curve of glutathione.\n\nc. Examination of the clinical periodontal parameters\n\nFollowing saliva sample collection, a periodontal examination was done for all the sextants. The following periodontal parameters were recorded: Gi by Loe & Silness, 1963; percentage of sites with BOP; PI by Silness & Loe 1964; PD and CAL. All the clinical evaluation was done by the investigator who was blinded about the patient’s grouping. The BOP, PPD, and CAL were recorded by Williams periodontal probe (Hu-Friedy, USA). The sites with BOP were checked by noting the presence and absence of bleeding on all four surfaces (buccal, lingual, mesial, and distal) for all the teeth. The percentage of sites with BOP was considered by the percentage of the teeth with BOP to the total teeth present. The PPD and CAL were calculated at buccal, mesial, distal, and lingual. The deepest pocket depth at each surface was recorded. The average of each surface was considered as the reading for that tooth. The mean PPD and CAL were assessed by adding the reading from each tooth and dividing it with the total number of teeth.\n\nFollowing periodontal examination and sample collection, a thorough SRP was initiated for all the participants. The scaling was assessed by the supervisor to ensure the complete removal of plaque and calculus has been achieved. All patients were educated to brush their/teeth in modified bass technique for two minutes twice daily, to nullify any confounding effects arising due to differences in the oral hygiene measures. All participants were given the opaque amber color bottle which were coded (AX or BX). This was done to blind the patients and investigators regarding the type of mouthwash given to the participants. All patients were instructed to use 10 ml mouthwash diluted with 10 ml of water twice a day for a month. Patients were recalled after 15 days and one month for revaluation. At each recall visit Pi, Gi, % of sites with BOP, CAL, and PPD were noted. The plaque from same site and saliva samples were collected at each recall visit. The investigation for each participant, at each recall visit, was done by the same investigator.\n\nData obtained was analysed by the ‘SPSS version 26.0, IBM’. The descriptive data such as the frequency and for categorical data; mean and standard deviation for all the numerical data was analysed using ‘Kolmogorov–Smirnov test’. The normality of the distribution was checked for all variables. The inter-group comparisons of all the assessed outcomes were done using an ‘independent sample t-test’. The comparisons between the goji berry mouthwash and chlorhexidine mouthwash was done to measure any significant increase/reduction from baseline to 15 days and one month using Repeated measures ANOVA. Intergroup comparison of reduction of all the variables at follow-up was done using ANCOVA after adjusting the respective baseline scores. The P-value of less than 0.05 was considered to be significant.\n\n\nResults\n\nThe study results showed that the mean age of study participants in the test group was 35.42 ± 11.79 years and in the controls was 32.12 ± 12.85. The gender wise distribution in the test group was Males: 16; Female: 14 and Control group was Males: 13; Females: 14 (Table 2). The comparison between goji berry mouth group and chlorhexidine group for of all the study variables was found to have no significant differences in the mean values for Pi (P = 0.470), Gi (P = 0.239), BOP (P = 0.450), PPD (P = 0.216), CAL (P = 0.220), and Microbial level (P = 0.251) (Table 3). The intra-group comparison using the ‘repeated measures of ANOVA with Greenhouse Geisser correction’ followed by a ‘post-hoc analysis with Bonferroni adjustment’. This showed that the mean PPD, Pi, and Gi, was changed from baseline to one month in both the control and test groups. The CAL was reduced significantly only in the chlorhexidine group compared to the goji berry group (Table 3, Table 4 and Figure 3). A significant difference was noted in the antioxidant levels (protein thiol) in saliva in the goji berry group at the end of one month. No change in the salivary antioxidant level was noted in the chlorhexidine group. No significant differences were reported in the log-transformed microbial CFU counts in both groups at any given time. In the case of the test group, the mean Pi reduced from 1.6 ± 0.38 at baseline and was 0.89 ± 0.17 at one month. However, in the case of the goji berry mouthwash, the mean PPD was reduced during the 15-day follow-up (1.73 ± 0.45) compared to baseline (2.76 ± 1.06). The intergroup comparison at one-month follow-up (15 days and one month) after adjusting the respective baseline scores was done using ANCOVA. The control group had a significant reduction in CAL (P = 0.001) as compared to the test group. There were no differences seen in the mean values for Pi (P = 0.791), Gi (P = 0.594), PPD (P = 0.134), protein thiol levels (P = 0.211), and microbial levels (P = 0.188) between the two groups (Table 4). No harms were reported by any patient. One patient reported bitter taste of the mouthwash and discontinued the mouthwash.\n\n# P-value for inter-group comparisons (independent sample t-test);\n\n¥ P-value for intra-group comparisons (Repeated measures ANOVA).\n\n\nDiscussion\n\nThe present study is the first clinical trial aimed to evaluate the role of goji berry in treating any dental diseases. The study evaluated the effectiveness of goji berry mouthwash compared to chlorhexidine for managing chronic periodontitis in both males and female patients. Based on the results, it was noted that goji berry mouthwash can control the gingival inflammation, BOP, and plaque formation at 15 days following SRP with statistically significant difference compared to chlorhexidine group. A significant in the Gi, Pi, BOP, PPD was noted in participants using goji berry mouthwash. To our knowledge, this is first clinical trial comparing the potential of L. barbarum and chlorhexidine (gold standard antimicrobial agent) as an adjunct to SRP for the management of chronic periodontitis. The most significant outcome was the statistically significant increase in the protein thiol levels in saliva in the goji berry group alone, suggesting the advantage of using the goji berry mouthwash over chlorhexidine. This could be attributed to powerful antioxidants in goji berry mouthwash compared to chlorhexidine.\n\nGoji berry is considered a ‘superfood’ with good antimicrobial, anti-inflammatory, and antioxidant properties. The constituents of L. barbarum have been tried for various inflammatory and infectious disease, however its role in treating periodontal inflammation has not been explored. The use of L. barbarum could improve the local antioxidant levels and this in turn helps in controlling the clinical symptoms of inflammation in chronic periodontitis. The study is crucial, especially with the emergence of resistance to chlorhexidine molecules among oral bacteria and numerous side effects of using chlorhexidine for long time.51 Recent systematic reviews have shown that there are limited benefits of using chlorhexidine gluconate in patients with chronic periodontitis owing to the development of resistance among oral bacteria to chlorhexidine molecule and cytotoxicity to soft tissues by chlorhexidine.52 Hence the use of plant-based products with antioxidant and anti-inflammatory properties is advocated to control the local oxidative stress in the gingival tissues and preclude the harmful effects of chlorhexidine.53\n\nGoji berry has numerous antioxidants, which could be utilized to combat the proinflammatory mediators and oxidative stress in the periodontal tissues.54–56 Some of the important antioxidants in L. barbarum are the Lycium barbarum polysaccharides (LBPs), caffeic acid, coumaric acid, scopoletin, linoleic acid, zeaxanthin dipalmitate, kaempferol, caffeoylquinic and coumaric acid.55–57 Studies have also identified different types of flavonoids such as catechin, epicatechin, and quercetin in goji berries. Flavonoids have a good antimicrobial effect on the various periodontal pathogen and this could justify the reduction in the PI and control the gingival inflammation in participants using goji berry mouthwash. The alcoholic group (-OH) in the goji berry is also another antimicrobial agent that can control the microbial growth in oral biofilm.58 Goji berry also contains monoterpenes (like sabinene, phellandrene, γ-terpinene), phenolic acid (chlorogenic acid), citric acid, tartaric acid, oxalic acid, malic acid, and vitamin C. These compounds have shown superior anti-inflammatory and antibacterial properties.59 LBP in goji berry is also a potent inhibitor of proinflammatory cytokines. It can inhibit matrix metalloproteinase (MMP-1), Tumor necrosis factor, Interleukin-2, and PGE2. This can helps to control connective tissue destruction, which is a crucial aspect in the progression of periodontal disease. Goji berries can help to improve fibroblast healing and increase the production of Type I collagen.41,60 This can be attributed to the ability to reduce gingival inflammation and release of various antioxidants. Chlorogenic acid in the goji berry can even inhibit nitric oxide and inducible nitric oxide synthase which are some of the vital pathways activated during periodontal inflammation.61–63 At the molecular level, the polysaccharides in the goji berries (LBP) influence the ‘antigen-presenting cells’ such as dendritic cell. This improves the adaptive immune response at the site of inflammation and control tissue destruction.61 Direct effect of chlorogenic acid, yet another important constituent in goji berry, on the oxidative stress-induced secretion of proinflammatory cytokines and mRNA expression has also been proven.62,63\n\nBased on our results and exitsing evidence, it can be concluded that goji berry can be an effective adjunct to oral prophylaxis compared to chlorhexidine in patients with chronic periodontitis.64,65 Although our study has proven that goji berry mouthwash is an effective adjunct to SRP for managing periodontitis, future studies should compare the efficacy of goji berry with other herbal or plant-based adjuncts with long term follow up. One should also note that the study tested the role of goji berry for only a short recall time, as prolonged exposure to chlorhexidine mouthwash is associated with many side effects. Future studies can explore the effect of goji berry on longer recall visits. Future studies can also evaluate the effect of L. barbarum on specific periodontal pathogens such as red complex bacteria or P. gingivalis or specific biomarkers for periodontitis.\n\n\nConclusion\n\nL. barbarum is a promising ‘superfood’ with many potential health benefits. It has antioxidant and antimicrobial properties that can be utilized for developing novel formulations for treating patients with chronic periodontitis. L. barbarum mouthwash effectively reduced plaque scores, gingival inflammation, and bleeding on probing. Goji berry can be tried instead of chlorhexidine gluconate for managing periodontal disease.\n\nThe study was conducted after receiving ethical approval from Kasturba Medical College and Kasturba Hospital Ethic committee with IEC no: IEC no 117/2019. The trial has been registered at the ‘Clinical trial registry (CTRI/2019/05/019042)’.",
"appendix": "Data availability\n\nFigshare. Data on study titled: Lycium barbarum (Goji berry) mouthwash is a viable alternative to 0.2% chlorhexidine gluconate for managing chronic periodontitis: a randomized clinical trial. DOI: https://doi.org/10.6084/m9.figshare.21834939.v1. 65\n\nThis project contains the following data:\n\n- CONSORT checklist\n\n- Study protocol\n\nFigshare. Goji berry mouthwash as alternative to chlorhexidine for managing chronic periodontitis. DOI: https://doi.org/10.6084/m9.figshare.21780164.v1. 64\n\nThis project contains the following data:\n\n- Study data\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThe datasets related to our study is also available with the corresponding author and can be shared on reasonable request via email to aditi.chopra@manipal.edu.\n\n\nReferences\n\nFlemmig TF: Periodontitis. Ann. Periodontol. 1999; 4(1): 32–37. 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(Northwood, London, England). 2011; 28(1): 121–126. PubMed Abstract | Publisher Full Text\n\nShen L, Du G: Lycium barbarum polysaccharide stimulates proliferation of MCF-7 cells by the ERK pathway. Life Sci. 2012; 91(9-10): 353–357. Publisher Full Text\n\nCheng J, Zhou ZW, Sheng HP, et al.: An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides. Drug Des. Devel. Ther. 2014; 9: 33–78. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJin M, Huang Q, Zhao K, et al.: Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L. Int. J. Biol. Macromol. 2013; 54: 16–23. PubMed Abstract | Publisher Full Text\n\nSangiovanni E, Fumagalli M, Dell’Agli M:Berries: Gastrointestinal Protection against Oxidative Stress and Inflammation.Gracia-Sancho J, Salvadó J, editors. Gastrointestinal Tissue. Academic Press;2017; 243–258. Chapter 18. 9780128053775. Publisher Full Text\n\nKwok SS, Bu Y, Lo AC, et al.: A Systematic Review of Potential Therapeutic Use of Lycium Barbarum Polysaccharides in Disease. Biomed. Res. Int. 2019; 2019: 4615718–4615745. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTian X, Liang T, Liu Y, et al.: Extraction, Structural Characterization, and Biological Functions of Lycium Barbarum Polysaccharides: A Review. Biomolecules. 2019 Aug 21; 9(9): 389. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPires TC, Dias MI, Barros L, et al.: Phenolic compounds profile, nutritional compounds and bioactive properties of Lycium barbarum L.: A comparative study with stems and fruits. Ind. Crop. Prod. 2018; 122: 574–581. Publisher Full Text\n\nSoesanto S, Jaya Soen RC, Oktaviani R, et al.: Goji Berry Extract (Lycium barbarum L.). Efficacy on Oral Pathogen Biofilms. 2021 IEEE International Conference on Health, Instrumentation & Measurement, and Natural Sciences (InHeNce). 2021; pp. 1–6. Publisher Full Text\n\nSchulz KF, Altman DG, Moher D, et al.: CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann. Intern. Med. 2010; 152(11): 726–732. PubMed Abstract | Publisher Full Text\n\nSanghavi AS, Chopra C, Ashmeet S, et al.: Evaluation of the antimicrobial, anti-adhesion, anti-biofilm and cell proliferation assay of a de-novo goji berry extract against periodontal pathogens: a comparative in-vitro study. J. Complement. Altern. Med. 2022. Publisher Full Text\n\nNavazesh M, Christensen CM: A comparison of whole mouth resting and stimulated salivary measurement procedures. J. Dent. Res. 1982; 61(10): 1158–1162. PubMed Abstract | Publisher Full Text\n\nFiguero E, Roldán S, Serrano J, et al.: Efficacy of adjunctive therapies in patients with gingival inflammation: A systematic review and meta-analysis. J. Clin. Periodontol. 2020 Jul; 47: 125–143.\n\nBrignardello-Petersen R: No benefits important to patients from the use of chlorhexidine rinse as an adjunct to scaling and root planing in patients with chronic periodontitis. J. Am. Dent. Assoc. 2017; 148(11): e172. PubMed Abstract | Publisher Full Text\n\nCieplik F, Jakubovics NS, Buchalla W, et al.: Resistance toward chlorhexidine in oral bacteria–is there cause for concern? Front. Microbiol. 2019 Mar 22; 10: 587. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhatia M, Urolagin SS, Pentyala KB, et al.: Novel therapeutic approach for the treatment of periodontitis by curcumin. J. Clin. Diagn. Res. 2014; 8(12): ZC65–ZC69. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBondia-Pons I, Savolainen O, Törrönen R, et al.: Metabolic profiling of Goji berry extracts for discrimination of geographical origin by non-targeted liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Food Res. Int. 2014; 63: 132–138. Publisher Full Text\n\nFiguero E, Nóbrega DF, García-Gargallo M, et al.: Mechanical and chemical plaque control in the simultaneous management of gingivitis and caries: a systematic review. J. Clin. Periodontol. 2017; 44: S116–S134. PubMed Abstract | Publisher Full Text\n\nForino M, Tartaglione L, Dell'Aversano C, et al.: NMR-based identification of the phenolic profile of fruits of Lycium barbarum (goji berries). Isolation and structural determination of a novel N-feruloyl tyramine dimer as the most abundant antioxidant polyphenol of goji berries. Food Chem. 2016; 194: 1254–1259. PubMed Abstract | Publisher Full Text\n\nChen J, Long L, Jiang Q, et al.: Effects of dietary supplementation of Lycium barbarum polysaccharides on growth performance, immune status, antioxidant capacity and selected microbial populations of weaned piglets. J. Anim. Physiol. Anim. Nutr. 2020; 104(4): 1106–1115. PubMed Abstract | Publisher Full Text\n\nFernández-Rojas B, Gutiérrez-Venegas G: Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects. Life Sci. 2018; 209: 435–454. PubMed Abstract | Publisher Full Text\n\nGan L, Zhang SH, Liu Q, et al.: A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells. Eur. J. Pharmacol. 2003; 471(3): 217–222. PubMed Abstract | Publisher Full Text\n\nBo R, Liu Z, Zhang J, et al.: Mechanism of Lycium barbarum polysaccharides liposomes on activating murine dendritic cells. Carbohydr. Polym. 2019; 205: 540–549. PubMed Abstract | Publisher Full Text\n\nShi H, Dong L, Jiang J, et al.: Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology. 2013; 303: 107–114. PubMed Abstract | Publisher Full Text\n\nHwang SJ, Kim YW, Park Y, et al.: Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm. Res. 2014; 63(1): 81–90. PubMed Abstract | Publisher Full Text\n\nChopra A: Goji berry mouthwash as alternative to chlorhexidine for managing chronic periodontitis. figshare. Figure. 2022. Publisher Full Text\n\nChopra A:Data on study titled: Lycium barbarum (Goji berry) mouthwash is a viable alternative to 0.2% chlorhexidine gluconate for managing chronic periodontitis: a randomized clinical trial. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "173857",
"date": "06 Jun 2023",
"name": "Rajinder K. Sharma",
"expertise": [
"Reviewer Expertise Periodontitis",
"periodontal medicine"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract: In abstract, results have been mentioned as significant in both the groups, however the p values mentioned don't corroborate the significant results. Please do the necessary corrections.\nIntroduction: It needs to be brief & relevant. The objectives of the study may be omitted in the introduction.\nMethodology Please describe in detail the method of randomization of 57 participants in test group(30) and control group(27).\nWere the participants recruited on consecutive order or in pooled manner?\nOut of 30 participants in test group, 15 were dropped out, only 15 were included in statistical analysis. Sample size calculation was 27 patients in each group. Rationale of sample size calculation is not served in this study. 'Around' 60 participants were recruited; Please avoid vague terms like 'around'. Please mention 57.\nOut of 27 allocated to control group, 16 were lost to follow up hence only 11 are left for follow up completion, however in the flow chart it is mentioned, 14 participants were analyzed. Please look into it.\nResults In the result section, demographic data is with reference to patients recruited whereas all other data is with reference to patients who completed the study. Similar data may be included in the result section, either all of the patients recruited or only the patients who have completed the follow up.\nAll the results have been presented in overall average values. PPD is an important parameter influencing the outcomes of periodontal intervention. Data needs to be segregated as per PPD.\nDiscussion: Please focus the discussion on the results of the overall study period of one month, unless there is some interesting finding otherwise.\nIt takes 6-8 weeks for healing to complete after SRP, Results of SRP are required to be estimated after this period. However the follow up of study period was one month; Please comment on it.\nA significant part of discussion is only review of literature with reference to Guji berry; Please avoid it as much as possible. Comment on the findings of your study may be the focus of discussion .\nConclusion: Conclusions are not based on the results of the study. For example \"L.barbarum is a promising superfood with many potential health benefits\", is not the conclusion of the study.\nL. barbarum has been investigated as an adjunct to SRP. Negative control is missing in the study. Hence the results can't be attributed exclusively to L.barbarum.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10528",
"date": "16 Nov 2023",
"name": "Aditi Chopra",
"role": "Author Response",
"response": "Firstly, we would like to thank all the reviewers and the editor for spending their valuable time and providing us with their valuable comments and suggestions. We truly appreciate your guidance in improving our work. We have tried to address the comments and revised the manuscript accordingly. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Reviewer 1 Abstract: In the abstract, results have been mentioned as significant in both the groups, however the p values mentioned don't corroborate the significant results. Please do the necessary corrections. Response: We thank the reviewers for their valuable insight. We have now revised the abstract and interpretation of the results. Introduction: It needs to be brief & relevant. The objectives of the study may be omitted in the introduction. Response: We thank the reviewer for their suggestion. We have now revised and shortened the introduction/background section in the abstract. Methodology: Please describe in detail the method of randomization of 57 participants in test group(30) and control group(27). Were the participants recruited on consecutive order or in pooled manner? Response: We have now added the method of randomization (computer-generated random sequence) in the abstract. The participants were recruited in as when they come to the OPD and randomized once the consequent order. Out of 30 participants in test group, 15 were dropped out, only 15 were included in the statistical analysis. The sample size calculation was 27 patients in each group. The rationale of sample size calculation is not served in this study. 'Around' 60 participants were recruited; Please avoid vague terms like 'around'. Please mention 57. Response: We thank the reviewer for their valuable suggestion. We have now revised paper accordingly and removed the word around along number of participants Out of 27 allocated to control group, 16 were lost to follow up hence only 11 are left for follow up completion, however in the flow chart it is mentioned, 14 participants were analyzed. Please look into it. Response: We thank the reviewer for their valuable suggestion. We have now revised paper accordingly and provided the corrected CONSORT flow diagram Results In the result section, demographic data is with reference to patients recruited whereas all other data is with reference to patients who completed the study. Similar data may be included in the result section, either all of the patients recruited or only the patients who have completed the follow up. Response: We thank the reviewer for their valuable suggestion. We have now revised paper accordingly and included the data related to the patients who were recruited All the results have been presented in overall average values. PPD is an important parameter influencing the outcomes of periodontal intervention. Data needs to be segregated as per PPD. Response: We thank the reviewers for their valuable insight. However, since it study was conducted on a small number of participant where segregation of PPD was not possible due to similarity in the amount of PPD, we have mentioned the data as combine reduction in PPD from baseline, moreover with segregation we found that all the patient fall under 1-3 mm of PPD and CAL loss due to recession of 1-2 mm . Discussion: Please focus the discussion on the results of the overall study period of one month, unless there is some interesting finding otherwise. It takes 6-8 weeks for healing to complete after SRP, Results of SRP are required to be estimated after this period. However, the follow-up of study period was one month; Please comment on it. Response: We thank the reviewer for the critical appraisal of these key findings. We have now added these points to the limitations of the study. We have kept the follow-up at 1 month as long-term use of chlorhexidine mouthwash is not recommended owing to the development of various side effects A significant part of discussion is only review of literature with reference to Goji berry; Please avoid it as much as possible. Comment on the findings of your study may be the focus of discussion. Response: We thank the reviewers for their valuable insight. We have now revised the manuscript accordingly. We have shortened the evidence on goji berry and discussed the clinical implications of our results and limitations of the study Conclusion: Conclusions are not based on the results of the study. For example \"L.barbarum is a promising superfood with many potential health benefits\", is not the conclusion of the study. Response: We thank the reviewers for their valuable insight. We have revised the conlucsion and removed the line suggested above. L. barbarum has been investigated as an adjunct to SRP. Negative control is missing in the study. Hence the results can't be attributed exclusively to L.barbarum. Response: We thank the reviewers for their valuable insight and agree with fact that the results are due to the combined effects of SRP with goji berry mouthwash. Since SRP is primary and the fundamental step that should be performed and matched in both the group we aimed to compared goji berry mouthwash with chlorhexidine. We have added these points to our discussion as you have suggested."
}
]
},
{
"id": "205506",
"date": "09 Oct 2023",
"name": "Francisco Wilker Mustafa Gomes Muniz",
"expertise": [
"Reviewer Expertise Periodontology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is the first round of peer review of this referee. Several queries were raised as stated below:\nOverall\nA very short follow-up period was followed for the chosen outcomes, such as BOP, CAL and PPD. A longer follow-up period, to detect any important change, is necessary. The antiplaque and antigingivitis efficacy may be important to the literature, though.\n\nThroughout the manuscript the term “periodontal disease” is used, maybe, referring to periodontitis. The term periodontal disease is very broad, and do not mean only periodontitis. Authors must revise it.\nTitle\nChlorhexidine is an excellent mouthwash to control biofilm and gingival inflammation. However, literature does not state that this mouthwash is useful for the treatment of periodontitis. Other treatments are more efficacious for this periodontal disease. Therefore, title must be revised, as it may be misleading in its current format. Please see Sanz, M., Herrera, D., Kebschull, M., Chapple, I., Jepsen, S., Berglundh, T., ... & Wennström, J. (2020). Treatment of stage I–III periodontitis—The EFP S3 level clinical practice guideline. Journal of clinical periodontology, 47, 4-60.\n\nMoreover, the term “chronic periodontitis” should not be used since 2018. Please see Caton, J. G., Armitage, G., Berglundh, T., Chapple, I. L., Jepsen, S., Kornman, K. S., ... & Tonetti, M. S. (2018). A new classification scheme for periodontal and peri‐implant diseases and conditions–Introduction and key changes from the 1999 classification. Journal of periodontology, 89, S1-S8. Prefer the term “periodontitis” whenever appropriate, and this must be applied to all manuscript.\n\nAdditionally, lower gain of CAL was detected in the test group. Title must not state that similar results were detected between groups.\nAbstract\nAuthors wrote: “A statistically significant difference was noted in the Pi (P-value = 0.791), Gi (P-value= 0.594), PPD (with P-value= 0.134), and microbial levels (P-value = 0.188) in both groups from the baseline.” However, none of the showed p-values mean statistical significance. The sentence is not understandable. Does the comparison mean within or between comparisons?\n\nConclusion may also be misleading. L. barbarum mouthwash presented similar clinical efficacy, when compared to chlorhexidine. The SRP performed may be the main reason to the so-called “effective in managing periodontal disease”. Please provide a interpretation aligned with your aims.\nIntroduction\nThe term “exaggerate” in the first paragraph should be revised, as may be not be the most appropriate term in an epidemiological point of view. In addition, authors have cited both risk factors and indicator factors associated with periodontitis.\n\nReference is necessary for the following sentence: “However, mechanical debridement is technically demanding, as many times removal of hard and soft tissue deposits from pockets greater than five mm becomes challenging.” In well-trained clinicians, this may not be a problem.\n\nProvide citation for the following sentences:\n“Recently, goji berry, commonly known as Wolfberry, Himalayan goji, or Tibetan goji, has gained a lot of popularity due to its strong antioxidant and anti-inflammatory properties.”\n\n“The stems and berries of goji berry plant was effective against many various Gram-negative bacteria and Gram-positive bacteria.”\n\nItalicize the word “in vitro.”\n\nReference #47 may not be necessary in the following sentence: “(…) efficacy of L. barbarum mouthwash along with SRP for patients with chronic periodontitis compared to chlorhexidine for the first time.47”\n\nWhy salivary levels of protein thiol were assessed in the present study? What is the relevance for the present study. This is not properly explained in this section.\nObjective\nPi, Gi, BOP, PPD, and CAL must be explained, as this is the first time their appear in the text.\nMethods\nFigure 1 do not represent the flowchart of the study, and do not follow what CONSORT recommends. Figure 1 is illustrative and important, but the sentence must be revised.\n\nFigure 2, in fact, must be placed in the Results section, as recommended by CONSORT.\n\nDo not use Stage 1, use “stage I.” Provide reference for this inclusion criterion\n\nDo not mistake exclusion criteria as the opposite of inclusion criteria. For instance, if only generalized periodontitis was included. It is not necessary to exclude those with localized periodontitis.\n\nWhat is “chlorhexidineg”?\n\nRevise the following sentence: “Participants currently using anti-inflammatory, antibiotics, or analgesics in the last six months.” It seems that patients that used antibiotics in the last six months were included.\n\nRevise exclusion criteria #10, as the sentence is in the future.\n\nSample size calculation is not properly described. Readers to not know the necessary number of patients to detect important measures in the primary outcome. For instance, the effect size of 0.7 is referring to what outcome?\n\nWhy allocation stated uneven (30:27) at baseline (Figure 2), as a 1:1 allocation ratio was established in the Methods?\n\nIn fact, allocation concealment is not properly explained.\n\nBoth mouthwashes may be very distinct in the general characteristics, such as taste, color and visual aspects. Therefore, this referee does not understand the following sentence: “The participants were also blinded about their group.”\n\nIt is well-established that the best periodontal examination must be performed in six sites per tooth. It is not clear why authors have performed it only in four.\n\nFurther information regarding chlorhexidine is necessary. Was it manufactured by the authors? What percentage was used? Provide details.\n\nChlorhexidine, such as those commercially available, must not be diluted in water. The lower efficacy of chlorhexidine must not be ruled out in the present study.\n\nIt is not clear for how long (who many seconds) volunteers should rinse.\n\nCalibration, if any, is not reported.\nResults\n\nIn Table 3, why p-values for the comparison between groups are reported only for baseline?\n\nThe following sentence should be better placed in the Methods: “(…) repeated measures of ANOVA with Greenhouse Geisser correction’ followed by a ‘post-hoc analysis with Bonferroni adjustment’.”\n\nFigure 3 and Table 3 are repetitive results. Both of them are not necessary.\n\nAuthors wrote: “One patient reported bitter taste of the mouthwash and discontinued the mouthwash.” What mouthwash?\nDiscussion\nEffectiveness was not tested. Do not mistake it with efficacy.\n\nOnly mild periodontitis patients were included in the present study. Do not generalize it. This type of patient is not discussed.\n\nThe following sentences are not correct: “Based on the results, it was noted that goji berry mouthwash can control the gingival inflammation, BOP, and plaque formation at 15 days following SRP with statistically significant difference compared to chlorhexidine group. A significant in the Gi, Pi, BOP, PPD was noted in participants using goji berry mouthwash.” No differences between groups were detected.\n\nAgain, chlorhexidine is not largely used for the management of periodontitis. In fact, its use as adjuvant to periodontitis treatment is not well-established, and the previously mentioned clinical practice guideline do not recommend it.\n\nA broader discussion regarding the L. barbarum on periodontal tissues is warranted.\n\nThere is no discussion regarding the very short follow-up period.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "10519",
"date": "16 Nov 2023",
"name": "Aditi Chopra",
"role": "Author Response",
"response": "Firstly, we would like to thank all the reviewers and the editor for spending their valuable time and providing us with their valuable comments and suggestions. We truly appreciate your guidance in improving our work. We have tried to address the comments and revised the manuscript accordingly. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Reviewer 2 A very short follow-up period was followed for the chosen outcomes, such as BOP, CAL, and PPD. A longer follow-up period, to detect any important change is necessary. The antiplaque and antigingivitis efficacy may be important to the literature, though. Throughout the manuscript the term “periodontal disease” is used, maybe, referring to periodontitis. The term periodontal disease is very broad, and do not mean only periodontitis. The authors must revise it. Response: We thank the reviewers for their valuable insight. We agree with the reviewer that a long-term follow-up is necessary, however, due to various side effects of chlorhexidine it is not advised to use for a long time. Additionally, there are studies that have found the development of antimicrobial resistance in periodontal pathogens against Chlorhexidine, hence the use of herbal mouthwashes is constantly being researched. We have also revised the term periodontal disease to periodontitis as suggested. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Chlorhexidine is an excellent mouthwash to control biofilm and gingival inflammation. However, literature does not state that this mouthwash is useful for the treatment of periodontitis. Other treatments are more efficacious for this periodontal disease. Therefore, title must be revised, as it may be misleading in its current format. Please see Sanz, M., Herrera, D., Kebschull, M., Chapple, I., Jepsen, S., Berglundh, T., ... & Wennström, J. (2020). Treatment of stage I–III periodontitis—The EFP S3 level clinical practice guideline. Journal of Clinical Periodontology, 47, 4-60. Moreover, the term “chronic periodontitis” should not be used since 2018. Please see Caton, J. G., Armitage, G., Berglundh, T., Chapple, I. L., Jepsen, S., Kornman, K. S., ... & Tonetti, M. S. (2018). A new classification scheme for periodontal and peri‐implant diseases and conditions–Introduction and key changes from the 1999 classification. Journal of periodontology, 89, S1-S8. Prefer the term “periodontitis” whenever appropriate, and this must be applied to all manuscript. Response: we thank the reviewers for sharing the article. Based on your suggestion we have now revised the title as follows: Efficacy of Lycium barbarum (Goji berry) mouthwash for managing periodontitis: a randomized clinical trial. We have now revised the terminology chronic periodontitis to periodontitis as requested. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Additionally, lower gain of CAL was detected in the test group. Title must not state that similar results were detected between groups. Response: we have now revised the interpretation as requested both in abstract and result/ discussion section. Abstract Authors wrote: “A statistically significant difference was noted in the Pi (P-value = 0.791), Gi (P-value= 0.594), PPD (with P-value= 0.134), and microbial levels (P-value = 0.188) in both groups from the baseline.” However, none of the showed p-values mean statistical significance. The sentence is not understandable. Does the comparison mean within or between comparisons? Response: we have now revised the result section and removed the following as they were baseline comparisons: that “statistically significant difference was noted in the Pi (P-value = 0.791), Gi (P-value= 0.594), PPD (with P-value= 0.134), and microbial levels (P-value = 0.188) in both groups.” Instead, we have now added the follow-up comparisons. The p-values are for intergroup comparison. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Conclusion may also be misleading. L. barbarum mouthwash presented similar clinical efficacy, when compared to chlorhexidine. The SRP performed may be the main reason to the so-called “effective in managing periodontal disease”. Please provide a interpretation aligned with your aims. Response: We thank the reviewers for their valuable suggestions. We have now revised the conclusion as follows: Goji berry mouthwash along with SRP was effective in reducing the Gi, Pi, BOP, and PPD. Goji berry mouth also increased the antioxidant levels in saliva in patients with periodontitis. Thus, goji berry mouthwash is a viable adjunct to SRP for patients with periodontitis. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Introduction The term “exaggerate” in the first paragraph should be revised, as may be not be the most appropriate term in an epidemiological point of view. In addition, authors have cited both risk factors and indicator factors associated with periodontitis. Response: We thank the reviewers for their valuable suggestions. We have now revised the term as follows: Apart from the microbial etiology, other risk factors that influence the severity of periodontal inflammation include smoking, diabetes mellitus, HIV, nutritional deficiency, medications, poor oral hygiene, and genetics. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Reference is necessary for the following sentence: “However, mechanical debridement is technically demanding, as many times removal of hard and soft tissue deposits from pockets greater than five mm becomes challenging.” In well-trained clinicians, this may not be a problem. Response: We have now added two references for this sentence as requested. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Heitz-Mayfield L.J., Trombelli L., Heitz F., Needleman I., Moles D. A systematic review of the effect of surgical debridement vs. non-surgical debridement for the treatment of chronic periodontitis. J. Clin. Periodontol. 2002;29((Suppl. S3)):92–102. doi: 10.1034/j.1600-051X.29.s3.5.x. Sherman P.R., Hutchens L.H., Jr., Jewson L.G., Moriarty J.M., Greco G.W., McFall W.T., Jr. The effectiveness of subgingival scaling and root planing. I. Clinical detection of residual calculus. J. Periodontal. 1990;61:3–8. doi: 10.1902/jop.1990.61.1.3. Provide citation for the following sentences: “Recently, goji berry, commonly known as Wolfberry, Himalayan goji, or Tibetan goji, has gained a lot of popularity due to its strong antioxidant and anti-inflammatory properties.” And “The stems and berries of goji berry plant was effective against many various Gram-negative bacteria and Gram-positive bacteria.” Response: We thank the reviewer for their suggestion, We have now added reference no 38-48 , which discusses the antimicrobial and antioxidant properties of the goji berry as suggested. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Italicize the word “in vitro.” Response: We thank you for your suggestion, We have now Italicized the word as requested. Reference #47 may not be necessary in the following sentence: “(…) efficacy of L. barbarum mouthwash along with SRP for patients with chronic periodontitis compared to chlorhexidine for the first time.47” Response: We have removed reference no 47 from the sentences mentioned above.- Why salivary levels of protein thiol were assessed in the present study? What is the relevance of the present study? This is not properly explained in this section. Response: we thank the reviewers for their valuable insight and key appraisal. we have now added the importance of assessment of local antioxidant levels in oral cavity as immune defense mechanisms in the discussion and introduction section. Since protein thiol is an important antioxidant during periodontal disease and the ability of goji berry to increase it levels in saliva as additional advantage over chlorhexidine. The changes in the manuscript have been highlighted in track change mode in the revised manuscript. Objective: Pi, Gi, BOP, PPD, and CAL must be explained, as this is the first time they appear in the text. Response: We have now added the full forms for each of the abbreviations in the objective section as suggested. Methods: Figure 1 does not represent the flowchart of the study, and does not follow what CONSORT recommends. Figure 1 is illustrative and important, but the sentence must be revised. Response: We thank the reviewers for the recommendation, we have now revised the figure 1. Figure 2, in fact, must be placed in the Results section, as recommended by CONSORT. Response: We thank the reviewer for their suggestion, we have now placed figure 2 in the result section. Do not use Stage 1, use “stage I.” Provide reference for this inclusion criterion Response: We have now revised the term Stage 1 to Stage I as suggested. Do not mistake exclusion criteria as the opposite of inclusion criteria. For instance, if only generalized periodontitis was included. It is not necessary to exclude those with localized periodontitis. Response: We thank the reviewer for their valuable insight. We have now revised the criteria as suggested : Participants in age group of 20-50 years diagnosed with stage I to stage II localized/generalized periodontitis (Grades A to B). What is “chlorhexidineg”? Response: We apologise for the Typo error, we have now corrected it as Chlorhexidine Revise the following sentence: “Participants currently using anti-inflammatory, antibiotics, or analgesics in the last six months.” It seems that patients that used antibiotics in the last six months were included. Response: We have now revised the sentence as follows: Participants who were on any anti-inflammatory, antibiotics, or analgesics in last six months were excluded Revise exclusion criteria #10, as the sentence is in the future. Response: We have now revised the sentence as follows: Participants using any other oral hygiene agents (mouthwash or gels) were excluded to remove confounding bias arising due to the difference in plaque control measures Sample size calculation is not properly described. Readers to not know the necessary number of patients to detect important measures in the primary outcome. For instance, the effect size of 0.7 is referring to what outcome? Response: We thank the reviewer for pointing our mistake and not mentioning the effect size linked outcome. The effect size was calculated based on clinical attachment loss. Why allocation stated uneven (30:27) at baseline (Figure 2), as a 1:1 allocation ratio was established in the Methods? Response: We thank the reviewer for their insight. We apologize for the mistake in numbers mentioned in the concealment. Allocation was done at ratio of 1:1 as mentioned in the method. We have now corrected and uploaded the revised figure as suggested. In fact, allocation concealment is not properly explained. Response: We thank the reviewer for their insight. We have now added an explanation on how the allocation concealment was done using opaque amber-colored bottles to mask the color of the mouthwash. Both types of mouthwash may be very distinct in general characteristics, such as taste, color, and visual aspects. Therefore, this referee does not understand the following sentence: “The participants were also blinded about their group.” Response: We agree with the reviewer that both goji berry and chlorhexidine mouthwash, mouthwash were stored in similar amber-colored bottles to mask the color of the mouthwash. However, differences in the taste will remain as a major factor in patient blinding/ concealment It is well-established that the best periodontal examination must be performed in six sites per tooth. It is not clear why authors have performed it only in four. Response: We agree with the reviewers and apologize for the ambiguity in the sentence we have performed periodontal examination on buccal, lingual, mesial, and distal (in the interdental area the probing was done both from the buccal and lingual side of the interdental area. We have now revised the sentence in the manuscript. Further information regarding chlorhexidine is necessary. Was it manufactured by the authors? What percentage was used? Provide details. Response: We have added the percentage of chlorhexidine (0.2%) Chlorhexidine, such as those commercially available, must not be diluted in water. The lower efficacy of chlorhexidine must not be ruled out in the present study. Response: We agree with the reviewers. however, the chlorhexidine used our study 0.2% was prepared and was diluted in 10 ml of water. It is not clear for how long (who many seconds) volunteers should rinse. Response: We have now added the time the mouthwash should be used in manuscript. Calibration, if any, is not reported. Response: Since single trained investigator examined the baseline and follow-up visits, calibration was not done. Results In Table 3, why p-values for the comparison between groups are reported only for baseline? Response: The p-values for comparison between groups at follow-ups and mentioned in the last columns of the same table. The following sentence should be better placed in the Methods: “(…) repeated measures of ANOVA with Greenhouse Geisser correction’ followed by a ‘post-hoc analysis with Bonferroni adjustment’.” Response: We have now revised the statement and mentioned it in Methods section. Figure 3 and Table 3 are repetitive results. Both of them are not necessary. Response: We agree with reviewer suggestions. We have now removed the figure 3. Authors wrote: “One patient reported bitter taste of the mouthwash and discontinued the mouthwash.” What mouthwash? Response: we have now added which group (Test group) patient reported bitterness. Discussion: Effectiveness was not tested. Do not mistake it with efficacy. Response: We have modified the title according to the suggestion and instead of effectiveness mentioned it as efficacy Only mild periodontitis patients were included in the present study. Do not generalize it. This type of patient is not discussed. Response: We have added this in the limitations this points our results The following sentences are not correct: “Based on the results, it was noted that goji berry mouthwash can control the gingival inflammation, BOP, and plaque formation at 15 days following SRP with statistically significant difference compared to chlorhexidine group. A significant in the Gi, Pi, BOP, PPD was noted in participants using goji berry mouthwash.” No differences between groups were detected. Response: We agree with the reviewers, we apologize for the error and interpreatation. we have now corrected the results section accordingly. Again, chlorhexidine is not largely used for the management of periodontitis. In fact, its use as adjuvant to periodontitis treatment is not well-established, and the previously mentioned clinical practice guideline do not recommend it. Response: we thank the reviewers for their recommendation, we have now added these points to our introduction and discussion sections A broader discussion regarding the L. barbarum on periodontal tissues is warranted. Response: We thank the reviewers for their recommendation. We have now added the role of the L. barbarum on periodontal pathogens, periodontal ligament fibroblast, neutrophils and wound healing References: Gan L, Zhang SH, Liu Q, et al.: A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells. Eur. J. Pharmacol. 2003;471(3):217–222. 12826241 10.1016/s0014-2999(03)01827-2 Bo R, Liu Z, Zhang J, et al.: Mechanism of Lycium barbarum polysaccharides liposomes on activating murine dendritic cells. Carbohydr. Polym. 2019;205:540–549. 30446138 10.1016/j.carbpol.2018.10.057 Du X, Wang J, Niu X, Smith D, Wu D, Meydani SN. Dietary wolfberry supplementation enhances the protective effect of flu vaccine against influenza challenges in aged mice. J Nutr 2014;144: 224–9.35. Ren Z, Na L, Xu Y, Rozati M, Wang J, Xu J, et al. Dietary supplementation with lacto-wolfberry enhances the immune response and reduces pathogenesis to influenza infection in mice. J Nutr 2012;142:1596–602. There is no discussion regarding the very short follow-up period. Response: We agree with the reviewer and we have added these points as the limitations of the study"
}
]
}
] | 1
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https://f1000research.com/articles/12-302
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https://f1000research.com/articles/13-1429/v1
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26 Nov 24
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{
"type": "Opinion Article",
"title": "Foundational Competencies and Responsibilities of a Research Software Engineer",
"authors": [
"Florian Goth",
"Renato Alves",
"Matthias Braun",
"Leyla Jael Castro",
"Gerasimos Chourdakis",
"Simon Christ",
"Jeremy Cohen",
"Stephan Druskat",
"Fredo Erxleben",
"Jean-Noël Grad",
"Magnus Hagdorn",
"Toby Hodges",
"Guido Juckeland",
"Dominic Kempf",
"Anna-Lena Lamprecht",
"Jan Linxweiler",
"Frank Löffler",
"Michele Martone",
"Moritz Schwarzmeier",
"Heidi Seibold",
"Jan Philipp Thiele",
"Harald von Waldow",
"Samantha Wittke",
"Renato Alves",
"Matthias Braun",
"Leyla Jael Castro",
"Gerasimos Chourdakis",
"Simon Christ",
"Jeremy Cohen",
"Stephan Druskat",
"Fredo Erxleben",
"Jean-Noël Grad",
"Magnus Hagdorn",
"Toby Hodges",
"Guido Juckeland",
"Dominic Kempf",
"Anna-Lena Lamprecht",
"Jan Linxweiler",
"Frank Löffler",
"Michele Martone",
"Moritz Schwarzmeier",
"Heidi Seibold",
"Jan Philipp Thiele",
"Harald von Waldow",
"Samantha Wittke"
],
"abstract": "The term Research Software Engineer, or RSE, emerged a little over 10 years ago as a way to represent individuals working in the research community but focusing on software development. The term has been widely adopted and there are a number of high-level definitions of what an RSE is. However, the roles of RSEs vary depending on the institutional context they work in. At one end of the spectrum, RSE roles may look similar to a traditional research role. At the other extreme, they resemble that of a software engineer in industry. Most RSE roles inhabit the space between these two extremes. Therefore, providing a straightforward, comprehensive definition of what an RSE does and what experience, skills and competencies are required to become one is challenging. In this community paper we define the broad notion of what an RSE is, explore the different types of work they undertake, and define a list of foundational competencies as well as values that outline the general profile of an RSE. Further research and training can build upon this foundation of skills and focus on various aspects in greater detail. We expect that graduates and practitioners will have a larger and more diverse set of skills than outlined here. On this basis, we elaborate on the progression of these skills along different dimensions. We look at specific types of RSE roles, propose recommendations for organisations, give examples of future specialisations, and detail how existing curricula fit into this framework.",
"keywords": [
"research software engineering",
"RSE",
"competencies",
"curriculum design",
"teaching"
],
"content": "Contents\n\n1. Introduction 3\n\n1.1 Terminology 4\n\n1.1.1 The term Research Software Engineer 4\n\n1.1.2 Further definitions 4\n\n2. Related work 4\n\n3. Values 5\n\n3.1 Current challenges 6\n\n3.1.1 Handling of data and personal data 6\n\n3.1.2 Mentoring and diversity 6\n\n3.1.3 Shaping digital science 7\n\n3.1.4 Addressing environmental sustainability within planetary limits 7\n\n3.1.5 Emerging challenges 7\n\n4. Foundational RSE competencies 7\n\n4.1 Software/Technical skills 8\n\n4.1.1 Classical software engineering skills 8\n\n4.1.2 Adapting to the software life cycle ( SWLC) 8\n\n4.1.3 Creating documented code building blocks ( DOCBB) 8\n\n4.1.4 Building distributable software ( DIST) 9\n\n4.1.5 Use software repositories ( SWREPOS) 9\n\n4.1.6 Software behaviour awareness and analysis ( MOD) 9\n\n4.2 Research skills 9\n\n4.2.1 Conducting and leading research ( NEW) 9\n\n4.2.2 Understanding the research cycle ( RC) 9\n\n4.2.3 Software re-use ( SRU) 9\n\n4.2.4 Software publication and citation ( SP) 10\n\n4.2.5 Using domain repositories/directories ( DOMREP) 10\n\n4.3 Communication skills 10\n\n4.3.1 Working in a team ( TEAM) 10\n\n4.3.2 Teaching ( TEACH) 10\n\n4.3.3 Project management ( PM) 11\n\n4.3.4 Interaction with users and other stakeholders ( USERS) 11\n\n4.4 RSE tasks and responsibilities 11\n\n5. How much do different people need to know? 12\n\n5.1 Career level 12\n\n5.2 Helpful RSE skills for researchers in an academic career 16\n\n5.3 Project team structures 17\n\n6. RSE specialisations 21\n\n6.1 Specialisations within the core RSE competencies 21\n\n6.2 Specialisations outside the core RSE competencies 21\n\n7. Future work 23\n\n8. Conclusion 23\n\nContribution details 24\n\nAcknowledgements 24\n\nReferences 28\n\nGlossary 32\n\nSkill codes 33\n\nAcronyms 33\n\n\n1. Introduction\n\nComputers and software have played a key role in the research life cycle for many decades. They are now vital elements of the research process across almost all domains. They enable researchers to collect and process ever-increasing amounts of data, simulate a wide range of physical phenomena across previously unexplored scales of the universe, and discover previously inconceivably complex structures in nature and societies via machine learning (ML). This prevalence of computation and digitally-aided data analysis in research means that digital skills are now required by researchers at all career levels, and in fields significantly beyond those that would previously have been expected. Research software is now used and developed not only in science, technology, engineering and mathematics (STEM) domains, but also in other fields, like medicine and the humanities.\n\nResearchers often lack the skills to use specialised software for their research, let alone write it.95 If they come from a non-technical domain, they may also struggle to know what to ask when trying to request help from and interact with more experienced colleagues. A gap still exists in academic education, as many curricula do not sufficiently prepare students in this regard. This situation is exemplified by the extracurricular Massachusetts Institute of Technology (MIT) class “The Missing Semester of Your CS Education”,85 which aims to increase “computing ecosystem literacy” even among students of Computer Science at MIT.\n\nResearchers investing increasing amounts of their time developing their software engineering (SE) skills to support their research work can find themselves with little time to do the research itself. This, in turn, presents career development challenges since the experience required to gain and progress in research and academic roles is traditionally assessed through metrics that do not directly include software outputs. A recent shift towards the establishment of the distinct role of a “Research Software Engineer”61 (RSE, a term that was coined in the United Kingdom (UK) a little over 10 years ago38), now provides a base on which sustainable career opportunities can be (and are being) built, allowing for better training of researchers and more effective support for the development of high quality research software. There is still a long way to go, but positive change is well underway.\n\nRSEs may work within one of the increasing number of research software engineering teams that have been set up at universities and research organisations over the past decade, or they may be embedded within a research team. They may have a job title that officially recognises them as an RSE, or they may have a standard research or technical job title such as Research Assistant, Research Fellow, or Software Engineer. Regardless of their job title, RSEs share a set of core skills that are required to design and develop research software, understand the research environment, and ensure that they produce sustainable, maintainable code that supports reproducible research outputs, following the Findability, Accessibility, Interoperability and Reusability (FAIR) principles.4\n\nThis community paper defines a set of core values and foundational competencies, which an RSE should acquire during training and formal education. These skills are formulated independently of a specific research domain and current technical tools used to support the application of the skills. By defining these competencies, we provide a guiding framework to facilitate the training and continuous professional development of RSEs, thus helping to provide a positive impact on research outputs and, ultimately, society as a whole. These competencies draw upon skills from traditional SE practice, established research culture, and the commitment to being part of a team. However, we see this set of skills as a foundation to build upon. We envision that through specialised training, the set of skills of graduate RSEs and domain researchers will grow. This is underlined by a growing interest to perform RSE research, i.e. research into methods and tools more catered to the unique challenges that research software provides.\n\nWhile this community paper is based on workshop discussions that were attended largely by RSEs (deRSE23 in Paderborn, un-deRSE23 in Jena, and deRSE24 in Würzburg, all in Germany), we believe that the competencies formulated here can offer far-reaching impact beyond the domain of RSE into adjacent aspects of research and, indeed, the wider research community. This is especially important given that much research involves some amount of data management, processing and visualisation, or the creation of tools for these tasks, and funding bodies and computing infrastructure providers will sometimes prioritise projects that generate archived, annotated, re-usable, and potentially remotely executable data. In particular, funding agencies and research managers will find the discussion in this paper valuable in order to discover where RSEs see their place in the existing landscape of scientific domains and how to support the work of RSEs at different positions and career levels.\n\nThe outline of the paper is as follows. We start with a non-exhaustive overview of existing initiatives in Section 2. Section 3 elaborates on the values that provide the guiding principles for the work of an RSE. Section 4 defines a set of core skills based on these values. We categorise these skills into three pillars, namely “software/technical”, “research”, and “communication” skills, reflecting the hybrid nature of an RSE. To justify the selection of these skills, we also list some current tasks and discuss the skills used therein. As with any general skill set, not all RSEs will need to use all the skills highlighted to the same level of expertise. Therefore, Section 5 examines how much a person needs to know depending on their education or career level or on the type of projects they would like to be involved with. In the same section, we provide an overview of what skills and limitations an RSE in different team structures typically has, and we give recommendations for organisations that need to support RSEs. Section 6 provides a list of RSE specialisations and discusses the level of skill needed to work in each of them, before we conclude the paper with details of future work in Section 7 and conclusions in Section 8.\n\n1.1.1 The term Research Software Engineer\n\nResearch Software Engineering can be considered an interface discipline, linking traditional Software Engineering with Research itself.51 Due to this nature there is a plethora of different variations of RSE depending on the particular Research domain they are working in. Therefore the broad notion of Research Software Engineers is better thought of as a collection of sub-communities. The term Research Software Engineer is made more difficult to grasp since an internationally recognised definition is still missing. While there is consensus about the general notion that an RSE is a person with one leg in their research domain and the other in software development, this spans a whole spectrum depending on which one is more emphasised. There is also the question of what level of professionalism concerning both non-SE research and SE is expected. A more inclusive definition allows more people to self-identify as RSEs, thereby also fostering an inclusive community of people working in digital science (see also Section 3 on the values of an RSE). RSEs fall therefore somewhere on the spectrum between a researcher at one end and a software engineer at the other. Common to all of them is, that they need to be able to work in the research environment the software is used in, ideally at eye-level with native researchers, but at least as close as possible. RSEs often need to deal with non-technical complexities that are characteristic for research environments: organisational, motivational, with respect to the size of projects, independence and heterogeneous goals of stakeholders, boundary conditions for funding and future funding, to name just a few. Summarising, RSEs have skills and experience in three important areas: in the research area(s) their software is used in, in software engineering topics, as well as in interdisciplinary communication.\n\n1.1.2 Further definitions\n\nDepending on the national research environments and processes that readers are familiar with, the notion of the terms software and research might differ. Therefore, to avoid ambiguities, we define these as follows:\n\nSoftware: Source code, documentation, tests, executables and all other artefacts that are created during the development process that are necessary to understand its purpose.\n\nResearch software: Foundational algorithms, the software itself, as well as scripts and computational workflows that were created during the research process or for a research purpose, across all domains of research. This definition is broader than in4 and is the outcome of a recent discussion in.35\n\nResearch software engineers: People who create or improve research software and/or the structures that the software interacts with in the computational environment of a research domain. They are highly skilled team members who may also choose to conduct their own research as part of their role. However, we also recognise that many RSEs have chosen specifically to focus on a technical role as an alternative to a traditional research role because they enjoy and wish to focus on the development of research software.\n\nResearchers: People who are using the services provided by Research Software Engineers. This, on purpose, is a very broad definition and was chosen for a better reading.\n\n\n2. Related work\n\nVarious initiatives are working to support technical professionals develop their computational skills. Particularly related to this work are initiatives that aim to define sets of such skills and to guide the community with certification programs and training resources.\n\nRSE Competencies Toolkit: The RSE Competencies Toolkit70 is a community project that developed out of a hack day activity at the 2023 edition of the annual Software Sustainability Institute Collaborations Workshop.14 The toolkit provides a web application that aims to support technical professionals in understanding how to develop their skills. It enables them to build a profile of their competencies within the system, while it also provides a set of training resources that are linked to a competency framework.\n\nHPC Certification Forum: The High-Performance Computing (HPC) Certification Forum84 is working towards providing a certification process for HPC skills. As part of this process, the group is developing a Competence Standard83 and an associated skill tree that provides a classification of HPC competencies. This work aims to develop a standardised representation of relevant HPC knowledge and skills which can, in turn, lead to structured and recognised sets of skills that can underpin the certification process.\n\nEMBL-EBI Competency Hub: The European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI) Competency Hub20 provides a bioinformatics/computational biology-focused example of a competency portal. In addition to collecting information on a range of competencies that can be browsed within the web-based tool, it also provides career profiles for roles within the domains that EMBL-EBI focuses on. The hub provides access to a variety of training resources that are linked to the specific competencies that they relate to. This enables learners to more easily find the right training materials in order to support their career development journey, helping them to identify what they might want to learn and in what order.\n\nTraining-focused initiatives: Further initiatives implicitly define sets of competencies by providing (open) teaching material for selected skills. This is a non-exhaustive list of related initiatives, which will be discussed in more detail in a separate publication. In some cases, the activities extend beyond training, but they do not focus on defining frameworks of competencies.\n\nOne prominent example is the Carpentries,81 a non-profit entity that supports a range of open source training materials and international communities of volunteer instructors and helpers who run courses around these materials. A similar framework is provided by CodeRefinery,13 currently funded by the Nordic e-Infrastructure, as well as SURESOFT,79,7 a project at Technical University (TU) Braunschweig and Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, funded by the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) and targeting more advanced SE topics such as software design principles, design patterns, refactoring, continuous integration (CI) and test-driven development (TDD).\n\nThere are also several initiatives focused on training HPC-oriented RSEs, such as the Partnership for Advanced Computing in Europe (PRACE)65 (with material aggregated on various websites, e.g., on EuroCC Training21), Understanding and Nurturing an Integrated Vision for Education in RSE and HPC (UNIVERSE-HPC)90 (a project funded under the UK’s ExCALIBUR research programme25), and the EuroCC National Competence Center Sweden (ENCCS),23 which offers a collection of lessons for HPC skills.22\n\nInitiatives focused on Germany include EduTrain62 (a section of the National Research Data Infrastructure (Nationale Forschungsdateninfrastruktur) (NFDI)30), the Helmholtz Federated IT Services (HIFIS),36 and the already mentioned SURESOFT.79\n\n\n3. Values\n\nIt is important that the activities of an RSE are guided by ethical values. In addition to the values for good scientific practice,27 RSEs also adhere to the SE Code of Ethics.33 Central to that code is the RSE’s obligation to In addition to the values for good scientific practice commit to the health, safety and welfare of the public and act in the interest of society, their employer and their clients. Further values loosely based on that code include the obligations\n\n• to commit to objectivity and fact-based, honest research conclusions,\n\n• to promote openness and accountability in the research process,\n\n• to take great care to develop software that adheres to current best practices,\n\n• to judge independently and maintain professional integrity,\n\n• to treat colleagues and collaborators with respect and work towards a fair and inclusive environment, and\n\n• to promote these values whenever possible and make sure that they are passed on to new practitioners.\n\nThe deployment of computer-based modelling and simulation has dramatically changed the practice of science in a large number of fields. It has enabled the hitherto impossible study of new classes of problems, often replacing traditional experimentation and observation. It can also serve to integrate a communal body of knowledge.64 Humphreys41 regards this development as “more important than the invention of the calculus in the 1660s, an event that remained unparalleled for almost 300 years”. The epistemological status of computer modelling and simulation is still the subject of debate, which ranges from the postulate of a new process of knowledge creation that has its own, unique, epistemology97 to the perception that from a philosophy of science perspective, there is nothing really new.28 In any case, it is clear that a number of decisions in the construction of a simulation-model will have a significant impact on the adequacy for purpose8 of the model. These decisions include the selection of the salient characteristics of the system to be modelled, the choice of the mathematical representation of the processes to be represented, the choice of numerical methods and other algorithms and even including the design of the user-interface.\n\nThe relationship between initial state, inputs and final state of a computer simulation is “epistemically opaque”,41 in that not every step of the process is directly observable. The current trend of an increasing application of computationally irreducible systems, such as those based on artificial neural networks, further exacerbates this inherent limitation of explainability. An RSE usually takes a pivotal role in assessing this adequacy for purpose of a model as well as in characterising and communicating the domain of its legitimate application and its limits of interpretability. This role, together with the enormous reliance on modelling and simulation of scientific results, as well as real-world decision-making, places a large responsibility on the RSE. It is important that RSEs are aware of this responsibility and continuously improve their capabilities to live up to it.\n\nResearch software is also well on its way to being ever-present in data-driven research, in all research fields. This can probably be most prominently seen by considering software used to analyse data, e.g. within experimental research. It is not unusual for RSEs to support those more research data oriented efforts as well. Here, specifically, they closely interact with research data management professionals and practices by designing research software that is better able to adhere to the FAIR principles for research data, but also to follow similar rules for research software (FAIR4RS4). As such, they are then familiar with special requirements stemming from the field itself, e.g., in medical research, and with privacy related issues especially for personal data, e.g., for conducting surveys.\n\nRSEs often assume a multifaceted role at the junction of research, SE and data management. They work with a varying and diverse set of colleagues that might include other developers, support unit staff and academics of different fields and all career stages. This situation yields a specific set of challenges RSEs should be aware of to consciously make ethically sound judgement calls. We list some example areas that highlight present-day challenges.\n\n3.1.1 Handling of data and personal data\n\nA lot of RSE work involves the manipulation or creation of data processing tools. We highlight that professional conduct requires these creations to be reliable and to maintain data integrity. In particular, the way that personal data is handled can have far-reaching implications for society. Independent of the encoding into the respective national law in an RSE’s jurisdiction, the right to information privacy is internationally recognised as a fundamental human right, e.g., in the European Convention on Human Rights.15,40 RSEs need to be aware of this topic’s importance and deal with tensions that might arise with researchers’ desire for trouble-free sharing of data, thereby expecting openness about the research process, versus the integrity expectations of the society towards information technology (IT) systems. Handling personal data also has ramifications for information security considerations during the software development process. Data protection is a complex topic, so RSEs should be aware that they may need to consult external expertise, for example when dealing with special topics such as cryptography or re-identification attacks.37\n\n3.1.2 Mentoring and diversity\n\nRSEs are often experienced professionals who work closely with and provide technical training and guidance to early career researchers. Similarly to academic supervisors, they bear a certain responsibility to guide and advise less-experienced colleagues with respect to career development and the achievement of academic goals. This can take the form of supervising a student or mentoring a fellow RSE. The RSE needs to be aware of the biases arising from the sociological imbalances in research and academia. According to the United Nations Educational, Scientific and Cultural Organization (UNESCO) Science Report72 women account for 33.3% of all researchers. 60.2% of researchers come from high-income countries which account for 17.5% of the global population in 2018. Furthermore, the socioeconomic background of academics is not representative of the general population, for example in the US a tenure-track academic is 25 times more likely to have a parent with a PhD.59 Thereby, to promote their values of an honest, open, and inclusive research space, they should be aware of the diversity problems and help to mitigate them whenever they have the chance to do so.\n\n3.1.3 Shaping digital science\n\nThrough writing research software, RSEs have a pivotal position in the process of scientific production. Their choices might determine whether the respective research is reproducible or not, whether the results can be re-used, whether future research can build on existing tools or has to start from scratch. Builders of larger research-infrastructure projects determine to some extent the possibilities and limitations of future research and therefore need to be able to make a value-based judgement on topics such as open science, path dependence, and vendor lock-in.\n\n3.1.4 Addressing environmental sustainability within planetary limits\n\nThe last two decades saw transistor technology approach the limits of attainable miniaturisation, and maximum chip clock frequency begin to plateau.80 Nevertheless, a misleading belief in limitless growth of computing capabilities (storage, computing power, transfer speed) is still widespread within popular perception. A practical consequence of this is an ever-growing demand for resources to cover the expanding need of storage and processing, with no clear deceleration in sight (e.g. the IEA estimates a doubling in data centres energy consumption from 2024 to 202642). At the same time, current science is well aware of several planetary boundaries being exceeded due to human activities.69 Data processing, storage and transfer account for a non-negligible fraction.42 Demands to move resource consumption to a sustainable rate are well justified and supported by science.75\n\nRSEs have the opportunity to contribute to this effort by, for example, choosing computationally adequate approaches (e.g. recognising where a proven statistical method may suffice in place of a power-hungry AI model, or configuring a test pipeline to minimise redundancy), and embracing data frugality measures (e.g. recognising sufficient resolution when sampling data for processing or storage). If past computational solutions were frugal because of technological limits, in future they should tend to that by virtue of an awareness of what may be adequate. The Governance, Responsibility, Estimation, Energy and embodied impacts, New collaborations, Education and Research (GREENER) principles54 suggest how these concerns can be addressed and how research computing can become more environmentally sustainable.\n\n3.1.5 Emerging challenges\n\nRSEs often operate at the cutting edge of technological development and therefore might have to deal with technologies of which the dangers and drawbacks are still poorly understood. A current example is the rush for the application of large language models (LLMs), where RSEs working in these fields should stay up-to-date and be able to help researchers assess topics such as training-data bias, LLM “hallucinations” or malicious use, with the greater goal of making these powerful tools work for the welfare of society.\n\n\n4. Foundational RSE competencies\n\nThe role of an RSE lies somewhere on the spectrum between that of a researcher (the “R”) and a software engineer (the “SE”) and, therefore, requires competencies in both fields. RSEs typically have a background in research or software engineering, but they definitely have obtained broader knowledge in both fields. Even when working as the only RSE on a task or project, they typically apply their knowledge and experience as part of larger teams of researchers and technical professionals, which allows them to cultivate this hybrid nature. There are many ways to categorise the competencies of an RSE. We chose to distribute these competencies over three pillars to reflect the fact that RSEs are both competent researchers (the research skills, Section 4.2) and software engineers (the software/technical skills, Section 4.1). The third pillar (communication skills, Section 4.3) forms the bridge between the former two categories, with a particular focus on the software and research cycle and the scientific process. These competencies are relevant in a broad setting and form the foundation for specific specialisations. These competencies have been chosen in order to make RSEs contribute to an open and inclusive research environment, with tools that respect their professional values.\n\nThese skills and competencies come into play in various forms: The RSEs themselves need to acquire and develop them as their career progresses (Career level). However, some knowledge of software and data processing is required at all academic levels and for all positions (Academic Progression). The relative importance of the skills and competencies also depends on the size of the RSE team (Project team size). Finally, different sets of skills are emphasised in the different RSE specialisations (RSE specialisations).\n\nDuring the Paderborn workshop (deRSE23) we asked learners and novice RSEs what they would like to have learnt. The top five items mentioned were: testing, contributing to large projects, when or why to keep repositories private, high-quality software development, and finding a community. Those topics comprise combinations of the skills and competencies defined below. We will elaborate these in Section 4.4.\n\nBesides skilled researchers, RSEs are also competent software engineers. As such, they ideally can solve complex software engineering problems and design software as a user-oriented, future-proof product. The technical skills required by an RSE overlap to a large extent with the common fundamental software engineering skills (see, e.g., Landwehr et al.52), but put greater emphasis on aspects related to achieving good scientific practice and to serving special needs of research software. In addition, a lot of RSEs are either self- or peer taught in these skills (see, e.g., figure 14 in Barker et al.5). These skills include requirements analysis, design, construction, testing, program analysis, and maintenance of software. On the other hand, RSEs also know how to make research software adhere to the FAIR principles,4 and how to achieve different levels of research software reusability (see, e.g., Chue Hong12), while they have deeper understanding of the scientific context around the research software projects they work on. To reflect this, the technical skills listed below complement competencies regarding the standard life cycle of software development (as summarised in subsubsection 4.1.1) with RSE-specific focus skills.\n\n4.1.1 Classical software engineering skills\n\nTo summarise the vast range of the skills a software engineer is typically equipped with, we refer to the Guide to the Software Engineering Body of Knowledge (Bourque, Fairley, and IEEE Computer Society9). Because research software engineering is an interface discipline, RSEs are often stronger in topics more commonly encountered in research software contexts (e.g., mathematical and engineering foundations) than in other areas (e.g., software engineering economics). However, they bring a solid level of competence in all software engineering topics. Therefore, RSEs can set and analyse software requirements in the context of open-ended, question-driven research. They can design software so that it can sustainably grow, often in an environment of rapid turnover of contributors. They are competent in implementing solutions themselves in a wide range of technologies fit for different scientific applications. They can formulate and implement various types of tests, they can independently maintain software and automate operations of the integration and release process. They can provide working, scalable, and future-proof solutions in a professional context and with common project and software management techniques, adapted to the needs of the research environment. Finally, as people who have often gained significant research experience in a particular discipline, they combine the necessary foundations from their domain with software engineering skills to develop complex software.\n\n4.1.2 Adapting to the software life cycle ( SWLC)\n\nThe traditional software development life cycle defines the stages that form the process of building a piece of software. Initial development generally involves an analytic process where requirements and ideas are gathered and analysed (requirements engineering), followed by formulating a plan to fulfil them (design) that is finally turned into running code (implementation). This is accompanied by different measures of quality control (e.g., reviews, testing), validating and verifying that things work as expected and that they continue to do so when development progresses further. Depending on the software project, this can mean a simple “Think-before-you-do”, or more elaborate and formal processes. Often the development cycles are executed iteratively and incrementally. The life cycle further includes periods of deployment, maintenance and further development (software evolution), as well as software retirement. To assess the current state and needs of the software, the RSE should be familiar with different maturity metrics, e.g. the DLR application classes,71 the research software maturity model16 or technology readiness levels (TRLs). Additionally, the research software life cycle extends the traditional life cycle with software publication. The RSE should be aware of this life cycle and be able to predict and cater to the changing needs of a software project as it moves through the stages.\n\n4.1.3 Creating documented code building blocks ( DOCBB)\n\nThe RSE should be able to create building blocks from source code that are reusable. This ranges from simple libraries of functions up to complex architectures consisting of multiple software packages. An important part of enabling code reusability is the provision of sufficient information in the form of comments within code, documentation or other means. This is vital to ensure that developers and maintainers understand what a piece of software aims to do and how to enable others to use the provided functionality. This is primarily achieved through a “clean” implementation and enhanced by documentation. Documentation ranges from commenting code blocks to using documentation (building) tools. It should be written with consideration for the different audiences who may need it depending on their goals and expertise, for example by following the Diátaxis framework.66\n\n4.1.4 Building distributable software ( DIST)\n\nThe RSE should be able to distribute their code on their domain/language specific distribution platforms. This almost always encompasses handling/documenting dependencies with other packages/libraries. It sometimes requires knowledge of using build or package management systems to enable interoperability with other projects. In terms of usability and needs of the user community the RSE should be able to decide whether a library or a framework is the right type of program to build and distribute.\n\n4.1.5 Use software repositories ( SWREPOS)\n\nThe RSE should be able to identify and use fitting public platforms (so-called software repositories or “repos”) to share the artefacts they have created and invite the public to scrutinise them in public reviews. These software repositories usually provide facilities for software development, which differentiate them from the domain repositories described later.\n\n4.1.6 Software behaviour awareness and analysis ( MOD)\n\nWe define this as a certain quality of analytical thinking that enables an RSE to form a mental model of a piece of software in a specific environment (program comprehension). Using that, an RSE should be able to make predictions about a software’s behaviour. This is a required skill for common tasks such as debugging, profiling, optimising, designing good tests, or predicting user interaction. Many tools exist to help with understanding and evaluating existing code, especially from a structural point of view. An RSE should understand their output and its implications. An important facet of this capability relates to information security. RSEs need to consider the safety and integrity of personal data and other sensitive information and make sure that they do not negatively impact the integrity of their institution’s network and computing infrastructure.\n\n4.2.1 Conducting and leading research ( NEW)\n\nRSEs are curious and able to conduct research, both on research software engineering, and on their research-wise “home domain” (see also section 5.4.1). Senior RSEs are also able to lead research, and many RSEs have a doctorate.39 Since RSEs often operate in different research fields, they also gain their reputation from their effectiveness in interacting with researchers from the same or other domains. Therefore, some curiosity together with a broad overview of the research field is required, as this enables the RSE to learn new methods and algorithms directly from domain peers. Similarly, a broad overview of the field of SE research and the growing field of RSE research enables the RSE to learn, apply, and teach new methods and tools for improving the way they develop software. This curiosity, together with the ability to convert it into new ideas, is also reflected when an RSE is actively trying out new tools or discovering related literature from adjacent domains. Lifelong learning is then no longer just a phrase but becomes a motivation to work.\n\n4.2.2 Understanding the research cycle ( RC)\n\nOne of the key skills that RSEs have is their understanding of how research works. They embrace being part of a larger community which, despite friendly competition, shares the common goal of gaining knowledge to disseminate it. Thereby they know that they are part of a bigger undertaking that involves many other parties in and outside their domain, and also that their software can be utilised at different stages of the research cycle by different people. They may be asked to contribute to the ethical and regulatory evaluation of a project to ensure integrity of the research performed therein. Like other researchers, RSEs are open to discussions and arguments beyond their own expertise and appreciate the underlying principles of good research, including publications, reviews and reproducibility.\n\n4.2.3 Software re-use ( SRU)\n\nThe re-use of existing assets such as libraries and pieces of code to improve efficiency and quality belongs to the fundamentals of software construction.9 To discover software, RSEs rely on domain-specific knowledge and domain repositories, as well as research skills, discovering related software via software citations and metadata. To evaluate whether the artefacts to be re-used suit their needs, RSEs often need to consider the scientific context of their origin. For example, a paper that references the code under consideration might be crucial to validate its fitness for purpose or lack of suitability. Code that incorporates research-domain specific knowledge needs to be understood at a very detailed level and its re-use documented to meet standards of good research practice. Not only the technical compatibility needs to be understood and documented (programming languages, system interoperability), but also the underlying models and computational methods need to fit the purpose; this question often requires wider research skills and deeper understanding of the research domain at hand.\n\n4.2.4 Software publication and citation ( SP)\n\nAnother part of FAIR software is concerned with publishing new and derived works and making them available for re-use by the research community and the general public. RSEs need to have a basic understanding of common software licence types, including proprietary and open source licences and how “copyleft” and “permissive” open source licences differ. They should also understand compatibility between different licences, and the ramifications for re-using and composing programs. Beyond that, RSEs will need to properly execute the technicalities of software publishing. These include the application of licences and copyright statements, understanding and assigning software authorship, crediting contributors, maintaining FAIR software metadata and publishing software artefacts. Finally, RSEs will need to understand the principles of software citation.76 This concerns both the potential for reuse of their own work, which demands the provision of complete and correct up-to-date citation metadata for their software, as well as their own citation obligations deriving from building on previous work in the form of dependencies.\n\n4.2.5 Using domain repositories/directories ( DOMREP)\n\nAlmost all research software is developed within a specific scientific domain. Some software may be able to cross boundaries, but the majority will have a home domain, with which it needs to be able to interact. The RSE then needs to be aware of any domain specific repositories that will contain data sets, catalogues, and other domain specific artefacts, in addition to software. The RSE also needs to be aware of how their software can interact with the existing domain-specific data repositories. Finally, they need to be able to assess and use software repositories - domain-specific or generic - for publishing software with the relevant metadata.\n\nRSEs do not work in isolation. They are embedded in a research group or work within a team of RSEs supporting particular research projects. RSEs often need to interact with and facilitate communication among colleagues, clients and contractors with a very broad spectrum of background-knowledge, specialisation, expectations, and experience whilst keeping diversity issues in mind (Section 3.1.2). Communication skills are therefore crucially important. Team skills are also mentioned in common guides for SE such as the software engineering body of knowledge.9 However, the interpersonal and organisational skills and the capacity for adaption required to work in a research setting warrants a much stronger emphasis on this field of competence.\n\n4.3.1 Working in a team ( TEAM)\n\nBeing able to work, and effectively communicate in teams is essential for RSEs. For example, RSEs need to be able to explain particular implementation choices made and may even need to defend them. Within a team of RSEs, code reviews improve knowledge transfer and increase team cohesion. The team might change on a project-to-project basis and might be comprised of colleagues with very different backgrounds including, for example, IT staff, domain scientists and technicians working alongside software engineers. The shared values come into play and each RSE needs to ensure that these values are lived by and passed on to others. Senior RSEs may lead a team of RSEs.\n\n4.3.2 Teaching ( TEACH)\n\nRSEs have many opportunities to teach. These range from inducting new colleagues to teaching digital skills either through short courses, for example from The Carpentries,81 or entire lecture series. RSEs may also act as mentors and consultants. Code review also includes aspects of the teaching skill.\n\n4.3.3 Project management ( PM)\n\nThe RSE should have knowledge of project management processes. At some institutes, project management tools and approaches differ between individual research groups, but it is useful if an RSE understands general structures of a PM scheme, or can bring in new ideas for improvement. Project management in research software engineering poses specific challenges (see USERS) that might require the capacity to flexibly adapt to changing conditions and deviate from common project management methods. Additionally, the RSE should know that SE offers various methods and approaches specifically tailored to management of software projects and products.\n\n4.3.4 Interaction with users and other stakeholders ( USERS)\n\nSince research software is often developed as part of the research process itself, its requirements and specifications might change with the progression of research. Stakeholders of research software often change across different research projects or even within the course of one project. Roles in connection with research software are often in flux and diffuse. For example, a single person might be user, developer and project manager at the same time. Often this means it is necessary for an RSE to think “outside their comfort zone”, but at the same time to be able to convey their knowledge and experience to experts of other fields or persons at different hierarchy levels in a way they can understand more easily. These conditions pose specific challenges for requirements analysis, project management, training and support.\n\nThese skills, while already numerous are also generic on purpose. They span a multidimensional space in which the day-to-day tasks and responsibilities of an RSE can be found. We describe here some examples of the competencies applied in combination to the set of current common tasks and challenges for RSEs identified during the deRSE23 Paderborn workshop.\n\nThe most obvious task of an RSE is to develop software that is used in research. This broad topic requires all the SE skills. Of course, these are the competencies that are the most fluid since they have to adapt to frequent technological advancements. Additionally, proper SE skills often require knowledge of TEAM, and PM. Today, this means effective use of integrated development environments (IDE), static analysis tools, design patterns and documentation (for oneself and others).\n\nThe RSE needs to be able to formulate and discuss structural and behavioural aspects of software on a more general level than through the code itself and often even before a first line of code is written. A set of tools and diagrams for effective and standardised communication about software on a meta level is provided by the Unified Modelling Languages (UMLs). As a modelling tool, it is directly related to MOD. Additionally, it can be applied in various stages of the SWLC, especially in the early stages, as a first documentation of the planned modular structure to facilitate DOCBB, USERS, PM and TEAM.\n\nThe RSE needs to be able to choose appropriate algorithms and techniques ( MOD and NEW). Apart from the technical feasibility, this choice is also informed by the values outlined in Section 3. For example, the RSE needs to be able to estimate resource usage (processing, memory and storage consumption, e.g.53). Resource usage has not only a direct financial price tag but also environmental costs via associated energy consumption.\n\nSoftware development also includes testing. This task is a manifestation of the SE competencies of DOCBB and MOD since a model of the software is required in order to write good tests that facilitate understanding and documentation. Today this encompasses the knowledge of testing frameworks as well as continuous integration and continuous delivery (CI/CD) practices. In addition to being tested, software should also provide reproducible outputs. Projects like ReproHack68 can greatly help in fostering that competency.\n\nApart from testing, there are many code analysis tools to monitor and improve the quality of code. An RSE should be familiar with the tools available for their specific environment and how to include some of them into a CI/CD pipeline. Typically, this includes linters and similar static tools as well as dynamic tools like profilers and code coverage analysis. The development of these tools is very dynamic and environment specific. A good introduction can be found in Ref. 9 and an online resource is.91 As these tools help with behavioural and structural analysis and therefore modularisation these tools enable MOD as well as DOCBB.\n\nPart of the FAIR principles is to make software findable and reusable. The RSE needs to be able to decide when and why to keep a repository private. This decision requires knowledge in RC, USERS, TEAM, and sometimes SP. Furthermore, knowledge of the practices and contractual regulations of the RSE’s institution is also required. The RSE also needs to understand metadata for research data and research software. There are ongoing efforts on metadata for research software such as CodeMeta45 and the National Research Data Infrastructure (NFDI, Nationale Forschungsdateninfrastruktur) working group11 on the subject. These are complemented by the development of new tools and methods for providing and working with software metadata, such as the Citation File Format project18 and HERMES.19 Other efforts focus on Software Management Plans (e.g., Refs. 1, 57) which could be helpful for RSEs at early stages (i.e., with not much experience of project management). They give quick hints on what to look for regarding basic management for research software (including information on, e.g., licenses, releases, publication, citation, archiving) together with some ongoing work on corresponding metadata.32 Metadata can also be used actively during and within a research project, to inform the decision-making processes.6\n\nMost RSEs will contribute to other projects, some of which will be large. This is a topic that requires competency in SWREPOS, SRU, and SP in order to understand the ramifications of sharing, and in DOCBB, since the contributed code has to be understood by others. Interacting with project members depends on the TEAM skill. Today, this frequently involves the effective use of collaborative platforms like GitHub/GitLab, honouring a project’s code of conduct, and some knowledge of popular open source software licences, e.g. the General Public License (GPL).\n\nRSEs are embedded in communities. There are two different aspects to finding these communities: First, we have the aspect of community building for a research project. Since this deals with software that is supposed to be used in research this requires knowledge of RC, USERS, and also NEW, in order to effectively interact with domain scientists. Today, an example is a presence on social media. The other TEAM-related aspect is the embedding of recently-trained RSEs into the Research Software Engineering community, sharing the same set of values and competencies. We envision newcomers to the RSE field becoming part of a strong network of RSEs, tool-related communities, and the classical domain communities, making them more effective at supporting research. These networks are a lifelong manifestation where RSEs work to provide an inclusive environment for their peers and provide opportunities for lifelong learning.\n\nRSEs are also mentoring colleagues (see also Section 3.1.2). This necessitates giving good advice that fits to a project’s stage in its life cycle, thereby requiring knowledge of ( SWLC), and its context in its research domain and thus ( RC). Research software can often start out as a tool to answer a personal research question, becoming more important when other researchers start to rely on it. At the other end of the scale, research software can sometimes underpin key processes that deal with critical questions such as weather forecasting or medical diagnosis. A classification of software is commonly used to formalise the process of giving good advice71,92 where research software can move from one class to another during its life cycle.71 classifies applications based on their scope and criticality and provides SE recommendations. The RSE needs to be able to identify the application class they are dealing with and apply the respective RSE practices.\n\nOften RSEs, especially in RSE groups, will develop applications and services with different variants for different research purposes and groups. Additionally, many research groups develop their own codes for specific research purposes, e.g. simulation codes or specialised data analysis pipelines. A lot of their development of new features is project-based, often through PhD projects. Work can sometimes result in code that diverges from the main project into a separate variant with re-integration planned as a final step. To reduce the chance of variant source code diverging significantly and producing a large integration overhead, PM skills and methods are needed. More specifically, software product line management methods have been developed for this exact problem and purpose.\n\n\n5. How much do different people need to know?\n\nNow that we have the different competencies, we can explore various dimensions of these competencies, depending on their circumstances. A strong beneficiary of specialised RSEs can also be newly formed RSE centres at research institutions.\n\nAt different career levels, differing skills are required. To elaborate on that, we have prepared the following table with three levels of experience in mind.\n\n• Junior RSE: These are people who are in the earlier stages of their RSE career journey, but they should ideally have research experience of their own as well as the skills to contribute reliable and well-structured code to software projects.\n\n• Senior RSE: They have gained experience, both concerning their software skills as well as in their research collaborations in potentially many different fields. They can set the standards in a software project.\n\n• Principal RSE: Their actual job description varies a lot. These may be RSE team leaders based in a professional services type role, or they may be professors or research group leaders based in a more academic-focused role. They are often the people responsible for bringing in the funding that supports new and sustains existing projects. Generally speaking, they do not need to be actively involved in the day-to-day technical tasks, but they should be able to guide projects from both a technical and a research perspective while providing an inclusive working space.\n\nTable 1, Table 2, and Table 3 elaborate on the required facets of the competencies in different roles. A story-like example of an individual through the hierarchies can be found in section 5.4.2.\n\nIn the previous section, we looked at the competency levels needed for RSE specialists. However, many of these competencies are important for researchers in academia as well. Naturally, the ‘R’ competencies apply, and research in general is increasingly team based. Additionally, many researchers in fields from classical examples like numerical mathematics or theoretical physics to newer disciplines like digital humanities will spend time in their research on writing and developing software. Therefore, RSE focused training, e.g., in a master’s programme, is also beneficial for students in these fields resulting in a broader audience. This also means that students as well as researchers need to be given time to acquire those skills, e.g., to be able to attend training in RSE-relevant topics as part of their regular work or study.\n\nThis section outlines how the RSE competencies could be reflected at all academic levels. It is important to note that this section does not reflect the current state of academic training and research institutions. Instead, it summarises the discussions with and between workshop participants at different levels of academic progression on what they would have liked to learn at an earlier stage or know before starting their current position. While individuals already work at implementing some of these changes and teaching these skills, it has not yet reached a systemic level.\n\nThe text is organised along the academic progression path (bachelor’s degree, master’s degree, PhD, Postdoc, Principal Investigator (PI)/Professor). Since each level is based on the previous levels, we presume that the skills and competencies at each level also encompass those of the previous levels. Due to the broad need throughout academic specialisations, the described levels serve as a baseline and certain fields will require higher SE skill levels as development is a large part of their actual research.\n\nBachelor’s level Students at the undergraduate level mostly consume science/knowledge. During their studies, they should also learn about the existence of digital tools and structures. Undergraduate students should be aware that RSEs exist and that software has different quality aspects ( DOCBB). They should be aware of domain specific tools ( DIST, SRU) and where to find them ( SWREPOS, DOMREP). At this level, it may be sufficient to consider software as black boxes ( USERS) although some training in data presentation would be very helpful and a good way to find out about programming ( MOD, NEW). They should have an awareness of software licences and whom to ask regarding licensing issues ( SP). They will be taught about the research cycle ( RC) and that researchers often work in groups ( TEAM). During practicals, they will have an opportunity for peer learning ( TEACH).\n\nMaster’s level A student at a master’s level can participate in science and should therefore be able to use “some” digital structures. A master’s student needs to be aware of relevant tools and data sets for their domain, where to find them and how to use them ( DIST, SWREPOS, DOMREP). They should be able to process and present their data ( MOD). They need to understand how their research depends on software ( SWLC). Working on their master’s thesis allows them to understand the research cycle ( RC), practice project management ( PM) and collaborate with other members of their research group ( TEAM).\n\nPhD PhD students perform independent research under guidance. They need to know relevant tools and structures. They should know where to find information about tools and where to find help using them ( DOCBB, SWREPOS). They should be able to use the tools ( DIST) and identify and report bugs ( MOD). They need to be aware that the user’s perspective is different from the developer’s perspective in order to be able to write good bug reports ( USERS). They might produce new software ( MOD, SRU), in which case they need to understand how to licence their code for publication ( SP). PhD students need to be curious to be able to conduct their research. In order to be able to explore new tools ( NEW) they must be able to evaluate research software ( SWLC). They need to be able to interact with services ( RC) and domain specific repositories ( DOMREP). They should be able to supervise a student ( TEACH).\n\nPostdoc Postdocs are independent researchers. Their role is similar to that of a PhD student, with a deepened focus on their research career. However, they are proficient users of all relevant tools, which makes them active contributors to their domain of research. They need to be aware of more advanced topics regarding intellectual property rights, such as patents ( SP).\n\nPI/Professor They are experts in their field and should be able to give proper guidance to their students on which digital tools are currently relevant. They should be aware of the skills of an RSE and when they might need one in their group. They should encourage their students to use relevant tools ( DIST). They need to be able to judge the suitability of the software ( SWLC) and follow the interactions between relevant projects ( SWREPOS). They should be able to advise their students on the legal aspects of software production and distribution ( SP). They should be able to contribute meaningfully to the steering decisions of the software in their field ( USERS). They are able to guide students and prepare and deliver a full lecture course ( TEACH). They need to manage and lead their research group ( PM, TEAM).\n\nIn Table 4, Table 5, and Table 6, we look at individual or team competencies and approaches to them, considering how these differ depending on whether an RSE is working alone on a software project, or whether they are working as part of a team of RSEs. We extend this to consider how things differ when an RSE or a group of RSEs is based locally within a research team or department, or when they are based in a dedicated, centralised RSE team. We also look at organisational aspects in the context of each of the considered competencies, since there are a variety of ways that organisations can contribute to and support them, complementing those proposed by Ref. 48. Some of them are brought to life in the example career path of section 5.4.1. We first summarise the meaning of each of the columns in the tables:\n\n• Competency: The code assigned to the competency being considered, as defined in Section 4, e.g. TEAM.\n\n• Individual RSE (Locally-based): A single person working on some research software - often an RSE with focus on their own research. Often time-constrained, may be self-taught.\n\n• Individual RSE (RSE team-based): A single person working on research software - generally a professional RSE assigned to support another team’s software on their own, who however is connected to an RSE team.\n\n• Group of RSEs (Locally-based): A group within a research group or team, working together on software to support or undertake a single research goal/project. Similarly to the individual RSE, they are often research-focused with RSE skills, often self-taught.\n\n• Group of RSEs (RSE team-based): An RSE team working together on research software projects for a research group.\n\n• Organisation-level RSE support: Describes how the defined competencies are recognised and represented at an organisational level and what the organisation can do to support the RSEs in the context of the different team structures. These can be read as policy/action recommendations.\n\nThese tables take the perspective of the expected skill set of each RSE or team of RSEs, similarly to personas in a user experience analysis. The current situation may differ.\n\nIn the tables above, we have looked at how different competencies can be related to and handled by researchers and RSEs working in different environments within an organisation and how the organisations themselves can contribute. We recognise that this is a challenging area to gain a detailed view of and that this is still a significant generalisation. We talk about the “Research Software Engineer” as a single entity but as the field expands, we expect to see more roles and job titles emerging around the RSE concept, many of which fit under the wider umbrella of research technology professionals (RTPs).44,87 Examples are different RSE-like computational roles of the EMBL-EBI BioExcel competency framework67 (also section 6.3.1), as is a range of different roles from King’s Digital Lab at King’s College London.77\n\n5.4.1 An example master’s programme for research software engineering\n\nThe target audience for such a master’s programme are students holding a bachelor’s degree from a domain science, which we will call “home domain” in the following. There is explicitly no restriction on the candidates’ home domain: it may be from the STEM disciplines, life sciences, humanities or social sciences, and it can also change later in their career. Candidates with a bachelor’s degree in computer science are also explicitly included, although we acknowledge that their master’s programme should include adaptations to make their interaction effective with other domain scientists. In order to give the future RSE the necessary breadth, we expect this to be a four-semester curriculum.\n\nThe curriculum is formed from a combination of modules, some of which are core modules teaching essential skills that must be completed by all students. Other modules introduce more specialised concepts and skills. During the master’s programme, students should pick an RSE specialisation from the list in this paper and attend these additional modules to deepen their knowledge in that field.\n\nCore modules are of course drawn from the three pillars of the RSE and can be categorised accordingly.\n\n• Software/Technical skills:\n\n– Foundational module: Here we have an introduction to programming: Emphasising use cases over programming paradigms, students learn at least two languages: a language that facilitates prototyping and data processing (e.g., Python or R) and a language for designing complex, performance-critical systems (e.g., C/C++). This exposes them to computers in a hands-on fashion and is the foundation for ( DOCBB, DIST).\n\n– Computing environment module: Programming languages are not enough to work in a landscape of many interconnected software components; hence we require something like software craftsmanship, where tools such as the Unix shell, version control systems, build systems, documentation generators, package distribution platforms, and software discovery systems are taught to strengthen skills in ( DIST, DOCBB, SWREPOS, SRU).\n\n– Software engineering module: Here we develop foundational software engineering competencies (basic knowledge and skill regarding requirements engineering, software architecture and design, implementation, quality assurance, software evolution), again emphasising and strengthening ( DOCBB, DIST) on a more abstract level.\n\n• Research skills:\n\n• Optional domain mastery module: Additional minor research courses, but students with a home-domain already have the research part well-covered. Courses here should be allowed to fall in any research field, and those outside of the own home-domain should be especially encouraged.\n\n• Research tools module: Here we teach tools used to distribute and publish software, as well as introducing students to domain specific data repositories, thereby gaining foundational knowledge in ( SRU, SP, DOMREP).\n\n• Meta-research module: Here we teach people how research works. The research life cycle is introduced, as well as the data life cycle and the software life cycle are abstractly introduced.\n\n• Communication skills:\n\n– Project management methods: Here we teach project management methods that are useful in science, such as agile ones ( PM).\n\n– Communication skills module: Here we have courses focusing on interdisciplinary communication, interacting across cultures, communication in hierarchies, supporting end users effectively. These are all facets of the ( USERS) skill.\n\n– Teaching module: This module covers topics to effectively design courses and teaching material for the various digital tools, thereby strengthening the ( TEACH) skill.\n\nGiven that RSE work also involves a lot of craftsmanship skills, hands-on practice is an integral part of the curriculum. At least two lab projects are required within the mandatory curriculum. These should be executed as a team and involve a question from a domain science. We recommend covering both the candidate’s home domain as well as a different one. Ideally, projects stem from collaborations with scientists within the institution and RSE students take the role of a consultant. This setup strengthens the ( TEAM, TEACH, USERS) skill and encourages also the ( MOD) skill through interaction.\n\nTo emphasise the exposure to domains outside their bachelor’s degree domain, we recommend that RSEs also support their non-home-domain project with introductory courses from this discipline. This schools their ability to quickly adapt their vocabulary and thinking to other disciplines and is an aspect of ( MOD).\n\nTo align with the specialisations listed in this paper, example optional modules include topics on HPC engineering/parallel programming, numerical mathematics/scientific computing, web technologies, data stewardship, AI models/statistics, and community management/training.\n\nThe programme is finalised with a master’s thesis which should be dual-supervised by an RSE supervisor from an actual project, and a domain supervisor. The thesis should answer a relevant research question from the domain using computational methods, strengthening ( NEW). Software development is required, and the code is part of the gradable deliverables. The RSE supervisor ensures and grades the software craftsmanship aspects of the project. This setup ensures that we are grading the effectiveness of applying RSE skills in an actual research environment.\n\n5.4.2 An example of a possible career path\n\nSetting the stage Meet Kay, Kim’s2 younger sister who currently studies researchology in a bachelor’s programme in the established domain of researchonomy at University of Orithena (UofO). We will follow Kay’s fictional career to illustrate how education, job-experience and a career in academic institutions could lead to become a successful RSE. In Kay’s world, some of the measures proposed in this paper have already been implemented.\n\nBachelor’s degree Through a program like Software Carpentry78 or The Missing Semester,3 Kay learns about using computational tools to support the sophisticated statistical analysis typical for researchology. She uses those tools to create and automate the steps of processing data and producing outcomes for her bachelor’s thesis (generating plots with matplotlib and even CI for automatic building) and takes pride in a fully open and reproducible bachelor’s thesis enabling her to graduate with honours from the faculty of researchonomy.\n\nMaster’s degree Kay ponders whether to continue with computational researchology, which her bachelor’s supervisor is responsible for, or enrol in a domain-agnostic RSE master’s programme. Researchers in computational researchology need to acquire a large part of the general RSE know-how presented in this paper and specialise in Quantum-Accelerated Bayesian Optimisation methods. However, Kay decides to go for the more generic route of a dedicated RSE programme because she wants to continue in academia, but does not like the idea of becoming stuck with one research topic. She also experienced the immediate satisfaction gained by helping colleagues from her research group with tricky technical problems, which makes her happier than the subdued sense of achievement from having a research paper accepted long after she had written it. For her, coding and sharing knowledge in the form of software is of similar importance to writing a paper focused mostly on the obtained results.\n\nThe domain-agnostic RSE Master programme consists of a core of RSE topics with various electives for specialisation, some of them domain-specific (e.g., chemistry) or topic-specific (e.g., cloud computing for research). Kay chooses digital archaeology and develops a pipeline for reconstructing 3D models from ground penetrating radar data, to simplify the process for archaeologists (reproducibility, big data, ML). The project management skills that are being taught as part of the core RSE curriculum really help her to not get lost in this project. Apart from working with the researchers in her archaeology group, she has to work with members of the central RSE department to help her with the pipelines. She also has to liaise with the central IT department to organise storage for the large data sets. Towards the end of the programme, she visits her first RSE conference where she sees a lot of notions ( SWLC, RC) in action that so far have been abstract in her master’s degree.\n\nThe exposure to the wider RSE community inspires her to invest additional time into her thesis to publish her software project under a licence approved by the Open Source Initiative and to write an accompanying article in the open source journal JOSS.47 Inspired by the discussion with reviewers of her JOSS paper, and the citation metadata file that JOSS created automatically for her when her paper is published, Kay starts to think more about making her software FAIR. She reads up on the topic in a guide suggested to her, the Turing Way,88 and creates metadata files that provide the citation metadata and general description for her software. She adds the files to her source code repository, and also adds an automated CI/continuous delivery (CD) pipeline that updates metadata and creates a new publication record in the Zenodo repository for each new release. Kay has now completed the RSE programme and has reached Junior RSE level.\n\nJunior RSE Kay finds a position in the central RSE department at her university with a competitive IT salary. Although the contract is temporary, there is a good chance that it will lead to a permanent position. The university makes an effort to enable that since it is a member of “The Technician Commitment”,87 an initiative to ensure recognition and career development of technicians, who face similar challenges to RSEs. Kay completes the Software Carpentry Instructor training and teaches basic research computing, while advising fellow students of her department on better programming ( DOCBB and MOD skill). She also runs a seminar in the RSE Master’s programme. She publishes a condensed version of that in JOSE.46 During her teaching duties, she becomes aware of a new project in her department that requires a community manager RSE, and she gladly signs up to focus more on her communication skills. After three years, she takes an exciting opportunity to work in another university.\n\nSenior RSE The new position involves taking responsibility for the RSE related aspects of a large inter-organisational project. With her new responsibilities comes a shift in the importance of various aspects of her work. Having this position in an inter-organisational project places far more emphasis on communication and organisation skills. She is spending time teaching people ( TEACH skill) to onboard them into the project. There is a lot of interaction with different stakeholders in the project like funders and user groups ( USERS skill). To oversee the project, she uses an amalgamation of both agile and traditional project-management concepts and methods which she acquires on-the-job ( PM skills). Her work so far has already been heavy on ( TEAM) skills, but now also the leadership aspect comes into play.\n\nRSE-focused principal investigator The job experience as a leading RSE for a large project was the last requirement necessary to be awarded the title of a “Certified Research Software Professional” (CRSP) from an institutionalised centre of RSE education. The certificate confirms her track record of valuable software contributions and of teaching and mentoring people, as well as her capability to enable, foster and contribute to high-quality research in a leading position. It is recognised by various funding agencies, such as the DFG, and hence enables RSEs to act as a PI for RSE-focused grant applications. It is also recognised by many prestigious universities and opens many career options that are also typical for PhDs. Kay can now write her own grant proposals to effectively fund work of moving research software projects from prototypes to infrastructure.\n\n\n6. RSE specialisations\n\nWhat we have defined above are intended to be base skills that an RSE irrespective of domain, position, and experience should know about. There is a large variety of RSEs. They specialise in different areas, some of which we want to present below. Many of the specialisations may overlap, so the same RSE might for example work on data management and open science. We categorise them into those that can be viewed as a specialisation within RSE-specific topics, while other RSEs might expand their skill set and profession to areas that are not typical for an RSE.\n\nOpen science RSE Open science and FAIRness of data and software are increasingly important topics in research, as exemplified by the demand of an increasing amount of research funding agencies requiring openness. Hence, an open science RSE is required to have a deeper knowledge of ( RC) and how to distribute software publicly ( SRU, SP). Open Science RSEs can help researchers navigate the technical questions that come up when practising Open Science, such as “How do I make my code presentable?”, “How do I make my code citable?”, “What do I need to do to make my software FAIR?”, or “How do I sustainably work with an (international) team on a large code base?”. Like the Data-focused RSE, they have a deep understanding of research data management (RDM) topics.\n\nProject/community manager RSEs When research software projects become larger, they need someone who manages processes and people. In practice, this concerns change management for code and documentation and community work to safeguard usability and adaptability, but also handling project governance and scalable decision-making processes. This gap can be filled by people who invest in the ( PM), ( USERS), and ( TEAM) skills, as exemplified in section 5.4.2. Building a community around a research project is an important building block for sustainable software,74 so these RSEs play an important role, even if they do not necessarily touch much of the code themselves.\n\nTeaching RSEs RSEs interested in developing their ( TEACH) skill can focus on teaching the next generation of researchers and/or RSEs and will play a vital role in improving the quality of research software. They need to have a good understanding of all RSE competencies relevant to their domain and additionally should have teaching experience and training in didactics and pedagogy.\n\nUser interface/user experience designers for research software Scientific software is a complex product that often needs to be refined in order to be usable even by other scientists. To facilitate this, there are people required that specialise in the ( DOCBB) and probably the ( DIST) competency with a focus on making end-user facing software really reusable and hence FAIR. This task is supported by strong ( MOD) skills to reason about the behaviour of potential users of the software.\n\n${DOMAIN}-RSE While software is the common focus of all RSEs, there will be RSEs that have additionally specialised in the intricacies of one particular research domain, such as medical RSEs, digital humanities RSEs, or physics RSEs. This can often serve as a base domain for RSE specialisation as in section 5.4.1.\n\nData-focused RSE Data-focused RSEs work at the flourishing intersection between data science and RSE. They are additionally skilled in cleaning data and/or running data analyses and can help researchers in setting up their analysis pipeline and/or RDM solutions. When the field requires research on sensitive data or information, e.g., patient information in medicine, this RSE should have knowledge about secure transfer methods and/or ways to anonymise the data. As part of RDM, this RSE profile is able to support all stages of the research data life cycle,63 with synchronous data management processes. Those processes implement established best practices for planning and documenting of data acquisition in a data management plan (DMP), as well as for management, storage, and preservation of data, and publication and sharing of data in repositories according to the FAIR principles.96\n\nResearch infrastructure RSE This RSE has a special interest in SysOps and system administration and sets up IT infrastructures for and with researchers. Therefore, this specialisation on the one hand requires a deep knowledge of physical computer and network hardware and on the other hand knowledge about setup and configuration of particular server software, e.g., setup of virtual machines on hypervisors or the planning and setup of compute server clusters for special purposes, e.g., ML. As an interface between the researchers and the infrastructure, they take care of user management, access permissions, and configuration of required services.\n\nHPC-RSE RSEs with a focus on HPC have specialist knowledge about programming models that can be used to efficiently undertake large-scale computations on parallel computing clusters. They may have knowledge of (automatic) code optimisation tools and methods and will understand how to write code that is optimised for different types of computing platforms, leveraging various efficiency related features of the target hardware. They are familiar with HPC-specific package managers and can build dependencies from sources. They also understand the process of interacting with job scheduling systems that are often used on HPC clusters to manage the queuing and running of computational tasks. HPC-focused RSEs may be involved with managing HPC infrastructure at the hardware or software level (or both) and understand how to calculate the environmental impact of large-scale computations. Their knowledge of how to run HPC jobs and write successful HPC access proposals can be vitally important to researchers wanting to make use of HPC infrastructure.\n\nML-RSE The development of research software based on ML requires additional specialised theoretical background and experienced handling of appropriate software in order to produce meaningful results. This involves knowledge about data analysis and feature engineering, metrics that are involved in ML, ML algorithm selection and cross validation, and knowledge in mathematical optimisation methods and statistics. Here, we use ML in a broad sense of machine-based learning including deep learning, reinforcement learning, neuro-symbolic learning and similar.\n\nML-RSEs analyse and check the suitability of an algorithm. They check if it fulfils the needs of a certain task and they play a central role in deciding on and selecting ML libraries for a given task. The increasing usage of ML in numerous scientific areas with social impact involves an emphasised awareness and consideration of possible influences and biases. At the intersection of data science29 and data-focused RSEs, the complex way of solving problems utilising ML calls for this separate specialisation.\n\nLegacy RSEs Research software may have evolved over generations of researchers without change management or governance processes, while software “ecosystems” (e.g., programming languages, frameworks, operating systems) constantly evolve. This may lead to the emergence of legacy code that is still actively used. To safeguard continued usability and adoption, these RSEs have experience in working with code written in language standards and on software stacks considered deprecated by their communities. Adaption of existing, large-scale codebases to evolving dependencies ( DIST) or changing hardware (HPC; see the HPC-RSE specialisation) may require mastery in refactoring techniques and in the usage of specialised code transformation tools.\n\nWeb-development RSE This RSE is skilled in the development of web applications and/or mobile apps. They have expertise in one or more of frontend development, backend development and the design or implementation of APIs, for example to support research data portals or big research projects. Since a lot of web services for research may be accessible to a large audience or even to the public, this RSE is also familiar with aspects relating to cybersecurity, usability and accessibility. Not only do they need to balance these concerns while adhering to their values from Section 3, but they also need to efficiently communicate the decisions made to stakeholders.\n\nLegal-RSE RSEs are often the go-to person for questions about software licensing, in particular when mixing software components that use different licences. But with the rising requirements from legislation, we foresee the need for RSEs that still have a background in RSE but extend it with a knowledge of legal processes that cover corner cases and go beyond applying Best Practice guides. These requirements may arise in the area of publication of research software, as this also requires knowledge about particular laws or regulatory frameworks concerning data protection, like the General Data Protection Regulation (GDPR) within the European Union (EU).82 Another area are legal aspects of cybersecurity and export control in science and research (see Ref. 26 for Germany). Legal-RSEs focus on facilitating the achievement of technically feasible solutions, while adhering to regulatory mandates. They are able to communicate and collaborate effectively with lawyers.\n\n6.3.1 Bioinformatics skills and certification\n\nBioinformatics is another field that actively works on developing skill trees. The Bioinformatics Core Competencies,60,93,94 the BioExcel competency framework,58 the PerMedCoE competency framework,56 the Research Data Management and Data Stewardship competence framework17 and the ELIXIR Data Stewardship Competency Framework for Life Sciences73 are examples of grassroots efforts aiming at defining the set of skills of various bioinformatics specialities, one of them as a taxonomy.60 These frameworks eventually converged into the EMBL-EBI Competency Hub,20,55 where typical RSE and bioinformatician profiles at different levels of seniority can be queried (e.g., Junior RSE, Senior Computational Chemist) and compared against one another (e.g., Junior vs. Senior RSE).\n\nCompetencies can be divided into more fine-grained building blocks: knowledge, skills and abilities (KSAs). They can be organised in a taxonomy, and are also transferable, i.e. a KSA can be a prerequisite to multiple competencies. The Mastery Rubric for Bioinformatics89 and the ELIXIR Data Stewardship Competency Framework for Life Sciences73 are examples of KSA frameworks for bioinformatics curricula.\n\nThe Curriculum Task Force of the International Society for Computational Biology (ISCB) curates a database of degrees and certificates in bioinformatics.43,60 The database includes bachelor’s and master’s degree programs and specialisations, PhD programs, and certificates from graduate schools.\n\nBioExcel has research competencies that combine some of our research competencies and some notions from the communication skills. Their computing competencies roughly map to our software skills. Here, we find competencies such as “package and distribute software”, which maps to our ( DIST) competencies, and “comply with licensing policy”, which would in our framework be part of ( SP) in the research competencies. In addition, they have a dedicated parallel computing competency section, thereby shifting the emphasis of the knowledge of their computational tools towards the HPC-RSE specialisation in our framework. Career profiles, such as the computational chemist, bring additional domain specific knowledge; we would classify those as a mixture of ${DOMAIN}-RSE and HPC-RSE. It is noteworthy, however, that the BioExcel framework puts very little emphasis on communication skills, which are often involved in RSE-related tasks.\n\n6.3.2 HPC skills and certification\n\nAs an area that generally requires a range of advanced skills, HPC is one field where there is ongoing work to identify relevant sets of skills for HPC practitioners and potential paths to develop these skills. The HPC Certification Forum83 has developed a competence standard for HPC that defines a range of skills and how they are related in the context of a skill tree.49,50 This competence standard is currently being built upon by the CASTIEL 224 project in collaboration with initiatives funded by the European High-Performance Computing Joint Undertaking (EuroHPC JU) to create a framework for HPC certification.34 While this framework focuses mostly on skills specific to HPC, there are a couple of similarities to the framework proposed in this paper. The “SD: Software Development” skill set is very similar to the SE skills discussed in Section 4, describing a wide range of such skills. This skill set contains Programming Best Practices (SD2), Software Configuration Management (SD3), Software Quality (SD5), Software Design and Software Architecture (SD6), and explicit mention of documentation (SD7, see our DOCBB). Besides the Software Concepts for HPC (SD1), which mainly concerns HPC-focused RSEs, most of the skills contained in the SD2-SD7 categories apply to all RSEs. A significant difference compared to the framework proposed in this paper is the absence of skills related to research or communication. Noteworthy is already now the level of detail in their skill tree which is more similar to section 5.4.1.\n\nAlso looking at pathways and how different skills are related, the UNIVERSE-HPC project,90 funded under the UK’s ExCALIBUR research programme,25 is looking to understand and develop training pathways to support the development of specialist skills in the HPC and exascale domains. The project is gathering open source training materials to develop curricula that support the training pathways that are underpinned by high-quality training materials.\n\n\n7. Future work\n\nThis list and description of competencies is a first step to finding common ground around which to structure curricula, institutions, and teachers in this framework. An omission that we found and that we would like to highlight in order to spark a community discussion is that RSEs that choose explicitly a science-supporting role outside of research will not be eligible for funding under the statutes of many funding organisations that require at least a PhD.\n\nTo alleviate this and to give RSEs in leadership positions a means to become eligible for funding themselves, since completion of scientific training is often a requirement,31 we see two possible parts of a solution. One is to allow for doctorates primarily based on software contributions to the scientific community. Secondly, we propose the introduction of new, standardised certificates like those of section 5.4.2, and to officially accept them as PhD-equivalent concerning eligibility to be a PI. Beyond this discussion, a diverse set of publications on the topic of RSE teaching is already in the making.\n\nWithin this set, we will work next on how to institutionalise education. In that publication, we will detail how we organise our institutions and what qualifications our teachers need to have in order to effectively communicate our values. We will put forward ideas on how to build up bachelor’s and master’s programmes, of which a glimpse can already be found in section 5.4.1. We will show how we intend to provide the necessary continuous education for RSEs after graduation, and we will connect that with the integration of RSEs into a mesh of community networks aimed at supporting research, while providing them with an inclusive social network that further facilitates lifelong learning. That publication will again intentionally be free of regional specifics, to also serve as a blueprint that other national RSE societies can build upon.\n\nOnline resources for courses are another important building block. This is the general intention of the learn-and-teach project.86 Surveying and curating of existing resources is not carried out as a traditional publication, but it is made available as a continuously-evolving online resource at.86\n\nAnd finally, we plan to formulate a call to action, building on the previously mentioned publication on the necessary institutions, that spells out everything that is required to best support the continuous need for young RSEs to support digital science specifically in Germany.\n\n\n8. Conclusion\n\nThis paper started from a community workshop at deRSE23 in Paderborn where people working in RSE related fields got together to figure out structures and ideas for educating newcomers to this field. One outcome of this diverse gathering is that RSEs from differing fields gather around similar core concepts, At the same time they share a vision of how to renew scientific research practice making extensive use of digital tools. In this publication, we have tried to formalise these concepts. We have formulated a set of values that guide our actions in society, manifestly making RSEs part of the scientific community that shares the ideals of good scientific practice. At the same time, being close to software engineers, we cherish that we have to take responsibility for our tools. We listed core competencies that have been intentionally formulated abstractly without referencing any particular information-processing device. As expected, we have drawn equally upon notions from SE and other research fields, but found that we likewise require teamwork capabilities. We detailed these competencies in various dimensions and found that a different amount is required in different positions and scientific domains. Using this, we proposed recommendations for organisations to foster the development of these competencies.\n\nThe gathered values and competencies form a common denominator that unifies RSEs and enables them to identify with this domain, in the knowledge that it is already or will soon become critically important for many areas of science. These competencies at the intersection of research and SE, coupled with a firm belief in team processes, make RSEs sought after on the job market and their values make them responsible members of a digital society. The result is a qualification profile which is highly attractive for young people.\n\nAt an institutional level, research performing organisations have a growing interest in fostering RSE training to support the use of FAIR data and FAIR software in the academic world, a direction determined by new incentives created by scientific journals and librarians. How we update existing institutions and set up new ones that provide this education will be the topic of a follow-up paper.\n\nHeidi Seibold came up with the original idea for the deRSE23 workshop in Paderborn. Heidi Seibold, Jeremy Cohen, Florian Goth, Renato Alves, Jan Philipp Thiele, and Samantha Wittke organised the deRSE23 workshop. We thank all the participants of this community workshop! Toby Hodges conceptualised and organised the un-deRSE23 workshop together with Jan Philipp Thiele and Florian Goth. We also thank all the participants of this follow-up community workshop! Jeremy Cohen, Gerasimos Chourdakis, Magnus Hagdorn, Jean-Noël Grad, Jan Philipp Thiele, and Matthias Braun organised the deRSE24 workshop in Würzburg. We are also grateful to the participants of this third community workshop! Heidi Seibold, Jeremy Cohen, Florian Goth, Renato Alves, Jan Philipp Thiele, Jan Linxweiler, Jean-Noël Grad, and Samantha Wittke contributed the initial draft. Florian Goth supervised the project and did the project administration. Jean-Noël Grad designed and implemented the software tooling for the collaborative writing of this manuscript on GitHub. Everybody contributed to the final review and editing.\n\nThe CRediT system10 is far too generic to adequately describe the contributions of everybody in various workshops, spread over a two year period. While everybody contributed to the discussion formulating and refining the ideas, and to collaboratively writing and/or reviewing and editing the entirety of the script, some parts merit special mention. Renato Alves quickly jumped in to host the first deRSE23 workshop to take over from a sick organiser. Matthias Braun contributed early versions of the specialisations and also contributed to the survey. Leyla Jael Castro contributed to the initial draft of the example career path, and provided helpful insights in discussions on metadata. Gerasimos Chourdakis’ contributions to the paper are numerous (extensively editing large parts of the initial draft), but he especially wrote first drafts for clarifying the relationship of the RSE competencies to the SE competencies. He also designed the “Learning and teaching RSE” website.86 Simon Christ helped with typesetting and contributed the competencies’ symbols and the spell-checker script. Jeremy Cohen drafted the initial introduction and contributed the tables for RSEs in centralised RSE departments. Stephan Druskat contributed parts on proper software citation and publication and sharpened various RSE specialisations. Fredo Erxleben contributed to early discussions of the paper and added the contributions by the Helmholtz Association. Jean-Noël Grad contributed initial drafts for the ELIXIR framework and the section on the work of the HPC certification forum as well as numerous other contributions to the BibTeX infrastructure and the GitHub actions. Magnus Hagdorn drafted and supervised the ethics and values section for an RSE and made sure that these values are reflected in the competencies of RSEs. Toby Hodges contributed parts on the Carpentries, and helped steer the curriculum discussion. Guido Juckeland contributed experiences from his first RSE course for students. Dominic Kempf drafted the first version of the example curriculum. Anna-Lena Lamprecht helped with proper wording, especially with awareness about established SE terminology, that was misused earlier. Jan Linxweiler drafted various RSE specialisations and made sure that clean coding techniques got their due recognition. Frank Löffler rewrote numerous parts to be actually legible, and helped with preparation for the final steps of a de-RSE position paper. Michele Martone wrote the first draft of the environmental sustainability section. Moritz Schwarzmeier drafted the categorisation of the specialisations. Heidi Seibold contributed the idea and started everything. Jan Philipp Thiele drafted initial parts of the technical pillar of the RSE competencies, and represented the project on numerous discussions. Harald von Waldow contributed to initial drafts of the Masters program and contributed his knowledge to the explainability of computer simulations. Samantha Wittke contributed the parts on CodeRefinery and how to reach out to new RSEs. Florian Goth has the pleasure of being grateful to all collaborators in this project for contributing their time and knowledge into this project!\n\n\nEthics and consent\n\nEthical approval and consent were not required.\n\n\nGlossary\n\nbus factor vulnerability of a project to losing key and irreplaceable team members - a bus factor of 1 means that a single such team member vanishing would already stall the project’s advancement. 18\n\nC general-purpose compiled programming language. 25\n\nC++ general-purpose compiled programming language. 25\n\ndesign pattern general and reusable solution to solve a SE problem (often a best practice, or a “recipe”). 5, 11\n\nGitHub online software repository hosting and collaboration platform. 12\n\nGitLab online software repository hosting and collaboration platform. 12\n\nPython general-purpose scripting language. 25\n\nR general-purpose scripting language. 25\n\nsoftware publication the practice of long-term archiving software artifacts with software metadata under a permanent identifier. 8\n\nstatic analysis automated procedure to detect software bugs in source code without executing the code. 11\n\nSysOp system administrator in charge of a computing infrastructure. 22\n\n\nSkill codes\n\nDIST Building distributable software. 14, 16, 18, 21, 22, 25, 28\n\nDOCBB Creating documented code building blocks. 11, 12, 14, 16, 18, 21, 25, 27, 28\n\nDOMREP Using domain repositories/directories. 15, 16, 19, 26\n\nMOD Software behaviour awareness and analysis. 11, 14, 16, 18, 21, 26, 27\n\nNEW Conducting and leading research. 11, 12, 15, 16, 19, 26\n\nPM Project management. 11, 12, 15–18, 20, 21, 26, 27\n\nRC Understanding the research cycle. 11, 12, 15, 16, 19, 21, 27\n\nSP Software publication and citation. 11, 12, 15–17, 19, 21, 26, 28\n\nSRU Software re-use. 12, 15, 16, 19, 21, 25, 26\n\nSWLC Adapting to the software life cycle. 11, 12, 14, 16–18, 27\n\nSWREPOS Use software repositories. 12, 14, 16–18, 25\n\nTEACH Teaching. 15–17, 20, 21, 26, 27\n\nTEAM Working in a team. 11, 12, 15–17, 20, 21, 26, 27\n\nUSERS Interaction with users and other stakeholders. 11, 12, 15–17, 20, 21, 26, 27\n\n\nAcronyms\n\nCD continuous delivery. 27\n\nCI continuous integration. 5, 27\n\nCI/CD continuous integration and continuous delivery. 11\n\nDFG German Research Foundation (Deutsche Forschungsgemeinschaft). 5\n\nDMP data management plan. 22\n\nEMBL-EBI European Molecular Biology Laboratory - European Bioinformatics Institute. 5, 21, 28\n\nENCCS EuroCC National Competence Center Sweden. 5\n\nEU European Union. 22\n\nEuroHPC JU European High-Performance Computing Joint Undertaking. 28\n\nFAIR Findability, Accessibility, Interoperability and Reusability. 3, 6, 8, 10, 11, 21–23\n\nGDPR General Data Protection Regulation. 22\n\nGPL General Public License. 12\n\nGREENER Governance, Responsibility, Estimation, Energy and embodied impacts, New collaborations, Education and Research. 7\n\nHIFIS Helmholtz Federated IT Services. 5\n\nHPC High-Performance Computing. 5, 22, 26–28\n\nIDE integrated development environment. 11\n\nISCB International Society for Computational Biology. 28\n\nIT information technology. 6, 10, 22, 27\n\nLLM large language model. 7\n\nMIT Massachusetts Institute of Technology. 3\n\nML machine learning. 3, 22, 27\n\nNFDI National Research Data Infrastructure (Nationale Forschungsdateninfrastruktur). 5, 12\n\nPI Principal Investigator. 16, 23, 27\n\nPRACE Partnership for Advanced Computing in Europe. 5\n\nRDM research data management. 21, 22\n\nSE software engineering. 3, 5, 6, 10–12, 16, 23, 28, 32\n\nSTEM science, technology, engineering and mathematics. 3, 25\n\nTDD test-driven development. 5\n\nUK United Kingdom. 3, 5, 28\n\nUML Unified Modelling Language. 11\n\nUNESCO United Nations Educational, Scientific and Cultural Organization. 6\n\nUNIVERSE-HPC Understanding and Nurturing an Integrated Vision for Education in RSE and HPC. 5, 28",
"appendix": "Data availability statement\n\nNo data associated with this article.\n\n\nAcknowledgements\n\nWe appreciate the comments and suggestions from Yves Vincent Grossmann, Wilhelm Hasselbring, and Bernhard Rumpe.\n\n\nReferences\n\nAlves R, et al.: ELIXIR Software Management Plan for Life Sciences.2021-10. (Visited on 2022-06-23). Publisher Full Text\n\nAnzt H, et al.: An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action [version 2; peer review: 2 approved]. F1000Res. 2021; 9: 295. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nAthalye A, Gjengset J, Ortiz JJG: The Missing Semester of Your CS Education. MIT, Computer Science & Artificial Intelligence Laboratory; (visited on 2023-08-11). Reference Source\n\nBarker M, et al.: Introducing the FAIR Principles for research software. Sci Data. 2022-10; 9(1): 622. 2052-4463. 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}
|
[
{
"id": "345505",
"date": "17 Dec 2024",
"name": "Miranda Mundt",
"expertise": [
"Reviewer Expertise Research software engineering with an emphasis on testing",
"reproducibility",
"and diversity",
"FAIR(ER) principles (E = Equitable",
"R = Realistic)"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n# Paper Review - Foundational Competencies and Responsibilities of an RSE\n## Summary\nThis paper presents an idyllic image of what RSE education and career paths could be. It presents a detailed (but high-level) overview of competencies and provides example specializations. It is unclear the full intended scope (i.e., is this meant to be an emphasis on RSEs only in academia? Only in Europe? All RSEs in all roles worldwide?) Overall, this is clearly a paper that is well-considered, well-formatted, and a labor of love.\n## Specific Feedback - Scope: How large is the scope of this paper? Is it meant to encompass RSEs around the globe or focused primarily on European RSEs? Also is it meant to be aspirational (e.g., all RSEs should have these) or does it represent the current state of RSEs (e.g., most RSEs already have these competencies)?\n- Section 2 (Related Work):\n\n- Related to scope question: If this is intended to be more widespread, I recommend including references to INTERSECT (https://intersect-training.org), BSSw (https://bssw.io), and IDEAS-productivity (https://ideas-productivity.org)\n- Section 3 (Values)\n\n- I'd push back on the claim that RSEs adhere to the SE Code of Ethics purely because, as stated earlier in the paper, a lot of RSEs don't have classical training and wouldn't even necessarily know that those ethics exist. Do they probably adhere to them accidentally? Yes. But I'd suspect the average RSE couldn't reliably list anything in the SE Code of Ethics.\n\n- First paragraph, something is missing here / incomplete sentence/thought: \"Central to that code is the RSE's obligation to In addition to the values...\"\n\n- I had a bit of a hard time following the computer-based modeling paragraphs / understanding why a discussion of them was happening until the second to last sentence of the paragraph that starts with \"The relationship between initial state...\"\n- Section 3.1 (Challenges)\n\n- I notice that \"funding methods\" is missing from these challenges; there has been a lot of discussion about unreliable funding methods for software and, as a result, RSEs (e.g., https://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=6886129, https://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=9470770, https://pure.manchester.ac.uk/ws/portalfiles/portal/54140648/StateOfTheNationReport2017.pdf, https://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=10071971)\n\n- There is also a lack of \"RSEs being integrated into existing teams and having to fight that team's culture\". Maybe this is too niche to bring up, but it is a challenge that has been spoken about amongst RSE circles (e.g., \"How can I get an existing team to change their processes when they are so stuck in their ways?\")\n\n- Section 3.1.1 - this almost might be better if phrased as \"Data Security\" because that's kind of the crux of the paragraph\n\n- Section 3.1.2 - I agree with all of the points here *but* it's realistically not just up to RSEs to embrace and shape diversity. What does it mean for them to \"mitigate them whenever they have the chance to do so\"? Examples might be helpful.\n- Section 4 - can you include a footnote to any digital information on the Paderborn workshop?\n- Section 4.1.2 - there are multiple research software maturity models/frameworks that have been proposed that adapt SWLC. See, for example, M. R. Mundt, W. Burgess and D. M. Vigil, \"A Tiered Approach to Scientific Software Quality Practices,\" in Proceedings of the 2022 Improving Scientific Software Conference (No. NCAR/TN-574+PROC). doi:10.5065/98kd-b491\n- Section 4.1.5 - I recommend adding a note here for \"as applicable,\" e.g., some RSEs at some institutions may not be able to share code publicly because of security or institutional requirements (though they should still use whatever they can for version controlling)\n- Section 4.2.4 - Similar note to 4.1.5; there should be something about \"adhering to institutional policies\" as well\n- Section 4.4 (Tasks and Responsibilities)\n\n- When talking about RSE communities, it might be worth it to reference some of them, e.g., UK-RSE / Soc RSE, deRSE, US-RSE, RSE-AUNZ, RSE Asia, RSSE Africa, etc.\n- Section 5.2 (Helpful RSE skills in academic career)\n\n- I disagree with some of the claims here (e.g., license discussion for Bachelor's degree seems like too much). Generally, though, this section is nice. However...\n\n- Not all RSEs have PhDs. Most of them do, yes, but many RSEs who do NOT have PhDs are still wildly successful without having gained the proposed skills as PhD students. How do you address that scenario (i.e., where an RSE stops after a Bachelors, Masters, etc.?)\n- Section 5.3 (Project team structures) - there is a gap here: \"The single RSE on a team of not-RSEs who does not have a central RSE team connection.\" These do exist (sadly).\n- Section 5.4.1 - formatting weirdness in the Research Skills sub-list (pg 22)\n- Section 6 - This section is my favorite. I love the examples of different specializations because it allows a lot of readers to \"see\" themselves in this paper.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "345501",
"date": "26 Dec 2024",
"name": "Uwe Schmitt",
"expertise": [
"Reviewer Expertise Senior RSE in different scientific domains."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n# Summary\nThe paper addresses many aspects of working as an RSE in different roles and the skills required or recommended to work effectively and to a high standard in this area. As outlined, RSEs work in a wide variety of roles and as such the inclusion of many contributors helps to ensure that many different aspects are covered and considered. In addition, the authors outline future scenarios on how the current situation can be systematically shaped and improved. The paper is well structured and readable and makes a significant contribution to the understanding and future development of different RSE roles, required skills and training and career paths. The authors also outline future publications based on this article.\n\n# Minor corrections and suggestions.\nI think the title of the publication only describes part of the content and does not include the proposed suggestions and scenarios for the future of RSE skills development and support. A different title, along the lines of \"Foundational Competencies and Responsibilities of a Research Software Engineer: Current State and Suggestions for Future Directions\" might better describe the content of the article.\n\n## Section 3 (Values) This sentence appears to be corrupted due to editing:\n“Central to that code is the RSE’s obligation to In addition to the values for good scientific practice commit to the health, safety and welfare of the public and act in the interest of society, their employer and their clients.”\n“RSEs also adhere to the SE Code of Ethics”: As much as I agree with the proposed values, I would prefer the subjunctive/conjunctive form here, as used in other parts of the document. The teaching of these values could be strengthened in the later section proposing bachelor and master curricula.\n## Page 14 bottom:\nI recommend to separate the following two paragraphs:\nRSEs are also mentoring colleagues (see also Section 3.1.2). This necessitates giving good advice that fits to a project’s stage in its life cycle, thereby requiring knowledge of ( SWLC), and its context in its research domain and thus ( RC). **END OF PARAGRAPH HERE** Research software can often start out as a tool to answer a personal research question, becoming more important when other researchers start to rely on it. At the other end of the scale, research software can sometimes underpin key processes that deal with critical questions such as weather forecasting or medical diagnosis.\n## Table 4 The row “SLWC” mentions “bus factors” several times and may need explanation, or should be added to the glossary.\n## 5.4.1\nIndentation of the bullet points after “Research skills” seems to be broken.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1429
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https://f1000research.com/articles/13-1428/v1
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26 Nov 24
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{
"type": "Research Article",
"title": "Undernutrition before two years in Algeria: Repeated cross-sectional analyses (2012-13 to 2018-19)",
"authors": [
"Nagwa Farag Elmighrabi",
"Catharine A. K. Fleming",
"Kingsley E. Agho",
"Catharine A. K. Fleming",
"Kingsley E. Agho"
],
"abstract": "Background Algeria has made significant progress in addressing childhood undernutrition. Despite improvements, nearly 12% of Algerian children under five years of age suffered from stunting in 2022. This study aimed to evaluate the prevalence of three indicators of undernutrition (stunting, wasting, and underweight) and their associated variables in children aged 0–23 months in Algeria between 2013 and 2019.\n\nMethods Pooled data from Multiple Indicator Cluster Surveys (MICS) (2012-13 and 2018-19) covering 14,498 children were used. Univariate and multiple logistic regression analyses were performed to test the associations.\n\nResults Stunting decreased significantly, but wasting and being underweight showed no significant reductions from 2013 to 2019. Stunting, wasting, and underweight decreased by 2.2%, 1.3%, and 0.3%, respectively, with an overall prevalence of 10.1%, 5.4%, and 3.6%, respectively. Factors associated with undernutrition included child age and small size at birth, whereas stunting was linked to the poorest households, male children, higher maternal body mass index (BMI), and low antenatal care (ANC) visits. Wasting was associated with younger age and paternal age, fewer maternal ANC visits, underweight male sex, low maternal education, high maternal BMI, and delayed breastfeeding initiation.\n\nConclusion Public health experts and stakeholders must adopt a comprehensive community-centered approach to achieve long-term improvements in child nutrition in Algeria. This strategy should focus on key factors including high maternal BMI, low maternal education, male children, and infrequent ANC visits. This action can help Algeria progress towards achieving the UN’s goal of eradicating malnutrition.",
"keywords": [
"Stunting",
"wasting",
"underweight",
"young children",
"North Africa"
],
"content": "Background\n\nChild undernutrition remains a major public health issue and one of the leading causes of morbidity and mortality worldwide. The World Health Organization (WHO) states that undernutrition accounts for nearly half of all deaths in children under five globally, which could be prevented through maternal and child health interventions. According to recent global estimates, there are 149 million stunted children under five worldwide, of whom 45 million have wasting and 14.3 million severe wasting.1 Most undernourished children are in developing countries, with Asian and African countries being the most affected. In Asia, approximately 54% of children under five years of age are stunted, while 69% suffer from wasting. In Africa, approximately 40% of children under five experience stunting and 27% experience wasting.2\n\nThe WHO has reported alarming statistics that show a worrying rise in undernutrition patterns in North Africa, which runs counter to the global trend according to its release in 2021.3 In 2022, approximately 12% of children under the age of five in Algeria experienced stunting, while the prevalence of wasting in the country was 4.1% in the same year. Stunting is frequently observed in children who endure extended durations of insufficient nourishment, resulting in the depletion of vital nutrients necessary for growth.4\n\nThe seriousness of undernutrition lies in its potential to cause permanent physical and cognitive impairments in children, especially in those who experience stunting.1,2,5 The long-lasting consequences of stunting include decreased cognitive function, hindered academic performance, lower income in adulthood, reduced productivity, and an elevated risk of nutrition-related chronic diseases in the later stages of life. These effects have been observed throughout the developmental journey from adolescence to young adulthood.2,6 Insufficient nutrient intake and/or recurring illnesses can lead to wasting and pose a significant threat to life.1 When children suffer from wasting, they become more vulnerable to long-term developmental delays, weakened immunity, and elevated risk of death.1 Undernutrition not only increases the rates of child mortality and morbidity by endangering immunity and increasing susceptibility to infections, but also has broader socioeconomic ramifications and effects on family incomes, community prosperity, and productivity.2,7\n\nThis study specifically targeted children under two years of age, as evidence suggests that inadequate fetal growth and/or stunting during the first two years of life can result in irreversible effects, including shorter adult height, lower educational achievement, reduced income, and reduced birth weight of future offspring. Furthermore, children who experience undernourishment in their early years and subsequently experience rapid weight gain are susceptible to nutrition-related chronic illnesses.8 The most critical time for nutrition interventions is before and/or during the first two years, as they greatly affect child survival, health, and development.9\n\nPrevious studies have identified factors that influence undernutrition.7,10 Such factors include poverty, natural disasters, food insecurity,11,12 economic difficulties, civil wars,12 climate change13 and epidemics.14 The more prevalent detrimental factors in middle-income countries have the potential to further worsen the immediate factors associated with undernutrition, particularly maternal health,15 food intake,16 and illnesses.17 According to the findings of the Global Nutrition Report, Algeria has made considerable strides in its efforts to combat stunting. Nevertheless, it is important to highlight that 9.8% of children under the age of five are still affected, a figure that falls below the average for the African region (30.7%). Algeria is making progress toward achieving the target for wasting, as only 2.7% of children under five are affected, which is still lower than that in Africa (6.0%).18\n\nHowever, the country continues to grapple with the aforementioned factors, which collectively contribute to the perpetuation or exacerbation of malnutrition. Furthermore, the United Nations Economic and Social Commission for Western Asia (ESCWA) found that Algeria is currently grappling with a triple burden of malnutrition. The country has a high food import dependency with high costs, water scarcity, and high unemployment, which could further affect its food security. Food insecurity has emerged as a potent stressor for families with significant adverse effects on children’s health and development.19\n\nIn 2020, a publication updated the nutritional status of Eastern Algeria.20 In 2023, a systematic review and meta-analysis analyzed childhood undernutrition in North Africa, including Algeria, through a systematic review and meta-analysis study.21 However, a significant limitation of these studies is the issue of generalizability, owing to the small number of undernourished children recorded in a single dataset. Additionally, including Algeria, along with other countries, in the second study may have led to an over- or underestimation of the findings. Consequently, this study combined the two datasets to enhance statistical power and ability to compare outcomes, and to overcome the inconclusive results from a single study. This study aimed to evaluate the presence of undernutrition (stunting, wasting, and underweight) and its associated factors among children aged 0–23 months in Algeria in 2013 and 2019. The results will enhance the existing body of evidence necessary for implementing effective interventions that prioritize actions targeting the factors associated with child malnutrition in Algeria.\n\n\nMethods\n\nThis cross-sectional study utilized nationally representative data from the Algerian Multiple Indicator Cluster Surveys (MICS) conducted in 2012-13 (as part of the fourth global iteration (MICS4)), and 2018-19 (as part of its sixth edition (MICS 2018-19)). Both surveys were implemented and facilitated by the Ministry of Health, Population, and Hospital Reform (Algeria) in collaboration with the global MICS program. These efforts have received financial and technical support from UNICEF, along with financial contributions from the United Nations Population Fund (UNFPA).22,23 The MICS gathers cross-sectional data internationally to provide comparable health information, especially regarding maternal and child health. The survey encompasses the entire nation, with an emphasis on particular regions. To achieve comparability, the MICS adopt a standardized complex sampling design that incorporated multistage stratified cluster sampling, and selection probabilities are assigned to each primary unit. The surveys are available at http://mics.unicef.org/.\n\nEligible participants for data collection were all females aged 15–49 years who were either permanent residents or visitors residing in the households the night before the survey. A survey was conducted among mothers to collect data regarding the health of their youngest child, who was aged under five years. Country-specific MICS reports provide further details on the sampling method and questionnaire used. The response rate for nearly all women’s questionnaires ranged from 97% to 99%. In total, 14,498 children aged 0–23 months were included in the analysis, encompassing the two MICS surveys. The 2012-13 MICS included 7890 children (of ages 0-23 months) and the 2018-19 MICS included 6608 children.\n\nA survey was conducted among women aged 15-49 utilizing a specific questionnaire for data collection. The questionnaire asked about the participants’ educational attainment, residential location, media exposure, pregnancy history, childhood mortality rates, breastfeeding and feeding practices, vaccination and illness history during childhood, marital status, sexual activity, employment status, marital background characteristics, awareness and behaviors concerning HIV/AIDS and other sexually transmitted infections, and maternal mortality.\n\nThree indicators of undernutrition - stunting, wasting, and underweight - were used as the outcome variables in this study. The prevalence of each indicator was calculated using the 2006 WHO growth reference, which compares a child’s growth to that of a healthy child in the same age group or reference population.24 This is represented as a deviation from the median in terms of standard deviations (SDs). Stunting was defined as height-for-age (HAZ) Z-score≤−2 SD; wasting as weight-for-height (WHZ) Z-score≤−2 SD of the median and underweight as weight-for-age (WAZ) Z-score <−2 SD of the median.\n\nPotential confounding variables were chosen based on a previous study conducted in 35 low- and middle-income countries.25 The covariates included place of residence (urban/rural), pooled household wealth index, child’s age and sex, parents’ age, parents’ educational attainment and nutritional health, number of household members, birth order, marital status and age, utilization of health care services, water and sanitation conditions, access to media, early initiation and duration of breastfeeding, perceived baby size, and child illness (diarrhea, fever, cough, and any infection within the two weeks preceding the survey).\n\nTable 1 offers a detailed overview of the categorization of independent variables. To ensure better understanding, specific variables were further categorized as: The household wealth index was developed utilizing the “wscore” scores derived from the integrated datasets through the principal component’s statistical method. The combined household scores were categorized into five groups: poorest, poor, middle, rich, and richest. The lowest 20% of households represent the poorest group, whereas the highest 20% constitute the richest group. The available toilet systems comprise flush or pour-flush toilets connected to a piped sewer system, septic tank pit latrines, ventilated improved pit latrines, pit latrines with a slab, or composting toilets.26 The definition of protected sources of drinking water encompasses household connections, public standpipes, boreholes, protected dug wells, protected springs, and rainwater collection.27\n\nDescriptive analyses employed Stata ‘Svy’ (Stata Corp 17.0) commands (https://blog.stata.com/2021/04/20/stata-17-released/) to account for the cluster sample design used in the surveys, enabling the calculation of confidence intervals for prevalence values.28 Cross-tabulations were created to examine the frequencies and confidence intervals of stunting, wasting, and underweight in relation to potential confounding factors. The chi-squared test was performed to establish statistical significance. The Taylor series linearization method was used to estimate 95% confidence intervals (CIs) around the prevalence of stunting, wasting, and underweight by survey year, as shown in Figure 1. Odds ratios (ORs) were initially calculated using univariate analyses to assess the associations between stunting, wasting, and underweight. Subsequently, a stepwise backward regression model was used for multiple logistic regression analysis. Stunting, wasting, and underweight were treated as binary ependent variables. The analysis presented unadjusted ORs with 95% CIs for all potential confounding factors. Subsequently, adjusted ORs with 95% CIs were provided for variables that remained significant in the final model.\n\n\nResults\n\nThe characteristics of the study participants from the two population-based datasets (2012-13 and 2018-19) are presented in Table 1. The data for this study comprised 14498 young children aged 0-23 months in Algeria across two population-based datasets - 7890 in 2013 and 6608 in 2019. For the two population-based datasets, there was no drastic difference in the characteristics: the percentage of rural dwellers was almost equally distributed between the two population-based datasets (40% in 2012-13 vs 43 in 2018-19), and the percentage of the highest income households was similar (22% in 2012-13 and 2018-19). Other characteristics of the sample that showed little or no differences in their percentages included: boys (52% in 2012-13 and 51% in 2018-19), maternal body mass index (BMI) ≤ 18.5 kgm−2 (71% in 2012-13 and 73% in 2018-19), use of clean cooking fuel (100% for each of the periods), large baby size (19% in 2012-13 and 18% in 2018-19), 8+ antenatal care (ANC) visits (5% in 2012-13 and 7% in 2018-19), and breastfeeding within one hour of delivery (38% in 2012-13 and 36% in 2018-19).\n\nFigures 1, 2, and 3 show the trends in the three indices of undernutrition (stunting, wasting, and being underweight, respectively) from 2013 to 2019 in Algeria. There was a reduction in stunting in children aged under two. The prevalence of stunting significantly reduced by 2.2, i.e., the two bars did not cross each other, from 11.2% in 2013 to 8.8% in 2019 (p = 0.006). In 2012-13, over one in 10 children under the age of two had stunting compared to one in twelve children under two in 2018-19. However, the overall pooled prevalence rate was 10.1%, one in ten children. The prevalence of wasting decreased from 6% to 4.7% in 2019, with a p value of 0.114% and an overall prevalence of 5.4 %. Similarly, the prevalence of underweight decreased from 3.7% to 3.4%, with a p value of 0.558, and an overall prevalence of 3.6%.\n\nThe prevalence of stunting was higher among children belonging to the poorest households [prevalence, P = 14.2%; 95% CI: (11.9, 16.7)], compared with those from the richest households [unadjusted OR: 1.61; 95% CI: (1.21, 2.13)] ( Table 2); Variables for which there was increased prevalence of stunting included being in the 18-23 months age bracket [P = 13.1%; OR: 1.40; 95% CI: (1.11, 1.75)], polygamous father [P = 9.8%; OR: 1.78; 95% CI: (1.17, 2.70)], no maternal education [P = 12.0%; OR: 1.33; 95% CI: (1.08, 1.63)], maternal BMI of 25 kg/m−2 or higher [P = 45.5%; OR: 11.37; 95% CI: (6.67, 19.38)], no ANC clinics [P = 10.5%; OR: 1.45; 95% CI: (1.04, 2.01)], and breastfeeding for more than 12 months [P = 10.7%; OR: 1.28; 95% CI: (1.09, 1.51)]. Variables for which there was a decreased prevalence of stunting included large baby size at birth [P = 7.5; OR: 0.74; 95% CI: 0.57, 0.95)] and contraction of diarrhea [P = 7.8; OR: 0.73; 95% CI: 0.55, 0.99)].\n\n* P< 0.05 .\n\n** p<0.01 .\n\n*** p<0.001.\n\nVariables for which there was an increased prevalence of wasting included belonging to a household with more than eight members [P = 7.6%; OR: 1.68; 95% CI: 1.03, 2.73)] and not having ever been breastfed [P = 6.2%; OR: 1.32; 95% CI: 1.05, 1.66)]. Variables for which there was a decreased prevalence of wasting included belonging to the 18-23 months age group [P = 2.1; OR: 0.18; 95% CI: (0.12, 0.27)], paternal age > 45 years [P = 4.4%; OR: 0.58; 95% CI: (0.41, 0.80)], large size at birth [P = 3.6%; OR: 0.73; 95% CI: (0.54, 0.99)], and being breastfed for more than 12 months [P = 4.8%; OR: 0.68; 95% CI: (0.54, 0.84)].\n\nVariables for which there was an increased prevalence of underweight included no ANC clinic visits [P = 4.0%; OR: 1.04; 95% CI: 0.62, 1.73)] and no maternal education [P = 3.6%; OR: 1.29; 95% CI: 0.90, 1.85)]. Variables for which there was an increased prevalence of being underweight included being put to the breast within one hour after birth [P = 2.7%; OR: 0.66; 95% CI: (0.51, 0.84)], having been breastfed for more than 12 months [P = 3.0%; OR: 0.61; 95% CI: (0.48, 0.77)], being a girl [P = 2.9%; OR: 0.67; 95% CI: (0.50, 0.70)], belonging to the 18-23 months age group [P = 2.0%; OR: 0.26; 95% CI: (0.17, 0.39)], maternal BMI of 25 kg/m−2 or higher [P = 0.7%; OR: 0.15; 95% CI: (0.02, 1.08)], and being of a large size at birth [P = 1.7%; OR: 0.53; 95% CI: (0.36, 0.78)].\n\nThe significant factors associated with the three undernutrition categories (stunting, wasting, and underweight) are presented in Table 3. Significantly decreased odds of stunting occurred in the period 2018-19 [adjusted odds ratio (AOR) = 0.80; 95% CI: 0.66, 0.97]. The odds of stunting were significantly higher among children from the poorest households compared with those from the richest households [AOR = 1.56; 95% CI: (1.16, 2.10)]. The odds of being stunted were significantly higher among children aged 18-23 months [AOR = 1.36; 95% CI): (1.10, 1.69)]. Children whose mothers had a BMI of 25 kg/m2 or over were significantly more likely to be stunted than their counterparts whose mothers had a BMI less than 18.5 kg/m2 [AOR = 14.38; 95% CI: (7.86, 26.30)]. The odds of being stunted were significantly higher among children who were perceived as small at birth than among those who were perceived as average-sized (AOR = 1.72; 95% CI: (1.39, 2.12)]. Children whose mothers attended between 1 and 3 ANC clinics were significantly more likely to be stunted than those who attended 8 or more ANC clinics [AOR = 1.63; 95% CI: (1.15, 2.33)]. In contrast, decreased odds of stunting were associated with being female [AOR = 0.59; 95% CI: 0.50, 0.70)].\n\nIncreased odds of wasting were significantly associated with being perceived to be small at birth [AOR = 1.50; 95% CI: 1.11, 2.03)] and being a child to a mother who attended no ANC clinics [AOR = 1.82; 95% CI: (1.00, 3.29)]. Decreased odds of wasting were associated with being aged 18-23 months [AOR = 0.17; 95% CI: 0.12, 0.24)] and having a father aged 35-44 years [AOR = 0.73; 95% CI: (0.55, 0.98)].\n\nThe likelihood of being underweight was significantly higher among children whose mothers had primary education only than among their counterparts whose mothers had secondary school education or higher [AOR = 1.47; 95% CI: 1.05, 2.06)]. Children who were perceived to be small at birth were significantly more likely to be underweight than those who were perceived to be average-sized [AOR = 2.10; 95% CI: (1.54, 2.85)]. The odds of being underweight were significantly lower among girls than among boys [AOR = 0.67; 95% CI: (0.51, 0.87)]. Children aged 12-17 months were significantly less likely to be underweight than those aged 0-5 months [AOR = 0.20; 95% CI: (0.14, 0.30)]. Children whose mothers had a BMI of 19-25 kg/m2 were less likely to be underweight than those whose mothers had a BMI of 18.5 kg/m2 or less [AOR = 0.17; 95% CI: 0.12, 0.24)]. Underweight odds were significantly lower among children who were to the breast within 1 h after birth compared with those who were to the breast after 1 h (AOR = 0.67; 95% CI: [0.51, 0.87]).\n\n\nDiscussion\n\nThe current study aimed to investigate the prevalence of the three indicators of undernutrition among Algerian children under two years of age and to identify the significant factors associated with undernutrition to make progress in combating childhood undernutrition by 2030. This study combined data from the Algerian MICS surveys conducted in 2012-13 and 2018-19. Our analysis revealed a significant decline in the prevalence of stunting in the two population-based datasets. The prevalence of undernutrition was generally lower in the 2018-19 dataset compared than in the 2012-13 dataset. Multivariate analysis identified several key factors associated with undernutrition. Notably, the factors that were significant determinants across all three indices of undernutrition were child’s age and perceived size at birth. ANC visits were strongly associated with stunting and wasting, while maternal BMI and male sex were significant factors affecting both stunting and being underweight. Furthermore, we observed associations between household wealth index and the year of the survey with stunting, as well as between advanced paternal age and wasting. Maternal education level and the timing of breastfeeding initiation were also notable factors specifically associated with being underweight.\n\nAbout one in ten children in Algeria under the age of two in Algeria experienced stunting, with a positive improvement between 2012 and 2019. Contrary to the study findings, the number of children under five years of age with undernutrition worldwide has been increasing since 2014. A recent FAO report indicated that the overall prevalence of undernutrition in Africa increased from 19.4% in 2021 to 19.7% in 2022. In contrast, the prevalence of undernutrition in Asia declined from 8.8% in 2021 to 8.5% in 2022, representing a reduction of over 12 million individuals.29 It should be emphasized that the last nationally accessible survey for Algeria dates back to 2019, and no further data have been gathered or published since then. Owing to the lack of recent nationally representative data after 2019, it is difficult to determine whether the current undernutrition in Algeria after 2019 is improving or worsening, highlighting the importance of consistent data collection. These data are crucial for combating undernutrition, a complex public health issue influenced by multiple interconnected factors.15 These factors are vulnerable to various crises, both nationally and globally, such as pandemics, environmental catastrophes, civil unrest, and global conflicts.11–13 Consistent data collection can help to better understand and manage undernutrition, leading to more effective interventions and policymaking.30\n\nThe study analyses demonstrated that the prevalence of stunting was significantly higher among children belonging to the poorest households, consistent with previous research that identified an association between disparity in socioeconomic status and child health outcomes, particularly stunting.31,32 Inequality in stunting is associated with variations in access to healthcare, inadequate nutrition, and exposure to environmental contaminants, including pathogens from inadequate water, sanitation, and living conditions.33 Furthermore, there is evidence that significant gaps exist between the wealthiest and poorest 20% of the population across all age groups. In the aggregated sample, children from the lowest income families exhibited a peak stunting prevalence of 50% at 29 months, but the prevalence among those with the greatest wealth was significantly lower, 22% at 27 months. Moreover, wealthy countries seem to achieve maximum stunting at relatively early ages.34\n\nIn the current study, stunting was strongly correlated with age in children aged 18-23 months. This finding is consistent with past research, which observed that the prevalence of stunting generally remained high among children aged 2–4 years. Recent studies in low- and middle-income countries concur with the finding that the prevalence of stunting increases with a child’s age.15,35,36 This observation can be attributed to earlier deprivation, as stunting results from the accumulation of adverse exposures. The study findings may be attributed to the protective effect of breastfeeding, which is buttressed by the Islamic religion, which recommends that mothers breastfeed their babies for two years; mothers often aim to breastfeed their babies until the age of two years.37 However, despite Algeria being a Muslim country, exclusive breastfeeding in the first six months is still low (about 28.6%), even though it is still better than the rate in Egypt (13%),38 Tunisia (13.5%)39 and Libya (25.2%).40 The increased odds of stunting observed in older children may be attributed to inappropriate complementary feeding during the weaning period.41 Complementary feeding practices in the Middle East and North Africa do not meet the recommendations, with < 50% of children meeting their minimum dietary diversity (MDD) in the five target countries.42\n\nThe current study observed increased odds of stunting and being underweight among mothers with limited education. Similar findings were found in Pakistan, in a sample of 3071 Pakistani children aged 0-59 months from the Pakistan Demographic and Health Surveys (DHS) 2012-2013 found a significant association between undernutrition among children under five and mothers with low education levels.43 Similarly, a study conducted in Ethiopia aimed to evaluate stunting and its related factors in children aged 6 59 months.44 A systematic study and meta-analysis conducted in middle-income countries also found a statistically significant inverse correlation between maternal educational level and probability of being underweight.45 This finding can be explained by the ability of educated mothers to have a more comprehensive understanding of the health issues related to their children. Parents without formal education encounter challenges in interacting with healthcare providers, expressing their children’s symptoms of illness, and understanding information related to their children’s health.46 Inequality puts considerable pressure on family financial resources, restricts the utilization of healthcare services, and impedes accessibility to nutritious foods. These conditions adversely affect the nutritional health of mothers and children, increasing their susceptibility to diseases and growth disorders.37\n\nA recent study indicated that boys are considerably more prone to stunting than are girls. This disparity may be linked to behavioral variations, disparities between sexes, and the genetic susceptibility of boys to illness during early childhood.47 Similarly, a meta-analysis focusing on children under five years of age in Sub-Saharan Africa found that boys in sub-Saharan Africa had higher odds of being stunted in their early childhood than girls.48 Furthermore, previous research has suggested that boys tend to grow slightly faster than girls.49 However, they are vulnerable to nutritional deficiencies and infections. However, a meta-analysis of DHS data from 16 sub-Saharan countries48 revealed that sex-based differences in feeding practices within families might contribute to a higher risk of stunting among boys. In many African cultures, girls are valued more than boys because of their potential to contribute to agricultural labor and their perceived worth in terms of future dowry payments. Consequently, girls tend to receive better nutrition and care in many low-income African settings, which may explain why boys are more likely to experience stunting.50 However, according to a meta-analysis, undernutrition is still a consequence of an insufficient intake of nutritious food. Moreover, a previous study showed that in households experiencing food insecurity, there is a greater probability of undernutrition in girls than in boys.51\n\nThe findings indicated a significant association between perceived small birth size and a higher likelihood of wasting in children. This finding is consistent with those of a previous study conducted in Nigeria.52 Other studies from Ethiopia,53 Brazil54 and Pakistan55 corroborated this finding as they observed that perceived baby size was an accurate predictor of child growth. However, it is important to approach this finding cautiously as the methodology mothers use to estimate their babies’ sizes is not clearly understood. Insufficient maternal nutrition during pregnancy may result in low birth weight, because the developing fetus depends solely on the mother’s nutrient provision through the placenta. As a result, any nutritional deficiencies experienced by the mother can impede the fetus’s growth and development, which underscores the critical importance of prioritizing women’s health and prenatal care,56 thereby empowering mothers to give their children a stronger foundation for life. Children of mothers who did not visit any ANC clinic were significantly more prone to wasting. Previous research demonstrated a significant correlation between mothers’ lack of knowledge of child feeding practices and the occurrence of wasting.57 This corroborates our finding of an association between ANC clinic attendance and wasting, as it is at such places that mothers gain the requisite knowledge of appropriate child-feeding practices, which may be applied to prevent wasting. Children aged 18-23 months were less likely to be wasted, consistent with the findings of a previous study in Bangladesh, which indicated that the odds of wasting decreased as the child’s age increased,58 which was corroborated by previous studies.59,60\n\nThis study found that maternal BMI was inversely related to child being underweight. The mother’s BMI has been found to affect the nutritional status of a child during the pre- and post-pregnancy periods.51 Undernourishment in women of reproductive age, during pregnancy, and in children within the first two years of life creates a substantial health burden, underscoring the need for focused treatments for these groups.61 Furthermore, undernourished mothers frequently face challenges that hinder their ability to breastfeed and reduce their mental and physical vitality. This could adversely affect her capacity to care for her child.62 A previous study conducted in Rwanda documented an association between inadequate maternal nutrition and poor nutritional results.63 In Ghana, another study revealed that a mother’s BMI negatively correlated with child being underweight.64\n\nThe present study found that older children aged 18-23 months were less prone to underweight. The results of this study are consistent with the findings of Eriga et al. and Pheringxay et al., which found that children aged 13-24 months and 1212–24 months have a greater chance of being underweight.65,66 The positive association between 12-23 months and being underweight could be attributed to the fact that mothers usually pay less attention to their children when they get older, which could be because of attending work. At this stage, older siblings, other family members, or childcare centers assume the role of caregivers, which may lead to inappropriate feeding and hygiene practices.67 This ultimately makes these children more susceptible to childhood illnesses, resulting in underweight.67 According to the study analysis, breastfeeding within the first hour after birth was inversely associated with being underweight. Similarly, a previous study in Ghana reported an increased risk of wasting among children who were not breastfed within the first hour of birth.68 This is corroborated by previous studies.69–71 A study by Congo emphasized the correlation between early breastfeeding and child undernutrition, underscoring that early breastfeeding provides numerous advantages, particularly the delivery of colostrum, the initial milk produced by a new mother, which is rich in protective properties.69\n\nImproving nutrition in Algeria, particularly for women and children, is crucial for child survival, and plays a key role in the country’s economic development. Allocating resources toward nutrition is a cost-effective strategy for preventing the heavy burden of malnutrition. Additionally, investing in nutrition positively affects the health, education, and agricultural sectors.72,73 Economic approaches to addressing malnutrition can significantly boost a nation’s economy. Nutrition programs built on effective community engagement can deliver considerable social and economic benefits such as improved quality of life, increased productivity, and strong economic returns.72 For children, these investments enhance cognitive abilities, school attendance, and academic performance, resulting in long-term benefits for the educational sector.74 Given these advantages, Algeria should establish comprehensive national nutrition policies. Although the country currently has legislation and specific policies addressing undernutrition, these do not fully address the rising issue of overnutrition.75 A well-rounded nutrition policy is necessary to foster sustainable economic growth and development, targeting both undernutrition and overnutrition to ensure optimal nutrition for all and to prevent malnutrition in all forms.\n\nTo address the pressing issue of child undernutrition in Algeria, it is recommended that the implementation of a multifaceted national nutrition policy prioritize community-based interventions to improve access to nutritious food, clean water, and healthcare services, particularly in rural and disadvantaged areas, support for poverty reduction initiatives and social protection programs to address economic inequality and food insecurity, and collaboration with international organizations and stakeholders to leverage resources, expertise, and best practices in addressing child undernutrition. By adopting this comprehensive approach, Algeria can make significant strides in reducing child undernutrition, promoting healthy growth and development and fostering a strong foundation for sustainable economic growth and development.\n\nOne of the strengths of this study was that it utilized a large sample by pooling two different population-based datasets to examine changes in the prevalence of undernutrition and related determinants among Algerian children under the age of two years, enhancing statistical power and the ability to compare outcomes, whereas findings from a single study could be inconclusive. Another strength of our study is its exclusive focus on undernutrition in Algeria, which allowed for an in-depth analysis of the contributing factors specific to this country. By narrowing our focus, we gained detailed insight into the changes, unique challenges, and circumstances influencing undernutrition in this geographic area. Additionally, our study used the most recent nationally representative data from two periods with high responsive rates (97-99%), ensuring that our findings reflect the entire population and enhancing their generalizability and applicability. The implementation of a population-based design and a substantial pooled sample size guarantee that the obtained data accurately represent the entire population within the target area. This method improved the validity and reliability of results by reducing selection bias and enabling more accurate estimations of prevalence and relationships.\n\nNonetheless, this study had several limitations. MICS surveys are predominantly cross-sectional and collect data at a single moment, thereby reducing the capacity to ascertain causal associations or comprehend the dynamic causes of undernutrition. Moreover, cross-sectional statistics depend on self-reported information, which may be susceptible to recall or social desire bias, potentially resulting in errors. Finally, unaccounted for confounding variables may have affected the study outcomes.\n\n\nConclusion\n\nChild undernutrition remains a persistent and complex challenge in Algeria, with far-reaching consequences for individual health, economic productivity, and national development. The findings of this study underscore the need for a comprehensive and multifaceted approach to address the root causes of undernutrition, including poverty, limited access to healthcare and education, and inadequate nutritional knowledge. By prioritizing nutrition-sensitive interventions, investing in human capital, and fostering a coordinated response across sectors, Algeria can break the cycle of undernutrition and unlock a brighter future for its children. Ultimately, ensuring the optimal nutrition and health of Algerian children is not only a moral imperative, but also a critical investment in the country’s future prosperity and growth.\n\n\nEthics and consent\n\nEach participating country’s review boards granted ethical approval for the MICS during survey implementation. In Algeria the approval was by the ethics committee from the Algerian Ministry of Health, Population and Hospital Reform – General Directorate of Prevention and Health Promotion according to the Executive Decree No. 92–276 of 06 July 1992 on the Algerian Code of Medical Ethics. The MICS survey included informed consent statements read to respondents who had the option of accepting or declining participation. Verbal consent is typically used to obtain consent in MICS surveys. This method is frequently employed for numerous purposes. Document-Free Process for Sensitive or Personal Topics, Considering Cultural and Literacy Factors.",
"appendix": "Data availability statement\n\nThe data are available in the public domain and can be accessed through the prescribed registration on the official UNICEF website (https://mics.unicef.org/surveys) (accessed on 25 Oct 2024).\n\n\nAcknowledgments\n\nThis work represents part of the primary author’s PhD dissertation at the School of Health Sciences, Western Sydney University.\n\n\nReferences\n\nWorld Health Organisation: Malnutrition impact.[cited 2024 Sep 2]. Reference Source\n\nUnited Nations Children’s Fund, Wprld Health Organisation, International Bank for Reconstruction and Development/The World Bank: Levels and trends in child malnutrition: United Nations Children’s Fund World Health Organisation/World Bank Group Joint Child Malnutrition Estimates: Key findings of the 2022 editions. Geneva: WHO; 2022.\n\nUnited Nations Children’s Fund World Health Organisation: International bank for reconstruction and development/the World. Levels and trends in child malnutrition: key findings of the 2021 edition of the joint child malnutrition estimates. Geneva: World Health Organisation; 2021.\n\nStatista: Prevalence of malnutrition among children in Algeria 2022 by condition.[cited 2024 Sep 2]. Reference Source\n\nDe Onis M, Branca F: Childhood stunting: a global perspective. Matern. Child Nutr. 2016; 12: 12–26. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUNICEF Data: Monitoring the situation of children and women: child malnutrition.[cited 2024 Sep 2]. Reference Source\n\nStalin P, Bazroy J, Dimri D, et al.: Prevalence of underweight and its risk factors among under five children in a rural area of Kancheepuram District in Tamil Nadu, India. IOSR-J Dental Med. Sci. 2013; 3(6): 71–74.\n\nVictora CG, Adair L, Fall C, et al.: Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008; 371(9609): 340–357. 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Final report.2019.\n\nWorld Health Organization: WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. World Health Organization; 2006.\n\nLi Z, Kim R, Vollmer S, et al.: Factors associated with child stunting, wasting, and underweight in 35 low-and middle-income countries. JAMA Netw. Open. 2020; 3(4): e203386-e. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInternational Energy Agency: Chapter 2: Access to Clean Fuels and Technologies for Cooking. Tracking SDG 7: The Energy Progress Report.2022.\n\nMonitoring: [cited 2024 Sep 2]. Reference Source\n\nStataCorp: Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC; 2021.\n\nWorld Health Organization: The State of Food Security and Nutrition in the World 2023: Urbanization, agrifood systems transformation and healthy diets across the rural–urban continuum. Food & Agriculture Org; 2023; vol. 2023. .\n\nUnited Nations: The Sustainable development goals report. United Nations; 2022.\n\nLi Z, Li M, Subramanian SV, et al.: Assessing levels and trends of child health inequality in 88 developing countries: from 2000 to 2014. Glob. Health Action. 2017; 10(1): 1408385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWali N, Agho KE, Renzaho AM: Factors associated with stunting among children under 5 years in five South Asian countries (2014–2018): Analysis of demographic health surveys. Nutrients. 2020; 12(12): 3875. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVictora CG, Wagstaff A, Schellenberg JA, et al.: Applying an equity lens to child health and mortality: more of the same is not enough. Lancet. 2003; 362(9379): 233–241. PubMed Abstract | Publisher Full Text\n\nKarlsson O, Kim R, Moloney GM, et al.: Patterns in child stunting by age: A cross-sectional study of 94 low-and middle-income countries. Matern. Child Nutr. 2023; 19(4): e13537. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarriott BP, White A, Hadden L, et al.: World Health Organization (WHO) infant and young child feeding indicators: associations with growth measures in 14 low-income countries. Matern. Child Nutr. 2012; 8(3): 354–370. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhutta ZA, Das JK, Rizvi A, et al.: Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013; 382(9890): 452–477. PubMed Abstract | Publisher Full Text\n\nYashmin S: Islamic and cultural practices in breastfeeding. Australian Midwifery News. 2017; 17(1): 49–51.\n\nMinistry of Health and Population [Egypt], El-Zanaty and Associates [Egypt], & ICF International: Egypt Demographic and Health Survey 2014. Cairo, Egypt and Rockville, Maryland, USA: Ministry of Health and Population and ICF International; 2015.\n\nGlobal Nutrition Report: Country Nutrition Profile: Tunisia. Bristol, UK: Development; 2024.\n\nZiuo F: Awareness of Libyan Mothers About Child Feeding Practices in Benghazi, Libya. Khalij-Libya Journal of Dental and Medical Research. 2021; 5(1): 17–21. Publisher Full Text\n\nMittal A, Singh J, Ahluwalia SK: Effect of maternal factors on nutritional status of 1-5-year-old children in urban slum population. Indian J. Community Med. 2007; 32(4): 264–267. Publisher Full Text\n\nShaker-Berbari L, Qahoush Tyler V, Akik C, et al.: Predictors of complementary feeding practices among children aged 6–23 months in five countries in the Middle East and North Africa region. Matern. Child Nutr. 2021; 17(4): e13223. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan S, Zaheer S, Safdar NF: Determinants of stunting, underweight and wasting among children< 5 years of age: evidence from 2012-2013 Pakistan demographic and health survey. BMC Public Health. 2019; 19: 1–15. Publisher Full Text\n\nMuche A, Dewau R: Severe stunting and its associated factors among children aged 6–59 months in Ethiopia; multilevel ordinal logistic regression model. Ital. J. Pediatr. 2021; 47: 1–10.\n\nRezaeizadeh G, Mansournia MA, Keshtkar A, et al.: Maternal education and its influence on child growth and nutritional status during the first two years of life: a systematic review and meta-analysis. Eclinicalmedicine. 2024; 71: 102574. Publisher Full Text\n\nKhattak UK, Iqbal SP, Ghazanfar H: The role of parents’ literacy in malnutrition of children under the age of five years in a semi-urban community of Pakistan: a case-control study. Cureus. 2017; 9(6). Publisher Full Text\n\nSvefors P, Rahman A, Ekström EC, et al.: Stunted at 10 years. Linear growth trajectories and stunting from birth to pre-adolescence in a rural Bangladeshi cohort. PLoS One. 2016; 11(3): e0149700. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWamani H, Åstrøm AN, Peterson S, et al.: Boys are more stunted than girls in sub-Saharan Africa: a meta-analysis of 16 demographic and health surveys. BMC Pediatr. 2007; 7: 1–10. Publisher Full Text\n\nPrado EL, Jimenez EY, Vosti S, et al.: Path analyses of risk factors for linear growth faltering in four prospective cohorts of young children in Ghana, Malawi and Burkina Faso. BMJ Glob. Health. 2019; 4(1): e001155. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGarcia Cruz LM, González Azpeitia G, Reyes Súarez D, et al.: Factors associated with stunting among children aged 0 to 59 months from the central region of Mozambique. Nutrients. 2017; 9(5): 491. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBain LE, Awah PK, Geraldine N, et al.: Malnutrition in Sub–Saharan Africa: burden, causes and prospects. Pan Afr. Med. J. 2013; 15(1): 120. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkombi BJ, Agho KE, Merom D, et al.: Multilevel analysis of factors associated with wasting and underweight among children under-five years in Nigeria. Nutrients. 2017; 9(1): 44. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDabale GA, Sharma MK: Determinants of wasting among under-five children in Ethiopia: (a multilevel logistic regression model approach). Int. J. Stats. Med. Res. 2014; 3(4): 368–377. Publisher Full Text\n\nVitolo MR, Gama CM, Bortolini GA, et al.: Some risk factors associated with overweight, stunting and wasting among children under 5 years old. J. Pediatr. 2008; 84: 251–257. PubMed Abstract | Publisher Full Text\n\nHasnain SF, Hashmi SK: Consanguinity among the risk factors for underweight in children under five: a study from rural Sindh. J. Ayub. Med. Coll. Abbottabad. 2009; 21(3): 111–116. PubMed Abstract\n\nNational Population Commission: Nigeria demographic and health survey 2013. National Population Commission, ICF International; 2013.\n\nToma TM, Andargie KT, Alula RA, et al.: Factors associated with wasting and stunting among children aged 06–59 months in South Ari District, Southern Ethiopia: a community-based cross-sectional study. BMC Nutr. 2023; 9(1): 34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHossain MM, Abdulla F, Rahman A: Prevalence and determinants of wasting of under-5 children in Bangladesh: Quantile regression approach. PLoS One. 2022; 17(11): e0278097. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIslam MR, Rahman MS, Rahman MM, et al.: Reducing childhood malnutrition in Bangladesh: the importance of addressing socio-economic inequalities. Public Health Nutr. 2020; 23(1): 72–82. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDarteh EKM, Acquah E, Darteh F: Why are our children wasting: Determinants of wasting among under 5s in Ghana. Nutr. Health. 2017; 23(3): 159–166. PubMed Abstract | Publisher Full Text\n\nBlack RE, Victora CG, Walker SP, et al.: Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013; 382(9890): 427–451. Publisher Full Text\n\nSmith LC, Ruel MT, Ndiaye A: Why is child malnutrition lower in urban than in rural areas? Evidence from 36 developing countries. World Dev. 2005; 33(8): 1285–1305. Publisher Full Text\n\nHabyarimana F: Key determinants of malnutrition of children under five years of age in Rwanda: Simultaneous measurement of three anthropometric indices. Afr. Popul. Stud. 2016; 30(2). Publisher Full Text\n\nBoah M, Azupogo F, Amporfro DA, et al.: The epidemiology of undernutrition and its determinants in children under five years in Ghana. PLoS One. 2019; 14: e0219665. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEriga F, Gulom G, Alege JB: Predictors of under-weight among children younger than 24 months in Nimule Border Town, Eastern Equatoria State, South Sudan: a community-based cross sectional study. BMC Public Health. 2024; 24(1): 1400. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPhengxay M, Ali M, Yagyu F, et al.: Risk factors for protein–energy malnutrition in children under 5 years: study from Luangprabang province, Laos. Pediatr. Int. 2007; 49(2): 260–265. PubMed Abstract | Publisher Full Text\n\nNakahara S, Poudel KC, Lopchan M, et al.: Availability of childcare support and nutritional status of children of non-working and working mothers in urban Nepal. Am. J. Hum. Biol. 2006; 18(2): 169–181. PubMed Abstract | Publisher Full Text\n\nGarti H, Bukari M, Wemakor A: Early initiation of breastfeeding, bottle feeding, and experiencing feeding challenges are associated with malnutrition. Food Sci. Nutr. 2023; 11(9): 5129–5136. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKismul H, Acharya P, Mapatano MA, et al.: Determinants of childhood stunting in the Democratic Republic of Congo: further analysis of Demographic and Health Survey 2013–14. BMC Public Health. 2018; 18: 1–14. Publisher Full Text\n\nMuchina EN, Waithaka PM: Relationship between breastfeeding practices and nutritional status of children aged 0-24 months in Nairobi, Kenya. Afr. J. Food Agric. Nutr. Dev. 2010; 10(4). Publisher Full Text\n\nShine S, Tadesse F, Shiferaw Z, et al.: Prevalence and associated factors of stunting among 6-59 months children in pastoral community of Korahay Zone, Somali Regional State, Ethiopia 2016. J Nutr Disorders Ther. 2017; 7(208): 2161.\n\nHoddinott J, Alderman H, Behrman JR, et al.: The economic rationale for investing in stunting reduction. Matern. Child Nutr. 2013; 9: 69–82. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSoriano B, Garrido A: How important is economic growth for reducing undernourishment in developing countries? Food Policy. 2016; 63: 87–101. Publisher Full Text\n\nFood and Agriculture Organisation: ncorporating Nutrition Considerations into Development Policies and Programmes: Brief for policy-makers and programme planners in developing countries. United Nations: Food and Agricultre Organisation; 2004.\n\nSunguya BF, Ong KI, Dhakal S, et al.: Strong nutrition governance is a key to addressing nutrition transition in low and middle-income countries: review of countries’ nutrition policies. Nutr. J. 2014; 13: 1–10."
}
|
[
{
"id": "355576",
"date": "16 Jan 2025",
"name": "Om Raj Katoch",
"expertise": [
"Reviewer Expertise Economics of Nutrition"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript “Undernutrition before two years in Algeria: Repeated cross-sectional analyses (2012-13 to 2018-19)\" offers valuable insights into undernutrition among children in Algeria. However, several areas require clarification and improvement:\nThe methodology section lacks details on the calculation of undernutrition indicators—stunting, wasting, and underweight. Definitions and formulas, such as stunting being a height-for-age Z-score (HAZ) below -2 SD of WHO standards, must be specified. Indicate the software or statistical tools (e.g., WHO Anthro, R, Stata, SPSS) used for analysis. The discussion would benefit from comparing findings with existing literature. The authors should explore contributing factors, such as improved maternal education and healthcare access, and situate these findings within regional trends. The manuscript should explicitly acknowledge the limitations of the study. What are the policy implications of the study to the study are or to the world.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "13178",
"date": "22 Jan 2025",
"name": "Nelmighrabi Elmighrabi",
"role": "Author Response",
"response": "Dear Om Raj Katoch, Thank you for your valuable feedback on my manuscript, “Undernutrition before two years in Algeria: Repeated cross-sectional analyses (2012-13 to 2018-19).\" I have carefully considered your comments, and here is a response to each of your comments, outlining the changes made and providing clarification where necessary. I hope these address your concerns and enhance the clarity and quality of the manuscript. 1. The methodology section lacks details on the calculation of undernutrition indicators—stunting, wasting, and underweight. Definitions and formulas, such as stunting being a height-for-age Z-score (HAZ) below -2 SD of WHO standards, must be specified. Indicate the software or statistical tools (e.g., WHO Anthro, R, Stata, SPSS) used for analysis 1. Author response: The \"Outcome Variables\" subheading describes three undernutrition indicators—stunting, wasting, and underweight—and their calculation methods. STATA 2017 software was utilised software for the analysis, and we specified that in the data analysis subheading that descriptive analyses were conducted using Stata ‘Svy’ commands (Stata Corp 17.0). 2. The discussion would benefit from comparing findings with existing literature. The authors should explore contributing factors, such as improved maternal education and healthcare access, and situate these findings within regional trends. 2. Author response: We strongly agree with this observation. However, due to the limited literature available, to the best of our knowledge, we have addressed this by comparing our results with studies from other countries that share similar circumstances. Specifically, we have included comparisons in nearly every paragraph of the discussion section, such as \"The findings indicated a significant association between perceived small birth size and a higher likelihood of wasting in children. This finding is consistent with those of a previous study conducted in Nigeria.52 Other studies from Ethiopia,53 Brazil54 and Pakistan 55\", \"The present study found that older children aged 18–23 months were less prone to underweight. The results of this study are consistent with the findings of Eriga et al. and Pheringxay et al., which found that children aged 13-24 months and 12-24 months have a greater chance of being underweight. \" 65,66 and \"The current study observed increased odds of stunting and being underweight among mothers with limited education. Similar findings were found in Pakistan, in a sample of 3071 Pakistani children aged 0-59 months from the Pakistan Demographic and Health Surveys (DHS) 2012-2013 found a significant association between undernutrition among children under five and mothers with low education levels. 43 Similarly, a study conducted in Ethiopia aimed to evaluate stunting and its related factors in children aged 6–59 months.44 A systematic study and meta-analysis conducted in middle-income countries also found a statistically significant inverse correlation between maternal educational level and probability of being underweight.45 \" - We also agree with your suggestion regarding the importance of exploring contributing factors. This aspect has been discussed in the manuscript, particularly in the discussion section, where we highlighted healthcare access and maternal education as factors that also associated with undernutrition in Algeria. \" Children of mothers who did not visit any ANC clinic were significantly more prone to wasting. Previous research demonstrated a significant correlation between mothers’ lack of knowledge of child feeding practices and the occurrence of wasting.57 This corroborates our finding of an association between ANC clinic attendance and wasting, as it is at such places that mothers gain the requisite knowledge of appropriate child-feeding practices, which may be applied to prevent wasting.\" and \"The current study observed increased odds of stunting and being underweight among mothers with limited education. Similar findings were found in Pakistan; a sample of 3071 Pakistani children aged 0-59 months from the Pakistan Demographic and Health Surveys (DHS) 2012-2013 found a significant association between undernutrition among children under five and mothers with low education levels.43 Similarly, a study conducted in Ethiopia aimed to evaluate stunting and its related factors in children aged 6–59 months. 44A systematic study and meta-analysis conducted in middle-income countries also found a statistically significant inverse correlation between maternal educational level and probability of being underweight.45\". 3. The manuscript should explicitly acknowledge the limitations of the study. 3. Author response: The limitations of this study were clearly articulated in the final paragraph of the discussion. 4. What are the policy implications of the study to the study are or to the world? 4. Author response: Policy implications and recommendations have been addressed and stated in the discussion section of the manuscript, specifically before the last two paragraphs that discuss the strengths and limitations of the study. Please feel free to share any additional feedback. Best regards, Nagwa Elmighrabi"
}
]
}
] | 1
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https://f1000research.com/articles/13-1428
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https://f1000research.com/articles/13-1426/v1
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26 Nov 24
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{
"type": "Systematic Review",
"title": "The effects of teaching strategies on learning to think critically in primary and secondary schools: an overview of systematic reviews",
"authors": [
"Andrew D. Oxman",
"Allen Nsangi",
"Laura Martínez García",
"Margaret Kaseje",
"Laura Samsó Jofra",
"Daniel Semakula",
"Heather Munthe-Kaas",
"Sarah E. Rosenbaum",
"Andrew D. Oxman",
"Allen Nsangi",
"Laura Martínez García",
"Margaret Kaseje",
"Laura Samsó Jofra",
"Daniel Semakula",
"Sarah E. Rosenbaum"
],
"abstract": "Background We conducted an overview of systematic reviews about the effects of teaching strategies that can be used to teach primary and secondary school students to think critically. Our objective was to inform decisions about what teaching strategies to use in resources that we developed to teach critical thinking about health in secondary schools.\n\nMethods We mapped characteristics of systematic reviews of teaching strategies and summarised findings from the most relevant reviews to teaching students to think critically about health. We included reviews that assessed the effects of teaching strategies that could potentially be used in primary or secondary schools to teach students to think critically, had a Methods section with explicit selection criteria, reported at least one outcome measure of the ability to undertake one of four basic types of cognitive tasks (memory, procedural, comprehension, or opinion), and were published after 1999.\n\nResults We included 326 systematic reviews. The reviews evaluated a wide range of teaching strategies for a variety of purposes. Important limitations of the reviews included not considering adverse effects (99% of the reviews), not assessing the risk of bias for included studies (93% of the reviews), and not assessing the credibility of subgroup effects (100% of the reviews). We summarised the findings for 37 teaching strategies that we considered most relevant. The certainty of the evidence of the effects varied from very low to moderate. We used 12 of the strategies in resources that we developed to teach secondary students to think critically about health.\n\nConclusions A tremendous amount of work has gone into evaluating the effects of a wide range of teaching strategies. The results of this research can inform decisions about how to teach critical thinking and future research. However, well-designed, up-to-date systematic reviews are still needed for many teaching strategies.",
"keywords": [
"Teaching strategies",
"Critical thinking",
"Health",
"Systematic reviews"
],
"content": "Introduction\n\nWe designed the Be Smart about your Health resources for secondary school teachers and their students (in the 8th or 9th year of school, age 13-15) in Kenya, Rwanda, and Uganda.1 The aim of these resources is to help students cope with the abundance of information and misinformation about how to care for their health. Critical thinking is important for making informed choices and it is a core competency in the curricula for all three countries.2–4 However, it is often not taught in the classroom, partly due to a lack of carefully developed educational resources, and a lack of information about effective teaching strategies. The Be Smart about your Health resources were developed to help fill this gap. These resources focus on critical thinking about health actions – things that people do to care for their health or the health of others. Critical thinking about health actions is especially important because:\n\n• Good health is essential for daily life and depends on informed health choices, which depend on critical thinking about health actions.\n\n• Health is important to everyone, which makes it a good starting point for learning critical thinking skills that students can transfer to other subjects, such as the environment.5\n\nThe Be Smart about your Health resources focus on nine key concepts that people need to understand and apply when deciding what to believe about the effects of health actions and what to do.6,7 We undertook this overview of systematic reviews of the effects of teaching strategies to inform the design those resources.\n\nLearning to think critically is widely held to be an aim of education.8 However, there is not agreement on the definition of “critical thinking”, or which frameworks (conceptual structures intended to serve as a support or guide) best support critical thinking.9–13 Ennis has defined critical thinking as “reasoned, reflective thinking focused on deciding what to believe or do”,14 and we use that definition in this overview.15\n\nThinking evolved to help us choose what to do to achieve our goals after taking account of estimates of the likely effects of our actions.16 A fundamental goal of critical thinking is to improve decision making by increasing the likelihood that we will believe and act on those claims that are more likely to help us achieve our goals.17\n\nDefinitions of teaching (instructional, or pedagogical) strategies (techniques, methods, or approaches) vary. Some authors distinguish between strategies, techniques, methods, and approaches. However, there is overlap in how these terms are used. Our focus is on “different ways of helping students to learn - that is, different ways of helping them to achieve the learning outcomes that [teachers] have decided are important”.18 We refer to these as “teaching strategies”.\n\nThere are several lists of teaching strategies, organised in different ways.18–24 Beck surveyed 25 teacher education textbooks and was unable to find two similar lists of teaching strategies.19 Pomerance and colleagues reviewed 48 textbooks for elementary and secondary teacher training and found that none of the textbooks accurately described six fundamental instructional strategies.24 At most, only two of the six were covered in any textbook, and when textbooks did mention the strategies (allowing for a broad range of terminology and descriptions), the discussion could be as brief as 1-2 sentences.\n\nAlthough our specific interest is in primary and secondary school students and critical thinking outcomes, we have not limited this overview to that population or those outcome measures. There are four reasons for this. First, there are not many reviews that focus specifically on critical thinking.25–36 To the extent that those reviews do consider the effects of specific strategies, they tend to be broad categories and comparisons of strategies tend to be made indirectly (in meta-regression analyses). For example, Abrami and colleagues explored differences in the effect of three types of instruction (dialogue; authentic or anchored instruction; and mentoring, coaching, or tutoring) across 341 comparisons with different populations, outcome measures, and study designs.25 Thus, an overview that only included critical thinking as an outcome would be limited.\n\nSecond, although some learning outcomes may be of little relevance to learning to think critically, it is difficult to specify a priori which outcomes are completely irrelevant and which might provide useful information despite not directly measuring critical thinking. For example, on the one hand it can be argued that outcome measures that only require retention of knowledge are irrelevant to critical thinking. On the other hand, it is important that students have knowledge of key concepts (principles for critical thinking)7,37 and that they retain that knowledge. Other outcome measures, such as reading comprehension or understanding of science texts, are dependent on a range of factors in addition to critical thinking.\n\nThird, many reviews are not limited to primary or secondary school interventions and may or may not explore differences in effects across different students. Although some teaching strategies might be expected to have different effects for different types of students, it is uncertain whether this is the case. Starting out with an overly narrow focus in terms of the students could result in an overview that is far less informative than it might otherwise be.\n\nFourth, we were unsure how many potentially useful systematic reviews of teaching strategies there were and what the characteristics of those reviews were.\n\nFor these reasons, we conducted an overview to characterise the range of systematic reviews of teaching strategies that can potentially inform the design of resources to help primary and secondary school students learn to think critically. The overview may be useful to researchers, teachers, policymakers, and others with an interest in other learning outcomes and students. It enabled us to make an informed decision about which reviews were most useful for our specific interests.1\n\n\nObjectives\n\nOur primary objectives were to provide an overview of what is known from systematic reviews about the effects of teaching strategies that can be used to teach primary and secondary school students to think critically and inform the design of educational resources (the Be Smart about your Health resources) to teach lower secondary school students in East Africa to think critically about health claims and choices.\n\nSecondary objectives were to:\n\n• Map characteristics of systematic reviews of teaching strategies\n\n• Identify needs and priorities to assess teaching strategies based on the findings of the included systematic reviews\n\n• Identify needs and priorities to assess systematic reviews of the effects of teaching strategies\n\n• Inform the development of a framework for types of teaching strategies\n\n\nMethods\n\nThe protocol for this overview was published in Zenodo in December 2019.38\n\nWe included systematic reviews that:\n\n• assess the effects of teaching strategies (different ways of helping students to learn) that can potentially be used in primary or secondary schools to teach students to think critically,\n\n• have a Methods section with explicit selection criteria,\n\n• report at least one outcome measure of the ability to undertake one of four basic types of cognitive tasks (memory, procedural, comprehension, or opinion),39 and\n\n• were published after 1999.\n\nWe excluded reviews of teaching strategies that were restricted to:\n\n• professional students (e.g., medical or nursing students) other than teacher training\n\n• special education (teaching children and youth with disabilities)\n\n• creative or physical skills such as artistic, cooking, musical, or physical skills\n\nDoyle defined the four basic types of cognitive tasks noted above as follows39:\n\n1. memory tasks in which students are expected to recognize or reproduce information previously encountered (e.g., memorize a list of spelling words or lines from a poem);\n\n2. procedural or routine tasks in which students are expected to apply a standardized and predictable formula or algorithm to generate answers (e.g., solve a set of subtraction problems);\n\n3. comprehension or understanding tasks in which students are expected to (a) recognize transformed or paraphrased versions of information previously encountered, (b) apply procedures to new problems or decide from among several procedures those which are applicable to a particular problem (e.g., solve “word problems” in mathematics), or (c) draw inferences from previously encountered information or procedures (e.g., make predictions about a chemical reaction or devise an alternative formula for squaring a number);\n\n4. opinion tasks in which students are expected to state a preference for something (e.g., select a favourite short story).\n\nThese tasks roughly correspond with Bloom’s taxonomy, which has six main categories of intellectual abilities and skills: knowledge, comprehension, application, analysis, synthesis, and evaluation.40 Bloom’s taxonomy is well known and has clear definitions, but it difficult to make clear distinctions between the higher-order categories.11 For the purposes of this overview, we considered any task that requires judgement (‘evaluation’ in Bloom’s taxonomy) as ‘opinion tasks’ including judgements about what to believe and what to do.\n\nWe created an initial list of potentially relevant teaching strategies (Box 1) by reviewing several lists.18–23,41 We started with Beck’s taxonomy,19 which we adapted and reorganised, considering other teaching strategies and ways of categorising these. We continued to develop this list of terms iteratively, based on the literature that we retrieved and input from educational researchers and teachers.\n\nDidactic strategies (instruction in which information is presented directly from the teacher to the student, in which the teacher selects the topic, controls instructional stimuli, obligates a response from the student, evaluates responses, and provides reinforcement for correct responses and feedback for incorrect ones)\n\nDirect instruction, lectures, textbooks, picture books, audio-visual aids, podcasts, multimedia instruction, demonstration, modelling, mini lessons, reading, graphic presentations, combined graphic and verbal presentations, narrative text, comics, humour, scaffolding, pre-teaching vocabulary, link abstract concepts with concrete representations\n\nQuestioning techniques (methods used for constructing and presenting questions in order to promote effective discussions and learning or to elicit information)\n\nSocratic method, open ended questions, closed questions, interviewing, prompting, probing, redirecting, wait time, clickers, pose probing questions, oral or written reports, cloze, “assess to boost retention”, quizzes, ask and answer deep questions\n\nDiscussion strategies\n\nClassroom discussion, small group discussion, buzz sessions, brainstorming, round table, debate, structured controversy, magic circle, fishbowl dialogue, four sides/corners strategy, reflective discussion, flipped classroom\n\nRole playing\n\nRead aloud, readers’ theatre, dramatic play, storytelling, mock trial, simulation, learning games, public speaking, and speech writing\n\nProblem-based learning\n\nEnquiry-based learning, exploration-based learning, student research, research projects, learning through experimentation, science fairs, science Olympics, using case studies to teach, laboratory teaching methods, field trips, discovery learning, analytic memo, concept attainment, concept formation, concept maps, graphic organizer, knowledge map, cognitive organiser, mind mapping, structured overview, “repeatedly alternating problems with their solutions provided and problems that students must solve”\n\nRepetition and progression\n\nDistributed practice, space learning over time, spaced learning, pacing, learning targets, learning progression, competency-based learning, sequential approach, explicit teaching, interdisciplinary teaching\n\nAssessment techniques\n\nFeedback, classroom assessment techniques, formative assessment, background knowledge probe, the one-minute paper, traffic light cards, muddiest point, what’s the principle, problem recognition task, student generated test questions, classroom opinion polls, directed paraphrasing, pro and con grid, student goals ranking, course-related interest and skills checklist, self-diagnostic learning logs, misconception/preconception check, empty outlines, invented dialogues, diagnostic teaching, precision teaching\n\nCollaborative learning (a situation in which two or more people learn or attempt to learn something together)\n\nDyads, partners, cross/multi-age groups, ability and interest groups, heterogeneous groups, homogeneous groups, cooperative learning, heads together strategy, numbered heads together strategy, jigsaw teaching technique, team learning, peer teaching, peer partner learning, reciprocal teaching, readers’ workshop, reading buddies, think-ink-pair-share learning strategy, think-pair-share learning strategy, heterogeneous grouping, homogeneous grouping, multiple intelligences activities\n\nIndividual learning\n\nIndividualized instruction, learner-controlled instruction, self-paced learning, independent study, programmed learning, contract learning, mastery learning, tutorial instruction, learning centres, menus, course packets, teaching tailored to students’ learning styles, Dalton plan, writing, writing to inform, paraphrasing, pause and reflect, journal writing, homework, practice, anchor activities\n\nE-learning (using electronic devices, applications, or processes to acquire or transfer knowledge, attitudes, or skills through study, instruction, or experience)\n\nOnline learning, web-based learning, web-based instruction, Web Quest, computer-based training, mobile learning, virtual classrooms, webinars, interactive e-lessons, online discussions, electronic simulations, audio/video recording\n\nIn-service teacher training\n\nMicroteaching, powerful pedagogical strategies, team teaching, scaffolding, peer teaching, teachers’ guides, or any of the other teaching strategies listed above\n\nStarting with the terms in Box 1, we developed search strategies for Education Research Complete (EBSCO) and for Education Resources Information Center (ERIC) (Ovid).70 The searches were conducted October 13, 2019 (EBSCO) and October 29, 2019 (ERIC). We updated the searches March 15, 2022 (ERIC) and March 22, 2022 (EBSCO).\n\nTwo authors independently screened the titles and abstracts identified in October 2019 to identify systematic reviews that met our inclusion criteria. Disagreements were resolved by discussion, involving a third author if needed. We pilot tested the selection criteria on a sample of 100 records as training, before screening the search results. We retrieved the full text of articles that appeared to meet the selection criteria and two authors independently assessed each article for inclusion. Cochrane Response42 screened the updated search and selected reviews for inclusion in the same way.\n\nFor each systematic review included in the overview two review authors independently collected the following data:\n\n• Year of the last search\n\n• Number of included studies\n\n• Countries where included studies were done\n\n• School subjects\n\n• Education level of participants\n\n• Age of participants\n\n• Teaching strategies that were evaluated and their definitions\n\n• Outcome measures included in the review\n\n• Consideration of adverse effects\n\n• Included study designs (randomized trials, non-randomized studies, mixed)\n\n• Assessment of the risk of bias for effect estimates\n\n• Limitations of estimates for effect modifiers considered by the review authors\n\nCochrane Response collected the data for included reviews identified by the updated search in the same way.\n\nWe mapped characteristics of the included systematic reviews. We used a framework thematic synthesis approach to categorise the teaching strategies.43,44 This entailed four stages: familiarisation, coding, charting and interpretation of the data. We started with the framework shown in Box 1. The definitions and boundaries of each category of strategies were discussed among the review authors, and the framework was revised in line with categories that emerged from the data.\n\nWe assessed the relevance of each included review for teaching critical thinking in primary and secondary schools. These judgements were discussed by the review team and a consensus was reached on the systematic reviews that were most relevant to the design of the Be Smart about your Health resources. For each teaching strategy that we considered relevant, one review author prepared a summary based on the included systematic reviews. The other authors reviewed and edited those summaries. Each summary included an explanation of the strategy, when and why it should be used, a bottom line, and a judgement of the certainty of the evidence for the bottom-line using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.45,46 We did not do this for the reviews identified by the updated search, which was conducted after the Be Smart about your Health resources had been designed and pilot tested.\n\nEthical approval was not required for this work.\n\n\nResults\n\nWe identified 9280 records - 6499 records in the search conducted in October 2019 and 2781 records in the updated search conducted in March 2022 ( Figure 1). After removing duplicates, we screened a total of 8110 records and assessed 685 full-text reports for eligibility. We included a total of 326 systematic reviews of teaching strategies that reported at least one quantitative cognitive outcome measure applicable to primary or secondary schools.70\n\nThe number of systematic reviews of teaching strategies published each year increased from two in 2000 to 56 in 2020 ( Figure 2). Just over 40% of the reviews (132 reviews; 40.5%) were published in seven journals: Review of Educational Research (40; 12.3%), Educational Research Review (25; 7.7%), Educational Psychology Review (17; 5.2%), Computers & Education (15; 4.6%), Journal of Educational Psychology (15; 4.6%), Journal of Computer Assisted Learning (10; 3.1%), and Journal of Educational Computing Research (10; 3.1%).\n\nAmong the 226 reviews (69.3%) that reported the year of the last search, the difference between the year of publication and the year of the last search was two or more years for 151 reviews (64.5%). The year of the last search was not reported for 100 (30.7%) of the included reviews.\n\nThe reviews included between 5 and 1105 studies (median 34). The studies were conducted in over 60 different countries. Most studies were conducted in high-income countries. Studies from 16 countries were included in 10 or more reviews ( Table 1). Studies from the USA were included in at least 110 reviews (32.8%). However, 204 reviews (62.6%) did not report the countries in which included studies were conducted and other reviews only partially reported the countries in which included studies were conducted.\n\nThe education level of the included participants varied widely within and across reviews ( Table 2). Over 100 of the included reviews (104; 31.9%) included studies with participants ranging from preschool or primary school through university. Only 11.7% (38) of the reviews focused specifically on primary, middle, or secondary school. The reviews that included multiple education levels frequently did not explore education level as an effect modifier. Thirty-nine reviews (12.0%) did not report the education level of participants in the included studies or use educational level as a criterion for including studies in the review. Most of the included reviews (262; 80.4%) did not report the ages of participants in included studies or the ages corresponding to the included education levels.\n\nMany of the reviews (112; 34.4%) included studies in multiple school subjects, often without exploring the subject as a potential effect modifier ( Table 3). Nearly one third (100; 30.7%) of the reviews focused on math and science topics. Many of the reviews (92; 28.2%) did not report the subjects that were the focus of the included studies.\n\n* STEM includes science, technology, engineering, and mathematics.\n\nThe included reviews addressed a wide range of teaching strategies, often using different terms to describe similar strategies, and using different definitions.70 We grouped the teaching strategies into 11 broad categories ( Table 4). Altogether, 110 reviews (33.7%) addressed the use of information and communication technology in education (“E-learning”). Half (55) of those reviews fit in a different category than E-learning category. For example, we included digital games in the category “games and role play”.\n\nTwenty-two reviews addressed the use of games or gamification, most of which focused on digital games, and we found 16 reviews of flipped classrooms ( Table 5). On the other hand, we found only four reviews of teacher training that reported student outcomes, and only eight reviews of the effects of different approaches to questioning and prompting students.\n\nThe included reviews reported a wide range of measures of academic achievement (measured using standardized tests or grades) or learning (measured using researcher- or teacher-created tests). Twenty-six reviews (8.0%) reported a measure of transfer. Forty-six reviews (14.1%) reported a measure of higher order thinking, including critical thinking (11 reviews; 3.4%), problem solving (16; 4.9%), metacognition (8; 2.5%), and argumentation (5; 1.5%).\n\nThree reviews mentioned adverse effects. One noted parenthetically in the authors’ conclusions that “We found … (and no significant adverse effects).” It did not refer to adverse effects anywhere else in the review. The other two reviews mentioned potential adverse effects (of parental involvement with homework, and of home environments). Two reviews mentioned practical disadvantages (student unfamiliarity and instructor start-up cost; and taking time away from instruction and students’ responses). Two reviews considered costs. Thirty-three reviews (10.1%) considered negative effects on the learning outcomes that were reported. The rest of the reviews (286; 87.7%) did not consider adverse effects, disadvantages, or costs.\n\nThe study designs included in the reviews often were not clear ( Table 6). Reviews frequently included “Experimental” and “quasi-experimental” studies without providing clear definitions. In some reviews, “experimental” clearly referred to studies using random allocation, but that was not always clear. “Quasi-experimental” could refer to a variety of different study designs. Similarly, when “quantitative” or “comparative” studies were included, the designs of the included studies often were not described.\n\n* “Experimental” and “quasi-experimental” were not well defined. Experimental studies sometimes clearly referred to randomized studies. Quasi-experimental studies may include a variety of study designs.\n\n† “Quantitative” or “comparative” studies may include a variety of study designs and may or may not include randomized trials.\n\nTwenty-four (7.4%) of the reviews assessed the risk of bias for included studies using explicit criteria. Twenty (6.1%) assessed “study quality” using explicit criteria, some of which are not directly related to the risk of bias, and four reviews (1.2%) did not clearly report the criteria that were used. Fifty-three reviews (20.2%) did not assess the risk of bias but included random allocation (53) or study design (13) as a potential effect moderator. The other 212 (65%) of the reviews did not address the risk of bias.\n\nMost reviews (235; 72.1%) assessed potential effect moderators using univariate meta-regressions (173 reviews; 53.1%), multivariate meta-regression (25; 7.7%), or network meta-analysis (1 review). Thirty-six reviews (11.0%) reported effects for subgroups of included studies without a test of interaction (statistical significance of differences between subgroups). Of the 235 reviews that assessed potential effect modifiers, 39 (16.2%) addressed limitations of those analyses due to, for example, a lack of data (17 reviews), general limitations of moderator analyses (10 reviews), or potential confounding (7 reviews). None of the included reviews systematically assessed the credibility of reported subgroup effects.\n\nWe prepared plain language summaries for 37 teaching strategies that we judged to be most relevant to teaching critical thinking in primary and secondary schools, and one for teacher training.70 These summaries informed the choice of teaching strategies that we used in Be Smart about your Health. We included teaching strategies that could potentially be used to teach critical thinking, even though we did not find a systematic review that directly considered effects on critical thinking. We also included strategies that are relevant for learning new vocabulary (such as important new terms that are introduced in the resources) and for explaining and helping students to understand the key concepts that are taught in the resources.\n\nFor each summary we included when the review authors last searched for evidence. We also included a judgement about the certainty of the evidence, based on limitations of the included studies (our assessment based on information provided in the reviews), imprecision of the effect estimates, and inconsistency of results. We judged the certainty of the evidence to be moderate for 16 teaching strategies, low to moderate for one, low for 11, and very low for 10 ( Table 7). We did not judge the certainty of the evidence to by high for any of the teaching strategies.\n\nWe categorised the size of the effects from little or no effect to a large effect, as shown in Table 7. The 122 average effect sizes that we included in the summaries ranged from 0.01 to 1.68, median 0.42 ( Figure 3). We wrote short descriptions and “bottom-line statements” for the teaching strategies that we considered most relevant. The bottom-line statements are shown in Table 8. The bottom-line statements communicate the certainty of the evidence and the size of the effects (when these were available). We constructed them by adapting strategies for writing informative sentences to communicate evidence from systematic reviews.47\n\n\n\n• Signalling\n\n\n\n• Integrated pictures and words\n\n\n\n• Verbal redundancy\n\n\n\n• Pedagogical agents\n\n\n\n• Cues, questions, and advance organizers\n\n\n\n• Asking high-level questions\n\n\n\n• Explanation prompts\n\n\n\n• Response cards\n\n\n\n• Similarities and differences\n\n\n\n• Setting objectives and providing feedback\n\n\n\n• Reinforcing effort and providing recognition\n\n\n\n• Computer-based assessment and feedback\n\n\n\n• Digital badges\n\n\n\n• Practice tests\n\n\n\n• Self-grading and peer-grading\n\n\n\n• Note taking and summarising\n\n\n\n• Non-linguistic representations\n\n\n\n• Homework and practice\n\n\n\n• Computer-based scaffolding for reading comprehension\n\n\n\n• Computer-based personalised instruction\n\n\n\n• Adaptation to students’ needs (differentiation)\n\n\n\n• Constructive and interactive activities\n\n\n\n• Cooperative learning\n\n\n\n• Small group discussion\n\n\n\n• Teacher guidance during collaborative learning\n\n\n\n• Computer-supported collaborative learning\n\n\n\n• Concept cartoons\n\n\n\n• Digital games\n\n\n\n• Role play\n\n\n\n• Active learning\n\n\n\n• Concept mapping\n\n\n\n• Applying knowledge to new problems\n\n\n\n• Inquiry-based instruction\n\n\n\n• Student question-based inquiry\n\n\n\n• Problem-based learning\n\n\n\n• Scaffolding for inquiry-based learning\n\n* References can be found in Oxman (2024).70\n\nAlthough many of the reviews had important limitations, they provided a valuable starting point for selecting and implementing teaching strategies that we incorporated in our educational resources and that teachers potentially can use to teach critical thinking. Some teaching strategies require more training and experience of teachers than others. We included information about the need for teacher training or experience, whenever this was addressed in a review.\n\n\nDiscussion\n\nHundreds of systematic reviews of teaching strategies have been produced over the past 20 years. They provide a valuable basis for informing decisions about the use of these strategies. However, these reviews have some important limitations, including:\n\n• Inconsistent terminology and definitions\n\n• Unnecessary duplication of efforts\n\n• Failure to consider adverse effects\n\n• Inadequate assessments of the risk of bias\n\n• Inadequate assessments of the credibility of subgroup effects (effect moderators)\n\nWe developed and revised a framework for categorising teaching strategies that met our needs. It is uncertain whether that framework will prove useful to others. Some of the reviews included in our overview could be classified in more than one way. Nonetheless, we found the framework helpful for organising the reviews and the teaching strategies and making sense of what is known. It would be helpful for users of this research if researchers studying the effects of teaching strategies could reach a consensus on a taxonomy. Similarly, it would be helpful if agreement could be reached on the terminology that is used to characterize outcome measures. Coordination by an organisation such as the Campbell Collaboration might help to reduce unnecessary duplication of efforts and make it easier to update the reviews. It might also help reduce the risk of bias in systematic reviews of teaching strategies.48\n\nOnly three of the systematic reviews included in this overview even mentioned adverse effects. Researchers commonly fail to consider potential adverse effects of educational and public health interventions.49–52 An adverse effect on an intended outcome is sometimes found, but other types of adverse effects are rarely considered, including misunderstanding, misapplication of learning, distrust, cognitive dissonance, stress, inequities, conflict, and wasted time or resources.\n\nMany of the systematic reviews did not assess the risk of bias for studies included in the reviews using explicit criteria. This made it difficult to judge the certainty of the evidence, i.e., confidence in the reported effect estimates.53–55 In addition, none of the reviews systematically assessed the credibility of reported subgroup (moderator) effects.56–58 The credibility of most subgroup claims in randomized trials, even strong claims, is usually low.59,60\n\nAlthough we have included effect sizes in our summaries of strategies that we considered most relevant to teaching critical thinking in primary and secondary schools, the average effect sizes summarised in Figure 3, as well as those reported in other overviews such as Hattie’s,61 are difficult to interpret for several reasons in addition to those noted above, including:\n\n• Variable quality of the included meta-analyses\n\n• Variable quality of the studies included in the meta-analyses62\n\n• Variable outcome measures\n\n• Variation in what each strategy was compared to\n\n• Variable statistical methods\n\n• General challenges to interpreting effect sizes63\n\nFor these reasons, the reported effect sizes should not be used to compare the effectiveness of different teaching strategies and firm conclusions cannot be drawn about the magnitude of effects for most of the teaching strategies.\n\nNonetheless, the findings of the systematic reviews that we considered most relevant for teaching critical thinking in primary and secondary schools helped to inform the design of the Be Smart about your Health resources. Because we developed the resources in East Africa, many of the teaching strategies that we considered potentially relevant in other settings were not practical in low-resource settings, particularly ones that depend on the availability of digital technology. We initially pilot tested resources that used different teaching strategies for each lesson. However, this was inefficient, since the strategies were new to both teachers and students, and this distracted from the learning goals of the lessons. Therefore, we selected a small number of strategies that we used consistently across lessons and only varied the main lesson strategy a few times ( Table 9).1\n\n\n\n• Guided notetaking\n\n• Small-group work\n\n• Response cards\n\n• Homework – collecting claims and choices about health actions\n\n• Standard lesson structure\n\n• Setting objectives and providing feedback\n\n• Multimedia design\n\n\n\n• Concept mapping\n\n• Concept cartoons\n\n• Inquiry-based instruction\n\n• Quizzes\n\n• Role play\n\nThe Be Smart about your Health intervention is being evaluated in randomized trials and process evaluations in Kenya, Rwanda, and Uganda.64–69\n\nLimitations of this overview and our findings include:\n\n• The searches were limited to two databases (Education Research Complete (EBSCO) and Education Resources Information Center (ERIC).\n\n• Coding the included reviews was challenging and there were frequent disagreements.\n\n• We did not systematically assess the risk of bias for included reviews.\n\n• The assessments of the certainty of the evidence for reported effects were based on information provided in the included reviews, which was frequently incomplete.\n\n• We did not assess the relevance of the reviews identified by the updated search or summarise the findings for any of those reviews.\n\nA coordinated effort by educational researchers and education professionals is needed to:\n\n• Reach a consensus on terminology and definitions of teaching strategies,\n\n• Set priorities for systematic reviews of teaching strategies for which a high quality, up-to-date systematic review cannot be found, and\n\n• Reduce unnecessary duplication of efforts.\n\nInvestigators preparing prioritised systematic reviews should consider the limitations that we identified in the included reviews when preparing a protocol. They should consider potential adverse effects, systematically assess the risk of bias for included studies, and systematically assess the credibility of subgroup effects (effect modifiers).\n\nTeachers and developers of educational resources for teaching critical thinking in primary and secondary schools may want to consider using some of the teaching strategies that we have judged to be most relevant. There are important uncertainties about the effects of most of those teaching strategies, and there may be other teaching strategies worth considering for which we did not find a systematic review. Nonetheless, the teaching strategies summarised provide a useful starting point for identifying and selecting potentially useful teaching strategies.70\n\n\nConclusions\n\nA tremendous amount of work has gone into evaluating the effects of a wide range of teaching strategies. The results of this research can inform decisions about how to teach critical thinking or achieve other learning goals, as well as decisions about further research to evaluate the effects of teaching strategies. However, well-designed, up-to-date systematic reviews are still needed for many teaching strategies. Coordination of efforts could help to address this need.\n\nEthics and consent were not required.",
"appendix": "Data availability\n\nZenodo: Dataset for “The effects of teaching strategies on learning to think critically in primary and secondary schools: an overview of systematic reviews”, https://doi.org/10.5281/zenodo.14001300.70\n\nThis project contains the following underlying data:\n\n- Included systematic reviews.xlsx\n\n- Overview of teaching strategies.xlsx\n\nZenodo: Dataset for “The effects of teaching strategies on learning to think critically in primary and secondary schools: an overview of systematic reviews”, https://doi.org/10.5281/zenodo.14001300.70\n\nThis project contains the following extended data:\n\n- Education Research Complete search strategy.docx\n\n- ERIC search strategy.docx\n\n- PRISMA_2020_checklist teaching strategies.docx\n\n- Strategies for teaching critical thinking.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe would like to thank Astrid Dahlgren and Nelson Sewankambo for their contributions to the protocol; Marit Johansen for developing the search strategies; Iain Chalmers, Steven Higgins, Monica Melby-Lervåg, and Matt Oxman for providing feedback on the protocol; and Monica Melby-Lervåg and Jonathan Sharples for providing feedback on an earlier version of this manuscript.\n\n\nReferences\n\nRosenbaum SE, Moberg J, Chesire F, et al.: Teaching critical thinking about health information and choices in secondary schools: human-centred design of digital resources. F1000Res. 2023; 12: 481. Publisher Full Text\n\nChesire F, Ochieng M, Mugisha M, et al.: Contextualizing critical thinking about health using digital technology in secondary schools in Kenya: a qualitative analysis. Pilot Feasibility Stud. 2022; 8(1): 227. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMugisha M, Uwitonze AM, Chesire F, et al.: Teaching critical thinking about health using digital technology in lower secondary schools in Rwanda: A qualitative context analysis. PLoS One. 2021; 16(3): e0248773. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSsenyonga R, Sewankambo NK, Mugagga SK, et al.: Learning to think critically about health using digital technology in Ugandan lower secondary schools: a contextual analysis. PLoS One. 2022; 17(2): e0260367. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAronson JK, Barends E, Boruch R, et al.: Key concepts for making informed choices. Nature. 2019; 572(7769): 303–306. Publisher Full Text\n\nAgaba JJ, Chesire F, Mugisha M, et al.: Prioritisation of Informed Health Choices (IHC) Key Concepts to be included in lower-secondary school resources: a consensus study. PLoS One. 2023; 18(4): e0267422. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOxman AD, Chalmers I, Dahlgren A: Key Concepts for Informed Health Choices: Where’s the evidence?. F1000Res. 2023; 11: 890. Publisher Full Text\n\nVoogt J, Roblin NP: A comparative analysis of international frameworks for 21st century competences: Implications for national curriculum policies. J. Curric. Stud. 2012; 44(3): 299–321. Publisher Full Text\n\nPresseisen BZ: Critical thinking and thinking skills: State of the art definitions and practice in public schools. Annual Meeting of the American Educational Research Association. San Francisco, CA: Research for Better Schools; 1986. Reference Source\n\nFollman J: Critical thinking definitions. Inquiry. 1991; 8(2): 4–5. Publisher Full Text\n\nMoseley D, Baumfield V, Elliott J, et al.: Frameworks for Thinking: A Handbook for Teaching and Learning. Cambridge University Press; 2005. Publisher Full Text\n\nMoore T: Critical thinking: Seven definitions in search of a concept. Stud. High. Educ. 2013; 38(4): 506–522. Publisher Full Text\n\nGyenes A: Definitions of critical thinking in context. Ann. Educ. Stud. 2015; 20: 17–25. Publisher Full Text\n\nEnnis R: Critical thinking: Reflection and perspective Part I. Inquiry. 2011; 26(2): 4–18. Publisher Full Text\n\nPolanin JR, Maynard BR, Dell NA: Overviews in education research: A systematic review and analysis. Rev. Educ. Res. 2017; 87(1): 172–203. Publisher Full Text\n\nSloman SA, Fernbach P: The Knowledge Illusion: Why We Never Think Alone. New York: Penguin; 2017.\n\nBaron J: Thinking and Deciding. 4th ed.Cambridge, UK: Cambridge University Press; 2008.\n\nKillen R: Effective Teaching Strategies: Lessons from Research and Practice. 7th ed.South Melbourne, Victoria: Cengage Learning Australia; 2016.\n\nBeck CR: A taxonomy for identifying, classifying, and interrelating teaching strategies. J. Gen. Educ. 1998; 47(1): 37–62. Reference Source\n\nDorgu TE: Different teaching methods: a panacea for effective curriculum implementation in the classroom. Int. J. Secondary Educ. 2015; 3(6): 77–87. Publisher Full Text\n\nEl Soufi N, See BH: Does explicit teaching of critical thinking improve critical thinking skills of English language learners in higher education? A critical review of causal evidence. Stud. Educ. Eval. 2019; 60: 140–162. Publisher Full Text\n\nCaro DH, Lenkeit J, Kyriakides L: Teaching strategies and differential effectiveness across learning contexts: Evidence from PISA 2012. Stud. Educ. Eval. 2016; 49: 30–41. Publisher Full Text\n\nAlberta Learning: Instructional strategies. Health and Life Skills Guide to Implementation (K-9). Edmonton, ALB: Alberta Learning; 2002. Reference Source\n\nPomerance L, Greenberg J, Walsh K: Learning about Learning: What Every New Teacher Needs to Know. Washington, DC: National Council on Teacher Quality; 2016. Reference Source\n\nAbrami PC, Bernard RM, Borokhovski E, et al.: Strategies for teaching students to think critically: a meta-analysis. Rev. Educ. Res. 2015; 85(2): 275–314. Publisher Full Text\n\nÇeviker Ay Ş, Orhan A: The effect of different critical thinking teaching approaches on critical thinking skills: a meta-analysis study. Pamukkale Univ. J. Educ. 2020; 49: 88–111. Publisher Full Text\n\nBangert-Drowns RL, Bankert E: Meta-Analysis of Effects of Explicit Instruction for Critical Thinking. Annual Meeting of the American Educational Research Association. Boston, MA: 1990. Reference Source\n\nDiPasquale J, Hunter W: Critical thinking in asynchronous online discussions: a systematic review. Can. J. Learn. Technol. 2017; 43(2). Reference Source\n\nNurul Syazwani I, Jamalludin H, Shaharuddin MS, et al.: Supporting students’ critical thinking with a mobile learning environment: a meta-analysis. Proceedings of INTED2016 Conference. Valencia, Spain: 2016; pp. 3746–3755. Reference Source\n\nKarabulut US: Identifying instructional methods of teaching critical thinking: A systematic review and analysis of three decades of literature. Georgia Soc. Stud. J. 2015; 5: 96–107. Reference Source\n\nLorencová H, Jarošová E, Avgitidou S, et al.: Critical thinking practices in teacher education programmes: a systematic review. Stud. High. Educ. 2019; 44(5): 844–859. Publisher Full Text\n\nNgudgratoke S: A meta-analysis of relationships between teaching methods and critical thinking. 61st World Assembly ICET Re-thinking Teacher Professional Education: Using Research Findings for Better Learning. Brno, Czechia: Masaryk University; 2018; pp. 258–267. Reference Source\n\nNiu L, Behar-Horenstein LS, Garvan CW: Do instructional interventions influence college students’ critical thinking skills? A meta-analysis. Educ Res Rev. 2013; 9: 114–128. Publisher Full Text\n\nPuig B, Blanco-Anaya P, Bargiela IM, et al.: A systematic review on critical thinking intervention studies in higher education across professional fields. Stud. High. Educ. 2019; 44(5): 860–869. Publisher Full Text\n\nten Dam G , Volman M: Critical thinking as a citizenship competence: teaching strategies. Learn. Instr. 2004; 14(4): 359–379. Publisher Full Text\n\nTiruneh DT, Verburgh A, Elen J: Effectiveness of critical thinking instruction in higher education: a systematic review of intervention studies. High. Educ. Stud. 2014; 4(1): 1–17. Publisher Full Text\n\nDewey J: The educational significance of concepts. How We Think: A Restatement of the Relation of Reflective Thinking to the Educative Process. 2nd ed.Boston: DC Heath and Company; 1933; pp. 153–154.\n\nOxman AD, Dahlgren A, Garcia Marti S, et al.: The effects of teaching strategies on learning to think critically in primary and secondary schools: protocol for an overview of systematic reviews. IHC Working Paper. 2019. Publisher Full Text\n\nDoyle W: Academic work. Rev. Educ. Res. 1983; 53(2): 159–199. Publisher Full Text\n\nBloom BS, Engelhart MD, Furst EJ, et al.: Taxonomy of educational objectives: The classification of educational goals. Bloom BS, editor. London: Longmans; 1956. Reference Source\n\nPashler H, Bain PM, Bottge BA, et al.: Organizing instruction and study to improve student learning. IES Practice Guide. 2007. NCER 2007-2004. Reference Source\n\nCochrane Response: About us.Reference Source\n\nWard DJ, Furber C, Tierney S, et al.: Using Framework Analysis in nursing research: a worked example. J. Adv. Nurs. 2013; 69(11): 2423–2431. Publisher Full Text\n\nBrunton G, Oliver S, Thomas J: Innovations in framework synthesis as a systematic review method. Res. Synth. Methods. 2020; 11(3): 316–330. Publisher Full Text\n\nGuyatt GH, Oxman AD, Kunz R, et al.: What is “quality of evidence” and why is it important to clinicians? BMJ. 2008; 336(7651): 995–998. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBalshem H, Helfand M, Schunemann HJ, et al.: GRADE guidelines: 3. Rating the quality of evidence. J. Clin. Epidemiol. 2011; 64(4): 401–406. Publisher Full Text\n\nSantesso N, Glenton C, Dahm P, et al.: GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions. J. Clin. Epidemiol. 2020; 119: 126–135. PubMed Abstract | Publisher Full Text\n\nWhiting P, Savović J, Higgins JP, et al.: ROBIS: A new tool to assess risk of bias in systematic reviews was developed. J. Clin. Epidemiol. 2016; 69: 225–234. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao Y: What works may hurt: Side effects in education. J. Educ. Chang. 2017; 18(1): 1–19. Publisher Full Text\n\nLorenc T, Oliver K: Adverse effects of public health interventions: a conceptual framework. J. Epidemiol. Community Health. 2014; 68(3): 288–290. PubMed Abstract | Publisher Full Text\n\nBonell C, Jamal F, Melendez-Torres GJ, et al.: ‘Dark logic’: theorising the harmful consequences of public health interventions. J. Epidemiol. Community Health. 2015; 69(1): 95–98. PubMed Abstract | Publisher Full Text\n\nOxman M, Chesire F, Mugisha M, et al.: Potential adverse effects of an educational intervention: Development of a framework. Glob Health Sci Pract. 2024; submitted. Publisher Full Text\n\nSterne JA, Hernán MA, Reeves BC, et al.: ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSterne JAC, Savović J, Page MJ, et al.: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898. Publisher Full Text\n\nGuyatt GH, Oxman AD, Vist G, et al.: GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). J. Clin. Epidemiol. 2011; 64(4): 407–415. PubMed Abstract | Publisher Full Text\n\nSchandelmaier S, Briel M, Varadhan R, et al.: Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses. CMAJ. 2020; 192(32): E901–E906. Publisher Full Text\n\nSun X, Ioannidis JP, Agoritsas T, et al.: How to use a subgroup analysis: users’ guide to the medical literature. JAMA. 2014; 311(4): 405–411. Publisher Full Text\n\nOxman AD: Subgroup analyses. BMJ. 2012; 344: e2022. Publisher Full Text\n\nSun X, Briel M, Busse JW, et al.: Credibility of claims of subgroup effects in randomised controlled trials: systematic review. BMJ. 2012; 344: e1553. PubMed Abstract | Publisher Full Text\n\nRichardson M, Garner P, Donegan S: Interpretation of subgroup analyses in systematic reviews: a tutorial. Clin. Epidemiol. Glob. Health. 2019; 7(2): 192–198. Publisher Full Text\n\nHattie J: Visible learning for teachers: Maximizing impact on learning. Oxon, England: Routledge; 2012. Reference Source\n\nSlavin R: Robert Slavin’s Blog 2018.December 5, 2022. Reference Source\n\nGuyatt GH, Thorlund K, Oxman AD, et al.: GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes. J. Clin. Epidemiol. 2013; 66(2): 173–183. PubMed Abstract | Publisher Full Text\n\nChesire F, Kaseje M, Ochieng M, et al.: Effects of the Informed Health Choices secondary school intervention on the ability of lower secondary students in Kenya to think critically about health information and choices: Protocol for a cluster-randomized trial. IHC Working Paper. 2022. Publisher Full Text\n\nMugisha M, Nyirazinyoye L, Simbi CMC, et al.: Effects of Informed Health Choices secondary school resources on the ability of Rwandan students to think critically about health: protocol for a cluster-randomised trial. IHC Working Paper. 2022. Publisher Full Text\n\nSsenyonga R, Oxman AD, Nakyejwe E, et al.: Does the use of the Informed Health Choices secondary school resources improve critical thinking about the effects of health among secondary school students in Uganda? A cluster-randomised trial protocol. IHC Working Paper. 2022. Publisher Full Text\n\nChesire F, Kaseje M, Ochieng M, et al.: Effect of the Informed Health Choices digital secondary school resources on the ability of lower secondary students in Kenya to critically appraise health claims: protocol for a process evaluation. IHC Working Paper. 2022. Publisher Full Text\n\nMugisha M, Nyirazinyoye L, Oxman AD, et al.: Use of the Informed Health Choices digital resources for teaching lower secondary school students in Rwanda to think critically about health: protocol for a process evaluation. IHC Working Paper. 2022. Publisher Full Text\n\nSsenyonga R, Lewin S, Nakyejwe E, et al.: Informed heath choices intervention to teach secondary school adolescents in Uganda to assess claims about treatment effects: a process evaluation protocol. IHC Working Paper. 2022. Publisher Full Text\n\nMunthe-Kaas HM: Dataset for “The effects of teaching strategies on learning to think critically in primary and secondary schools: an overview of systematic reviews”. [Data set]. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "345795",
"date": "28 Jan 2025",
"name": "Sofia Avgitidou",
"expertise": [
"Reviewer Expertise Initial and in-service teacher education",
"professional learning",
"transformation of education and educational change",
"democratic and participatory education"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis an interesting paper with clear objectives and criteria for a systematic review of other reviews on teaching strategies and their effects on learning and critical thinking in education. Despite the lack of some evidence in the reviews that were anaysed, the study contributes to the categorisation of teaching strategies and in summarizing their (possible) effects on learning.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1426
|
https://f1000research.com/articles/13-858/v1
|
01 Aug 24
|
{
"type": "Study Protocol",
"title": "Protocol for the systematic review of age and sex in preclinical models of age-correlated diseases",
"authors": [
"Kai Diederich",
"Matthias Steinfath",
"Alexandra Bannach-Brown",
"Bettina Bert",
"Daniel Butzke",
"Paul Lucas Wildner",
"Maximilian Wurm",
"Ines Schadock",
"Céline Heinl",
"Kai Diederich",
"Matthias Steinfath",
"Alexandra Bannach-Brown",
"Bettina Bert",
"Daniel Butzke",
"Paul Lucas Wildner",
"Maximilian Wurm",
"Ines Schadock"
],
"abstract": "The translation of animal-based biomedical research into clinical research is often inadequate. Maximizing translation should be central to animal research on human diseases, guiding researchers in study design and animal model selection. However, practical considerations often drive the choice of animal model, which may not always reflect key patient characteristics, such as sex and age, impacting the disease's course. Despite diseases affecting both sexes, researchers frequently use male mice. To address this imbalance, journals and funding agencies have begun questioning the sex of animals used in studies and issued new guidelines. Conversely, the age of rodents is rarely discussed, even though many diseases primarily affect older patients. Young mice are commonly used, even in studies of diseases affecting older adults. Systematic comparisons between the age of rodents used and the age of patients in clinical trials are lacking. In this review, we systematically analyze the age and sex of mice used to model the five leading causes of global disability-adjusted life-years over the age of 75. We compare the results with the age and sex of patients in clinical trials focusing on Alzheimer's disease, stroke, type 2 diabetes mellitus, ischemic heart disease, and chronic obstructive pulmonary disease. We also analyze whether the age of the mice used has changed over the past decade. By systematically assessing the age and sex of the mice, we aim to initiate a discussion on the appropriate choice of animal model to improve the translatability of research results.",
"keywords": [
"systematic review",
"experimental animals",
"age",
"sex",
"translation"
],
"content": "Introduction\n\nAnimal research is primarily concerned with the study of human diseases and the search for potential treatments.1 As the translation of basic research to humans is its main purpose, we would assume that maximizing the translational value of the results for patients should be central. Successful translation requires the validity of preclinical studies, both internal and external. Internal validity refers to experimental reproducibility, and external validity refers to the generalizability of results beyond a single research study. The external validity of preclinical studies is key for reflecting factors important for clinical translation, such as sex, age, and immune status.2 Therefore, biological factors such as sex and age of the patients should be considered when choosing the experimental animal model, as they may influence the onset and course of a disease. However, sex is still not adequately represented in animal models of disease.3 Until recently, it was assumed that the inclusion of female animals was not relevant in studies beyond the reproductive system and that the estrous cycle would add more unwanted variability.4 This misconception has led to a preference for male mammals in many areas of research.5 This concept has been refuted by evidence that sex affects most phenotypic traits in mice and that including both sexes lead to more robust and generalizable results.6–8 Key players in the research system have since attempted to correct this imbalance by issuing new guidelines.9,10 Funders such as the National Institutes of Health (NIH) now require researchers to justify using only one sex. In addition, several biomedical journals have adopted the Sex And Gender Equity in Research (SAGER) guidelines in their editorial policies, which require similar explanations.11,12 An initial evaluation ten years after the introduction of these measures revealed a change toward a reduction in sex bias.3 However, this improvement has not been uniform across all research fields. In neuroscience, for example, there was a large increase in studies involving both sexes, whereas in pharmacology, no change was observed.3\n\nAn additional, but less discussed, biological factor is the representation of age in experimental animal models. Indeed, many diseases are age-related, and the age of patients plays an important role in the development and course of the disease.13 However, the choice of rodent age may not always reflect the age of patients. In fact, a survey of nearly 300 researchers from different fields identified practical factors such as cost, animal supply or comparability with historical data as key factors. In this survey, the age of the rodents used, as reported by the respondents, clustered approximately 8-12 weeks for both mice and rats, regardless of the disease model being studied.14 An age of 8-12 weeks in rodents corresponds to a young adult in humans.15 Whether this age bias is observed in the broader scientific literature and whether it remains constant over time remain to be demonstrated.\n\nIn our planned systematic review, we will systematically assess the age and sex of mice in studies that focus on age-related diseases. We focus on mice because they are the most commonly used species in basic research on human diseases. We selected research areas according to the most recent assessment of the global burden of disease in 2019, published in 2020.16 Thus, we will consider studies on the five leading causes of global disability-adjusted life years over the age of 75, namely, Alzheimer's disease, stroke, diabetes mellitus type 2, ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD). As the last decade has been marked by extensive discussions on the reproducibility and translation of animal research, we will also assess whether the age of the mice used has changed in the last 10 years. Clinical trials are also characterized by an age bias toward younger patients compared to the general patient population. Therefore, we will also assess the age of patients enrolled in clinical trials for the five diseases studied for comparison with preclinical studies.17\n\n\nMethods\n\nWe designed the study using the SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation's) protocol template developed for systematic reviews of animal studies and the PRISMA-P checklist.18,19 This protocol was registered at PROSPERO (CRD42023481414). To date, we have completed preliminary searches, conducted pilot studies to inform our statistical planning, tested our extraction process and started abstract screening.\n\nWhat is the age and sex of mice versus humans in published research of the age-correlated diseases: Alzheimer’s disease, stroke, diabetes mellitus type 2, IHD and chronic obstructive pulmonary disease? Our research question was based on the PICo scheme: Population (mice and humans), phenomenon of Interest (age and sex) and Context (age-correlated diseases).20 We will further investigate whether the age and sex of the mice used in these mouse models have changed in the last ten years.\n\nWe defined different sets of inclusion and exclusion criteria for preclinical and clinical studies. For the preclinical literature, beyond the age and sex of the mice used, we will extract additional data, such as the animal model of the disease and the risk of bias. By sampling these data from the years 2023 and 2013, we want to evaluate the current state of the preclinical literature of the different fields and potentially detect a change in these factors within the last ten years. In contrast, for clinical studies, we only want to obtain an estimate of the age and sex of patients participating in clinical trials of specific diseases to make a narrative comparison to the age and sex of the animals. Based on these two main aims, we defined two different sets of eligibility criteria:\n\nPreclinical research\n\nWe will include all studies designed to primarily investigate Alzheimer’s disease, stroke, diabetes mellitus type 2, IHD or COPD, independent of their study design. We will exclude studies that focus on other diseases.\n\nWe will only include studies using mice (genus Mus) in vivo or ex vivo to investigate one of the five considered diseases. Since it is not possible to translate and combine the ages of different animal species in a reasonable way, we decided to focus on mice, the most frequently used animal model.21 Studies using other animals or cell lines will be excluded.\n\nStudies will be included independently of the assessed outcome. However, studies that do not report the age of the mice will be excluded from the data analysis of age during full-text screening. In the second step, an excluded study due to missing age reporting will be replaced by another study to reach the predefined number of articles (Figure 3).\n\nWe will only consider original articles and exclude abstract-only publications and reviews. To assess whether we see a change in the published literature within the last ten years, we will only use studies published either in 2013 or in 2023.\n\nWe will include studies in all languages with help from international collaborators and automated translation software.\n\nClinical research\n\nWe will use the Cochrane Library for the assessment of the age of patients included in the clinical trials. We selected Cochrane reviews because the authors extracted the age and sex of the included patients from the original trial reports that were retrieved upon systematic searches of different databases. We will only include Cochrane reviews that included studies with patients with one of the five investigated diseases. Only reviews including studies performed on healthy volunteers will be excluded.\n\nReviews will be included independently of the assessed outcome. However, if the entire Cochrane review does not report the age of the patients, this review will be excluded during full text screening and will be replaced by another review to reach the predefined number of articles. If only individual trials listed in a Cochrane review do not report age, the entire review will still be included.\n\nWe will only consider studies listed in Cochrane reviews. We will not exclude any publication year since the year of the clinical trials varies in any case within the Cochrane review, and we are not planning to analyze changes in the age or sex of patients over time. All the Cochrane reviews are all written in English; therefore, no language restrictions apply.\n\nBased on our different eligibility criteria for preclinical and clinical research, we will use different databases and bibliographic search strategies for preclinical and clinical studies.\n\nPreclinical research\n\nFor the screening of the literature on research performed on mice, we will use Medline via PubMed® via and Embase via Ovid. Our search string will consist of medical subject headings (MeSH terms) for PubMed® and Emtree for Embase as well as keyword entries combined with Boolean operators. Our search string combines terms from four categories: animal, specific disease, year of publication and type of publication (see supporting information).\n\nClinical research\n\nFor the assessment of the age and sex of participants in clinical trials, we will use the Cochrane Library to search for eligible reviews. Since the database only includes reviews of human trials, we do not need to implement search strings for the species or the type of publication. We do not aim to analyze any change over time for the age of the patients and therefore do not restrain our search by publication date. Our search string therefore only includes synonyms for the specific diseases. We will use a combination of MeSH terms for the diseases as well as direct entries (see supporting information).\n\nSince the chosen diseases are research intensive, we are not aiming to provide a complete overview of the scientific literature of these fields. We rather want to get a valid estimate of the age and sex of the mice used and evaluate whether there has been a change in this regard in the last 10 years. Additionally, we are planning for a meaningful estimate of the age and sex of the patients included in clinical trials of the specified diseases to make a narrative comparison with the age of the rodents. To determine how many publications need to be screened for these two purposes, we performed two different pilot studies: one on the preclinical literature and one on the clinical literature.\n\nPilot study for preclinical literature screening\n\nThe aim of the pilot study was to estimate the mean and variability of the age of the mice used in the different research fields. With these results, we have determined the number of articles that have to be screened to evaluate a change in the age of the mice within the last ten years. We therefore randomly selected 20 articles per disease of interest that were published within the last ten years. For this purpose, we performed a rough search in PubMed® with the names of the disease and the term “mouse”. We then created 20 random numbers within this range of results. We always started with the random number and then took the first article that met our eligibility criteria described above. From these articles, we extracted the ages of the mice used (see data extraction). Based on these results, we calculated the number of studies required to detect a biologically meaningful change in the age of the animals in the last ten years with a power of 80 % (Supporting information). Since the median and the variability of the ages of the mice differ greatly among the different diseases, we defined different age changes to be detected in the different diseases. First, a change of two weeks is biologically more meaningful in adolescent mice than in geriatric mice, and second, the number of studies that can realistically be screened is also restricted by the limited number of collaborators. Although the ages of the mice in the IHD and stroke groups strongly clusters around ten weeks without any notable variability, the mice in the COPD and diabetes mellitus type 2 research are older, and the variability is higher (Figure 1). Research on Alzheimer’s disease seems to use the oldest mice and shows great variability. We therefore decided to aim for a detection of a difference of two weeks for IHD and stroke, three weeks for COPD and diabetes mellitus type 2 and eight weeks for Alzheimer’s disease (Table 1). Since it could be hypothesized that some studies used very young mice and some old mice, the age distribution in the different studies might be multimodal. We therefore tested for this heterogeneity but could not detect any polymodality (Supporting information). This procedure will also be applied in the main study.\n\nWhiskers denote the 10th and 90th percentiles, the central line represents the median, and o symbolizes outliers defined as more than 1.5 times the interquartile range.\n\nBased on the median age, variability, and work force, we decided on an age difference that we would consider biologically relevant. We then calculated the number of studies required to detect this difference with a power of at least 80% (Supporting information).\n\nPilot study for the clinical literature screen\n\nTo evaluate the age and sex of participants included in clinical trials, we will use a straightforward approach by using the extracted age and sex of patients from clinical trials that are listed in Cochrane reviews. In a pilot extraction, we assessed the median and the variability of the age of patients in clinical trials in a sample of five Cochrane reviews for three diseases each. We looked at Alzheimer’s disease and diabetes mellitus type 2, where we expected the strongest differences in age and variability and additionally included stroke as a third disease that we had anticipated to be between the other two. Indeed, whereas diabetes mellitus type 2 can occur at an earlier age, Alzheimer’s disease is mainly found in elderly patients. Accordingly, we found a median age of 54 years for patients with diabetes mellitus type 2, 72.65 years for patients with Alzheimer’s disease and 71.4 years for patients with stroke (Figure 2). We did not observe meaningful differences in the variability between these three diseases and anticipate similar results for COPD and IHD. The included Cochrane reviews included different numbers of trials, resulting in different sample sizes for each disease. Thus, the five Cochrane reviews resulted in 61 trials for diabetes mellitus type 2, 27 trials for stroke and 46 trials for Alzheimer’s disease.\n\nAlthough the median age varies between the diseases, the variability remains similar. Due to the variable number of trials per Cochrane review, each boxplot represents a different number of trials: Alzheimer’s disease: n = 46 (from 65 trials, 19 did not report the age of the patients); stroke: n = 27 (from 30 trials 3 did not report the age); diabetes mellitus type 2: n = 61 (from 123 trials 62 did not report the age). Whiskers denote the 10th and 90th percentiles, the central line represents the median, and o symbolizes outliers defined as more than 1.5 times the interquartile range.\n\nAfter assessing the variability in age within the trials included in one Cochrane review and between different reviews, we projected that analyzing ten Cochrane reviews for each considered disease would be precise enough to provide a valid estimate of the age of the patients included in clinical trials. In contrast to preclinical studies, we do not test for any change in time and therefore did not perform a power calculation. A detailed description of the method can be found in the supporting information.\n\nBased on our pilot studies, we calculated the number of articles to be screened in advance. To select the required studies, we will import all the retrieved citations from our search from PubMed®/Medline and EMBASE for each disease individually into EndNote™. After removal of duplicates, we will generate a set of random citations with EndNote™.22 We will use as many citations as predefined by our statistical planning plus an additional 25 % to account for dropouts for the full-text screening (Figure 3). Our pilot screening revealed that approximately 25% of the studies did not report the age of the mice. The citations will be imported into SYRF (RRID:SCR_018907) for formal abstract screening.23 If we do not reach the target number of articles after the full-text screening, we run the two screening phases again with an additional set of randomly selected citations.\n\nAfter retrieving all records and removing the duplicates, we will perform a random selection that will enter the screening phase. If, in the end, we do not reach the predefined number of required articles, we will fill this gap with a new random selection of studies.\n\nSimilarly, for the clinical studies, we will import all the search results from the Cochrane Library into EndNote™. After removal of the duplicates, we will perform a random pick and replace drop-outs until we reach the predefined number of Cochrane reviews in the same manner as described for the preclinical literature.\n\nTwo independent reviewers, blinded to each other's scoring, will screen titles and abstracts against the inclusion and exclusion criteria. A third reviewer will resolve any discrepancies. Similarly, two independent reviewers, blinded to each other's assessments, will evaluate the full texts to determine final inclusion. If differences occur in the data extraction, a third reviewer will resolve divergences.\n\nWe will retrieve the following information from the animal studies: bibliographic details, animal model characteristics, reporting quality and study quality. For clinical trials, we will only retrieve bibliographic details and patient characteristics. Since the studies included in a Cochrane review might already have been selected based on the study quality, the studies used do not reflect the general quality of the clinical literature for these research fields and will therefore not be extracted.\n\nPreclinical studies\n\nWe will extract the title, year of publication, first and last names of the first and last authors, and country of the institution of the first and last authors. Furthermore, for all studies included, we will define the probable gender of the first and last authors by combining the first name and the country of the institution. By assessing the probable gender of the first and last authors, we will analyze whether the gender of the researchers affects sex bias in preclinical and clinical studies. Indeed, a recently published study indicated that sex-related questions are more likely to be studied if the first or the last author of a publication is female.24 However, whether this effect also affects the sex of the mice used in this research remains unknown. We will use the Gender API (https://gender-api.com/de) for an automatic assessment of authors’ probable gender. The API provides an accuracy score for each first name in combination with the country of the institution where the study is performed.\n\nClinical studies\n\nFor the human studies, we will retrieve the title, the year of publication and the name of the authors and the country of the institution from the last author of the Cochrane reviews, as well as for the included original studies.\n\nPreclinical studies\n\nWe will extract the age of the mice at the first outcome measurement after disease induction. If an age range is given, we will use the mean between the minimum and the maximum age. If only weight is given, we will convert it into age in weeks using information provided by animal suppliers. If the age or weight is not reported, we will note this and use it as an indicator of reporting quality and extract all other information from the article. We will, however, add another article to reach the predefined number of articles for the calculation of the mean age of the mice used. If different age groups of mice are used in a study, we will extract the age of the oldest group.\n\nWe will further assess the sex of the mice used, the strain, the supplier and whether the animals are genetically modified. We will also extract the model of induction for the specific diseases and determine the presence of comorbidities.\n\nClinical studies\n\nFor the clinical trials, we will extract the mean age of all patients of the trial and the sex of the patients from the Cochrane review. We will not record the ages of the participants in the healthy control groups. We will further record the presence of comorbidities.\n\nPreclinical studies\n\nAs indicators of the reporting quality, we will evaluate whether all the animal model characteristics have been reported and how this reporting changed over time in the preclinical literature. We will differentiate whether age was given as weight, as a range with its extent or as exact age. We will note whether the sex was reported and if the exact number of animals for each sex is described. We will also assess the level of accessibility of the study. We will note whether the article was published open access and whether the data were shared and categorize this accessibility. We define open access as green, gray or gold open access. For the data sharing, we will differentiate between those available for download from the journals’ website or a repository, those available upon request, those for which data sharing is not applicable (e.g., “all data appear in the article” or “no datasets were generated or analyzed”) and those for which no data availability statement is available.\n\nClinical studies\n\nThe studies included in the Cochrane reviews do not reflect the general clinical literature, as they might be selected based on quality criteria. Hence, we refrain from extracting these data.\n\nPreclinical studies\n\nTo evaluate the study quality, we will use a modified version of the CAMARADES checklist for study quality.25 We will thus extract the reporting of random allocation, allocation concealment, blinded outcome assessment, sample size calculation, animal exclusions (including reasons and number of excluded animals), potential conflicts of interest, and compliance with animal welfare regulations. However, quality will not be used as an eligibility criterion.\n\nClinical studies\n\nSince the focus of our study is preclinical research, the quality of the clinical trials is out of scope and will not be further evaluated.\n\nPreclinical studies\n\nWe will synthesize the age in weeks for each research field and for each year. We will compare whether we can detect a change in age between the ages of the mice used in publications in 2013 and those used in 2023.\n\nClinical studies\n\nWe will synthesize the age of the patients enrolled in the clinical trials of the specific diseases. We are not planning to statistically compare the age of the mice versus the age of the patients; however, after calculating the mean ages, we will make a qualitative comparison.\n\n\nDiscussion\n\nThe translation of promising results from animal experiments in human patients is limited. There are multiple reasons for this unsatisfactory success rate.26 Not only biomedical research but also other disciplines are facing a major reproducibility crisis.27 The lack of reproducibility may be caused by factors unrelated to the biology of the model organisms, such as selective reporting of outcomes, poor statistical planning, and insufficient reporting.27,28 However, in addition to these general problems that may occur across research fields, the poor reflection of patient characteristics in animal models and other threats to external validity might play a critical role in translational failure.29 Our study cannot show any causal relationship between insufficient translation and the choice of animal model. However, we can identify and discuss discrepancies in biological characteristics between preclinical and clinical research.\n\nOur statistical planning, including the sample size calculation for preclinical studies, is entirely based on comparisons of the ages of mice between different years. This means that other analyses, e.g., the reporting quality or the sex of the animals, will be exploratory. Our approach to using Cochrane reviews has some limitations, as Cochrane reviews already have some eligibility criteria for the included trials that might affect the age and sex of the patients. However, these methods are straightforward for obtaining an estimate of the age of the patients included in clinical trials and might also be affected by age bias.30\n\nWe expect that with our systematic review, we can transparently show the extent of the age gap in preclinical biomedical research and initiate a broader discussion on the topic.\n\n\nEthics approval and consent to participate\n\nNot applicable\n\n\nConsent for publication\n\nNot applicable\n\n\nAuthors' contributions\n\nKD, AB-B, BB, and CH: developed the study concept and design. KD, MS, DB, PLW, MW, IS, and CH were involved in data acquisition and analysis. KD and CH: drafted the manuscript and figures. All authors contributed to the article and approved the submitted version.",
"appendix": "Data availability statement\n\nAll data associated with this article are available on the Open Science Framework (OSF).\n\nOSF: Systematic Review of Age and Sex in Preclinical Models of Age-Correlated Diseases. 31 https://osf.io/zma35/\n\n• Prisma-P flowchart of the eligibility of included preclinical studies\n\n• Prisma-P Checklist\n\n• Data sheet: clinical pilot data\n\n• Data sheet: preclinical pilot data\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOSF: Systematic Review of Age and Sex in Preclinical Models of Age-Correlated Diseases. 31 https://osf.io/zma35/\n\n• Supporting Information: search strings and evaluation of the pilot study for preclinical studies and sample size determination\n\nGithub: Systematic review of age and sex in preclinical models of age correlated-diseases 32 https://github.com/celinebf3r/Systematic-review-of-age-and-sex-in-preclinical-models-of-age-correlated-diseases\n\n• R-Code and data used and collected in the pilot study that served as the basis for the development of the study protocol\n\n• Data and code are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe thank CAMARADES for providing valuable advice on the design of our study.\n\n\nReferences\n\nBert B, Dörendahl A, Leich N, et al.: Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research. PLoS Biol. 2017; 15(12): e2003217. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDirnagl U, Duda GN, Grainger DW, et al.: Reproducibility, relevance and reliability as barriers to efficient and credible biomedical technology translation. Adv. Drug Deliv. Rev. 2022; 182: 114118. PubMed Abstract | Publisher Full Text\n\nWoitowich NC, Beery A, Woodruff T: A 10-year follow-up study of sex inclusion in the biological sciences. elife. 2020; 9: e56344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCahill L: A Half-Truth Is a Whole Lie: On the Necessity of Investigating Sex Influences on the Brain. Endocrinology. 2012; 153(6): 2541–2543. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeery AK, Zucker I: Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 2011; 35(3): 565–572. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPrendergast BJ, Onishi KG, Zucker I: Female mice liberated for inclusion in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 2014; 40: 1–5. PubMed Abstract | Publisher Full Text\n\nLevy DR, Hunter N, Lin S, et al.: Mouse spontaneous behavior reflects individual variation rather than estrous state. Curr. Biol. 2023; 33(7): 1358–1364.e4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilson LAB, Zajitschek SRK, Lagisz M, et al.: Sex differences in allometry for phenotypic traits in mice indicate that females are not scaled males. Nat. Commun. 2022; 13(1): 7502. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUsui T, Macleod MR, McCann SK, et al.: Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research. PLoS Biol. 2021; 19(5): e3001009. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBecker JB, Prendergast BJ, Liang JW: Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol. Sex Differ. 2016; 7(1): 34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeidari S, Babor TF, De Castro P, et al.: Sex and Gender Equity in Research: rationale for the SAGER guidelines and recommended use. Research Integrity and Peer Review. 2016; 1(1): 2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan Epps H, Astudillo O, Del Pozo Martin Y, et al.: The Sex and Gender Equity in Research (SAGER) guidelines: Implementation and checklist development. European Science Editing. 2022; 48: 48. Publisher Full Text\n\nKennedy BK, Berger SL, Brunet A, et al.: Geroscience: Linking Aging to Chronic Disease. Cell. 2014; 159(4): 709–713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJackson SJ, Andrews N, Ball D, et al.: Does age matter? The impact of rodent age on study outcomes. Lab. Anim. 2017; 51(2): 160–169. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrust V, Schindler PM, Lewejohann L: Lifetime development of behavioural phenotype in the house mouse (Mus musculus). Front. Zool. 2015; 12(1): S17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVos T, Lim SS, Abbafati C, et al.: Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396(10258): 1204–1222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBanzi R, Camaioni P, Tettamanti M, et al.: Older patients are still under-represented in clinical trials of Alzheimer’s disease. Alzheimers Res. Ther. 2016; 8(1): 32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Vries RBM , Hooijmans CR, Langendam MW, et al.: A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies. Evidence-based Preclinical Medicine. 2015; 2(1): 1–9. Publisher Full Text\n\nMoher D, Shamseer L, Clarke M, et al.: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015; 4(1): 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMunn Z, Stern C, Aromataris E, et al.: What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences. BMC Med. Res. Methodol. 2018; 18(1): 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCommission; E: Summary Report on the statistics on the use of animals for scientific purposes in the Member States of the European Union and Norway in 2019. Brussels: 2022.\n\nFinding a random set of citations in EndNote. http\n\nBahor Z, Liao J, Currie G, et al.: Development and uptake of an online systematic review platform: the early years of the CAMARADES Systematic Review Facility (SyRF). BMJ Open Science. 2021; 5(1): e100103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNielsen MW, Andersen JP, Schiebinger L, et al.: One and a half million medical papers reveal a link between author gender and attention to gender and sex analysis. Nat. Hum. Behav. 2017; 1(11): 791–796. PubMed Abstract | Publisher Full Text\n\nMacleod MR, O’Collins T, Howells DW, et al.: Pooling of Animal Experimental Data Reveals Influence of Study Design and Publication Bias. Stroke. 2004; 35(5): 1203–1208. PubMed Abstract | Publisher Full Text\n\nSeyhan AA: Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles. Translational Medicine Communications. 2019; 4(1): 18. Publisher Full Text\n\nBaker M: 1,500 scientists lift the lid on reproducibility. Nature. 2016; 533(7604): 452–454. PubMed Abstract | Publisher Full Text\n\nMunafò MR, Nosek BA, Bishop DVM, et al.: A manifesto for reproducible science. Nat. Hum. Behav. 2017; 1: 0021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDirnagl U, Bannach-Brown A, McCann S: External validity in translational biomedicine: understanding the conditions enabling the cause to have an effect. EMBO Mol. Med. 2022; 14(2): e14334. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee PY, Alexander KP, Hammill BG, et al.: Representation of Elderly Persons and Women in Published Randomized Trials of Acute Coronary Syndromes. JAMA. 2001; 286(6): 708–713. PubMed Abstract | Publisher Full Text\n\nDiederich K, Steinfath M, Bannach-Brown A, et al.: Systematic Review of Age and Sex in Preclinical Models of Age-Correlated Diseases. OSF. 2024.\n\nDiederich K, Steinfath M, Bannach-Brown A, et al.: Systematic Review of Age and Sex in Preclinical Models of Age-Correlated Diseases. GitHub; 2024."
}
|
[
{
"id": "327825",
"date": "16 Oct 2024",
"name": "Devin Wahl",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the current analysis, Diederich et al. suggest to perform a systematic review of animal studies to assess the age and sex of mice used in basic research on age-related human diseases. The authors choose to focus on five major diseases (the leading causes of death worldwide). The authors will use The Systematic Review Centre for Laboratory Animal Experimentation’s protocol template and the PRIMSA-P checklist. Importantly, the authors suggest to perform these analyses at several timepoints (2013 and 2023), thus providing insight into how these factors have changed within the last 10 years. The authors also will examine clinical trials via the assessment of Cochrane reviews (also examining the five diseases as described above).\nOverall, the manuscript is well written and easy to follow. In my mind I feel as if this these analyses will make a good contribution to the literature (and they are important). I have a couple of suggestions for the authors that might improve their analyses and contributions to this field.\nThe authors might provide more of a discussion on why they chose the five diseases. They provide a general overview; However, some readers might also appreciate, for example, a discussion of cancer because aging is also a leading cause of many types of cancers. This is just an example. The analyses would benefit (or at least a discussion would be appropriate) by also considering different mouse models. For example, one would assume that most of these mice are C57/B6. Would the authors suggest different genetic models or genetically diverse mice, and to what extent should those be included in the analysis? More of a discussion is necessary as that would strengthen the manuscript. How do the authors ‘compare’ the ages of mice and humans? In other words, how do the authors know that a six-months old mouse is comparable to a middle-aged human? It will be important o examine the literature on this.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "12835",
"date": "25 Nov 2024",
"name": "Kai Diederich",
"role": "Author Response",
"response": "Dear Dr. Devin Wahl, thank you for your positive review and critical analysis of our manuscript. We would like to clarify the specific issues raised in the following. Comment 1: The authors might provide more of a discussion on why they chose the five diseases. They provide a general overview; However, some readers might also appreciate, for example, a discussion of cancer because aging is also a leading cause of many types of cancers. This is just an example. Response: We thank the reviewer for this comment. We agree, that cancer is one of the major age-related diseases. Therefore, the question of selecting the most appropriate animal model for preclinical research also arises in this field. This will be discussed in detail in the manuscript of our meta-analysis. In order to include enough studies for each considered disease to ensure valid outcomes, we had to limit our review to a subset of diseases. These were selected according to the most recent assessment of the global burden of disease in 2019, published in 2020 (Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019, The Lancet, Volume 396, Issue 10258, 1204 – 1222). We chose to focus on the five leading causes of global disability-adjusted life years over the age of 75 in our systematic review, namely Alzheimer's disease, stroke, diabetes mellitus type 2, ischaemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD). Comment 2: The analyses would benefit (or at least a discussion would be appropriate) by also considering different mouse models. For example, one would assume that most of these mice are C57/B6. Would the authors suggest different genetic models or genetically diverse mice, and to what extent should those be included in the analysis? More of a discussion is necessary as that would strengthen the manuscript. Response: We thank the reviewer for this comment. We will include studies using mice (genus Mus) in vivo or ex vivo to investigate one of the five diseases under consideration. This encompasses both wild-type mice and genetically modified animals. This is a crucial consideration, for instance, when examining Alzheimer's disease models, as these predominantly comprise genetically modified animals. Additionally, the genetic model may influence the age of the animal. For instance, there are distinct transgenic animals for early-onset and late-onset Alzheimer's disease. Early-onset Alzheimer's is often associated with familial mutations in genes like APP (amyloid precursor protein), PSEN1(presenilin-1), and PSEN2 (presenilin-2), while late-onset Alzheimer's is linked more to complex genetic factors, such as the presence of the APOE ε4 allele and mutations in genes like TREM2, which affect microglial response. Therefore, in addition to sex and age, we investigate genetic modifications, as well as race, the supplier, the induction model for the specific disease and the presence of comorbidities. This is described in the section ‘Characteristics of the animal model and characteristics of the human patients’. These parameters will be discussed in detail in the manuscript of our meta-analysis. Comment 3: How do the authors ‘compare’ the ages of mice and humans? In other words, how do the authors know that a six-months old mouse is comparable to a middle-aged human? It will be important to examine the literature on this Response: Thank you for this very important comment. We have refrained from doing a direct numerical comparison. Since the duration of developmental phases in mice compared to humans are not uniformly correlated. It rather seems that especially the early life in mice is accelerated compared to humans (1). It is therefore not possible to simply take the absolute life span of humans and mice and to calculate a factor translating the age. However, some important biological processes can be defined in mice and humans and can provide a framework enabling drawing parallels in the age of both species. Thus, the mean duration of weaning period, puberty, adulthood, reproductive senescence and post senescence is known for mice and humans (1). Since we expect a strong discrepancy between the age of mice included in research studies and the age of human patients in clinical studies of age-correlated disease, we probably will not need an exact translation of the age but rather determine which part of a life stage the mice are in compared to humans. We have now included this discussion in the introduction of the manuscript and also added a new reference. 1. Dutta S, Sengupta P. Men and mice: Relating their ages. Life Sciences. 2016; https://doi.org/10.1016/j.lfs.2015.10.025"
}
]
}
] | 1
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https://f1000research.com/articles/13-858
|
https://f1000research.com/articles/13-1421/v1
|
25 Nov 24
|
{
"type": "Research Article",
"title": "Comparison of Scapulohumeral rhythm in individuals with and without Forward Shoulder Posture",
"authors": [
"Ganesh Balthillaya M",
"Shalini H",
"Indu Reddy",
"Kiransha R. Velingkar",
"Eliseus Chettiar",
"Divya S",
"Bhamini Krishna Rao",
"Shyamasunder Bhat N",
"Shalini H",
"Indu Reddy",
"Kiransha R. Velingkar",
"Eliseus Chettiar",
"Divya S",
"Bhamini Krishna Rao",
"Shyamasunder Bhat N"
],
"abstract": "Background Forward Shoulder Posture (FSP) is one of the most common postural deviations of the upper back, which may affect the scapulohumeral rhythm (SHR). This study aimed to investigate changes in scapulohumeral rhythm during scapular plane shoulder abduction between individuals with and without FSP.\n\nMethods A cross sectional study with two group comparison. Young adults with FSP (N=39) with a forward shoulder angle ≥ 52°and without FSP(N=40) with a forward shoulder angle < 52° were recruited for the study. Scapular upward rotation was measured with the help of two inclinometers during scapular plane shoulder abduction, at resting shoulder abduction, at 30°, 60°, 90°, 120°, 150°, and at full range of shoulder abduction, and SHR was calculated. The scapulohumeral rhythm was compared between the two groups using an independent t test.\n\nResults Data analysis showed a statistically significant difference in scapulohumeral rhythm at 30°(p=0.004), 60°(p=0.013), and 90°(p=0.009) shoulder abduction between the two groups. There were no significant differences in the other ranges of shoulder abduction between the two groups.\n\nConclusion Forward shoulder posture alters the scapulohumeral rhythm between 30 ° and 90°shoulder abduction. Clinicians, trainers, and sports therapists should be aware of this change to intervene at an early stage and prevent the development of pathological conditions around the shoulder.",
"keywords": [
"Round back posture",
"Scapulothoracic joint",
"Shoulder abduction"
],
"content": "Introduction\n\nThe scapular position and motion are considered the most important factors contributing to shoulder function. Abnormal scapulothoracic (ST) joint mechanics have been found to be associated with the development of pathological conditions of the shoulder, such as joint instability, impingement syndrome, rotator cuff tendinitis, and other overuse sports injuries of the shoulder.1,2 Overhead activities require coordinated and balanced movement of the humerus and scapula, scapulohumeral, and scapulothoracic articulations.3,4 Alterations in the coordination of movement between the scapulothoracic and scapulohumeral articulations affect the scapulohumeral rhythm.3–5\n\nForward Shoulder Posture (FSP) is one of the most common abnormal upper back postures. FSP is characterized by protraction of the acromion in front of the line of gravity (LOG), downward rotation, and anterior tilt of the scapula.6 Rounded shoulder posture (RSP) also deviates from the upper back, in which the shoulder is placed anterior to the plumb line in the coronal plane. Several methods have been proposed to measure the FSP.7–9 Thigpen et al. recommended measuring the forward shoulder angle (FSA) for the diagnosis of forward shoulder posture or round shoulder posture (RSP). FSA is the “angle between vertical line that cross C7 spinous process and the line that pass through the C7 spinous process and acromion”.9 The angle ≥52° was considered as FSP.9,10 Change in scapular position can cause muscle imbalance, alteration in scapulohumeral rhythm and finally may lead to impingement syndrome, shoulder pain and instability.1,10\n\nThe “scapulohumeral rhythm is the balanced and coordinated movement between the scapula and the humerus. The normal scapulohumeral rhythm and the contribution of scapular motion and humeral motion vary in different ranges of the shoulder complex.3 Coordinated and coupled movement of the scapula and humerus is very important to prevent movement impairments and pathological changes around the shoulder complex.11 Forward head posture and other postural deviations of the upper back and scapula are considered to contribute to changes in scapular motion and scapulohumeral rhythm.9 Alterations in scapular kinematics and scapulohumeral rhythm have also been reported in painful conditions of the shoulder.9 However, studies have not shown a clear relationship between the altered scapulohumeral rhythm and shoulder pain. The presence of pain during testing procedures is a major limitation in these studies, as it makes it difficult to determine the cause for alteration in scapulohumeral rhythm.9 We hypotheses that altered scapulohumeral rhythm would be present between individuals with and without FSP. The identification of altered scapulohumeral rhythm in FSP may provide a theoretical basis for the development of musculoskeletal conditions around the shoulder in FSP. The purpose of this study was to compare scapulohumeral rhythm in asymptomatic individuals with and without FSP and to determine whether there is any difference in scapulohumeral rhythm.\n\n\nMethods\n\nEthical considerations: Study protocol was approved by Ethics Committee of Kasturba Medical College and Kasturba Hospital Manipal (IEC 909-2018, dated 12/12/2018). Written informed consent was obtained by all the participants. All procedures were conducted in accordance with the 1964 Helsinki Declaration and its later amendments.\n\nParticipants: This was a cross-sectional study with two group comparisons. The study was conducted in department of physiotherapy, Kasturbha hospital manipal, during the period of 12th December 2018 to 12th March 2019. Seventy-nine young healthy individuals participated in the study through purposive sampling. Sample size was calculated using G-Power software, on the basis of effect size 0.75 (determined by a pilot study), an alpha value 0.05 and desired power of 90%. Individuals age group–20-40 years and with normal shoulder range of motion included in the study. Participants with a forward shoulder angle ≥ 52° on the dominant side were included in the Forward Shoulder Posture (FSP) group (N=39) and participants with a forward shoulder angle < 52° on the dominant side were included in the without Forward Shoulder Posture (FSP) group (N=40). Participants with a history of surgery or traumatic injuries in the upper quarter, pain in the upper quarter within six months of testing, and neuromuscular or musculoskeletal conditions affecting the upper quarter were excluded from the study. Hundred and twelve participants screened for study thirty-three participants excluded from the study as they did not meet the criteria.\n\nForward Shoulder Posture assessment: FSP was determined by measuring the forward shoulder angle (FSA) according to the technique suggested by Thigpen et al.9 FSA was measured in the screening phase by the photogrammetric method. A digital camera was placed four feet in height and seven feet away from the participant. Participants were asked to stand and look forward while maintaining a natural posture. To facilitate the natural posture, participants were asked to move their arms up and down above the head, move their head front and back, and take deep breath three times. The posterolateral part of the acromion process and C7 spinous process were palpated, markers were placed, and photographs were taken from the lateral view. The images were then transferred to a personal computer. The angle formed by the line passing through the C7 spinous process and acromion with a vertical line at the C7 spinous process was measured using an MB-ruler (free software to measure angle and distance) as the FSA. FSA was measured for the dominant and non-dominant sides, and participants with FSA ≥ 52° on the dominant side were considered the Forward Shoulder Posture (FSP) group. Initial screening, measurement of forward shoulder angle, and group allocation were performed by tester 1.\n\nScapulohumeral rhythm (SHR) assessment: The SHR was calculated by measuring scapular upward rotation according to the procedure recommended by Watson et al.12 Two inclinometers were used to measure scapulohumeral rhythm. One inclinometer was used to measure shoulder elevation, and the other was used to measure upward scapular rotation. Measurement of scapulohumeral rhythm was performed during shoulder abduction with elbow full extension, wrist in neutral position, and thumb leading in the scapular plane in relaxed barefoot standing. The first inclinometer was Velcro taped to the humerus just below the deltoid insertion. The dial of the inclinometer rotated such that the dial reading 0° corresponded to the vertical direction. The scapular upward rotation was measured using a second inclinometer by manually aligning the base of the inclinometer along the spine of the scapula during shoulder abduction. Participants were asked to move the shoulder actively from the resting position to 30°, from rest to 60°, from rest to 90°, from rest to 120°, from rest to 150°, and from rest to full range of shoulder abduction, and to hold each position for measurement. Shoulder abduction was measured by the first inclinometer by tester -2 and scapular upward rotation was recorded by 2nd Inclinometer by tester -3. Scapular Upward Rotation (SUR) was recorded at the shoulder at rest, at 30°, 60°, 90°, 120°, and 150°, and at full range of shoulder abduction. We conducted reliability testing of the procedure. The procedure was found to be reliable (ICC=0.91) for the measurement of scapular upward rotation at rest, at 30°, 60°, 90°, 120°, and 150°, and at full range of shoulder abduction. Tester-2 and tester-3 were blinded to the group allocation. SHR was calculated as GH elevation/SUR (GH elevation = total shoulder motion-SUR). SHR was measured for dominant upper extremity.\n\nData analysis: The Statistical analysis was conducted using SPSS software version 16.0. Demographic data were analyzed using descriptive statistics. The level of statistical significance was set at P < 0.05. The normality of the data was assessed using the Kolmogorov-Smirnov test. The data were normally distributed. An independent sample t test was used to compare scapulohumeral rhythm between the two groups.\n\n\nResults\n\nA total of 79 participants (39 in the FSP group and 40 in the non-FSP group) were included in the study. The demographic characteristics of the participants are shown in Table 1.\n\nUpward rotation of the scapula at resting shoulder abduction was compared between the FSP and without FSP groups. There was no significant difference in upward rotation of the scapula in the resting shoulder position between the two groups ( Table 1). The independent sample t test revealed a significant difference in SHR at 30°, 60°, and 90° of shoulder abduction between the FSP and without FSP group (Table 2). The difference in scapulohumeral rhythm was not significant at 120°, 150°, and full range of shoulder abduction.\n\n\nDiscussion\n\nThe purpose of this study was to compare SHR in people with and without FSP. SHR are a key factor in the development of shoulder impairments. Understanding the relationship between SHR and FSP by comparing SHR between individuals with and without FSP may provide valuable information for planning treatment protocols to prevent shoulder impairments. FSP and other postural deviations of the upper back are common in young adults owing to poor postural habits, including the use of smartphones, computers, or laptops. In the current study, young healthy asymptomatic individuals were selected as participants, as postural deviations of the upper back are common in this group. Participants were grouped into the FSP and without FSP groups according to the FSA on the dominant side. To reduce the influence of hand dominance on scapulohumeral rhythm, the SHR was compared on the dominant side in both groups. To the best of our knowledge, no previous study has compared scapulohumeral rhythm between FSP and without FSP. The results of this study revealed that the SHR was significantly greater at 30°, 60°, and 90° of shoulder abduction in the FSP group than in the non-FSP group. This finding indicates that scapular upward rotation is relatively less during shoulder abduction between 30° and 90° of shoulder abduction in persons with FSP than in those without FSP. In this study, we directly compared the scapulohumeral rhythm during shoulder abduction at different angles between the FSP and without FSP groups. Previous reports have compared scapular kinematics and scapular muscle activities to determine their relationship with head and shoulder posture.7,13,14\n\nStudy by Thigpen et al. compared the scapular kinematics and muscle activity in forward shoulder head posture and Ideal posture during loaded flexion task and reaching tasks.9 There was increased upward rotation of scapula in forward shoulder head posture group compared with ideal posture group during loaded flexion and reaching tasks.9 However, findings of current study cannot be compared with this study due to methodological differences. Scapular upward rotation was assessed during loaded flexion and reaching tasks and in current study scapular rotation was measured during free abduction of the arm in the scapular plane.\n\nAbnormal alignment or posture such as FSP are potential risk factors for the development of shoulder pathologies.7 Relationship between posture and impairment at the shoulder is theorized, but not supported by evidence.9 Sahrmann has proposed the link between alignment deviations and impairment, “alignment deviations are likely to be linked to movement dysfunction and movement dysfunction subsequently leads to impairment”.9 Finding of current study support the Sahrmans proposal by demonstrating connection between alignment and movement dysfunction. According to previous reports, scapular kinematics and scapular muscle activity are affected by head and shoulder posture during shoulder elevation and overhead activities in asymptomatic individuals.7,12,13 The current study also supported the hypothesis that FSP impacts scapular mechanics independent of shoulder pain.\n\nLimitations of the current study: 1) Scapulohumeral rhythm was measured only in the scapular plane, and 2) the influence of neck and thoracic posture on forward shoulder angle and scapulohumeral rhythm were not considered.\n\nFuture research should consider the categorization of participants based on neck posture, shoulder posture, and thoracic posture to reveal a better understanding of the pattern of alteration in scapulohumeral rhythm.\n\n\nConclusion\n\nStructural alterations such as the Forward Shoulder Posture (FSP) affect scapular kinematics, at least in some ranges of shoulder abduction, which may be a sign of pathomechanical alteration leading to impairment in later stages. We suggest that clinicians, trainers, and sports therapists should be aware of this change to intervene in the early stages and prevent the development of shoulder impairment.\n\n\nEthical review and patient consent\n\nEthical considerations: Study protocol was approved by Ethics Committee of Kasturba Medical College and Kasturba Hospital Manipal (IEC 909-2018, dated 12/12/2018). Written informed consent was obtained by all the participants. All procedures were conducted in accordance with the 1964 Helsinki Declaration and its later amendments.\n\n\nORCID IDs\n\nGanesh Balthillaya M: https://orcid.org/0000-0002-2249-0181\n\nBhamini Krishna Rao: https://orcid.org/0000-0002-2708-0245\n\nShyamasunder N. Bhat: https://orcid.org/0000-0001-9545-4838",
"appendix": "Data availability\n\nThe data used for the current manuscript will available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0) in Figshare: Comparison of scapulohumeral rhythm in individuals with and without forward shoulder posture, https://doi.org/10.6084/m9.figshare.27311667.v2.15\n\n\nAcknowledgement\n\nWe are grateful to the Manipal College of Health Professions (MCHP) and Manipal Academy of Higher Education (MAHE) Manipal for providing logistic support and infrastructure for conducting this study.\n\n\nReferences\n\nBorstad JD: Resting Position Variables at the Shoulder: Evidence to Support a Posture-Impairment Association. Phys. Ther. 2006; 86(4): 549–557. PubMed Abstract | Publisher Full Text\n\nScibek JS, Carcia CR: Assessment of scapulohumeral rhythm for scapular plane shoulder elevation using a modified digital inclinometer. World J. Orthop. 2012; 3(6): 87–94. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHossein S, Anbarian M, Asghar A, et al.: The comparison of scapular upward rotation and scapulohumeral rhythm between dominant and non-dominant shoulder in male overhead athletes and non-athletes. Man. Ther. 2015; 20(6): 758–762. PubMed Abstract | Publisher Full Text\n\nYoshizaki K, Hamada J, Tamai K, et al.: Analysis of the scapulohumeral rhythm and electromyography of the shoulder muscles during elevation and lowering: Comparison of dominant and nondominant shoulders. J. Shoulder Elb. Surg. 2009; 18: 756–763. PubMed Abstract | Publisher Full Text\n\nMcquade KJ, Gary I: Smidt. Dynamic Scapulohumeral Rhythm: The Effects of External Resistance during Elevation of the Arm in the Scapular Plane. J. Orthop. Sports Phys. Ther. 1998; 27(2): 125–133. PubMed Abstract | Publisher Full Text\n\nKim E, Kim JS: Correlation between rounded shoulder posture, neck disability indices, and degree of forward head posture. J. Phys. Ther. Sci. 2016; 28(10): 2929–2932. PubMed Abstract | Publisher Full Text | Free Full Text\n\nyoo W-g: Comparison of Shoulder Muscles Activation for Shoulder Abduction between Forward Shoulder Posture and Asymptomatic Persons. J. Phys. Ther. Sci. 2013; 25: 815–816. Publisher Full Text\n\nKluemper M, Uhl T, Hazelrigg H: Effect of Stretching and Strengthening Shoulder Muscles on Forward Shoulder Posture in Competitive Swimmers. J. Sport Rehabil. 2006; 15: 58–70. Publisher Full Text\n\nThigpen CA, Padua DA, Michener LA, et al.: Head and shoulder posture affect scapular mechanics and muscle activity in overhead tasks. J. Electromyogr. Kinesiol. 2010; 20(4): 701–709. PubMed Abstract | Publisher Full Text\n\nHajibashi A, Amiri A, Sarrafzadeh J, et al.: Effect of Kinesiotaping and Stretching Exercise on Forward Shoulder Angle in Females with Rounded Shoulder Posture. J. Rehabil. Sci. Res. 2014; 1: 78–83.\n\nKibler WB, Sciascia A, Wilkes T: Scapular Dyskinesis and Its Relation to Shoulder Injury. J. Am. Acad. Orthop. Surg. 2012; 20(8): 364–372. Publisher Full Text\n\nWatson L, Balster SM, Finch C, et al.: Measurement of scapula upward rotation: a reliable clinical procedure. Br. J. Sports Med. 2005; 39: 599–603. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKebaetse M, Mcclure P, Pratt NA: Thoracic Position Effect on Shoulder Range of Motion, Strength and Three-Dimensional Scapular Kinematics. Arch. Phys. Med. Rehabil. 1999; 80: 945–950. PubMed Abstract | Publisher Full Text\n\nLudewig PM, Reynolds JF: The Association of Scapular Kinematics and Glenohumeral Joint Pathologies. J. Orthop. Sports Phys. Ther. 2009; 39(2): 90–104. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBalthillaya GM: Comparison of Scapulohumeral rhythm in individuals with and without Forward Shoulder Posture. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "344532",
"date": "11 Dec 2024",
"name": "Peter Rundquist",
"expertise": [
"Reviewer Expertise Shoulder complex kinematics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction Your last sentence in the first paragraph is a bit strong. Adding may between articulations and affect would be appropriate.\nYou have an open quotation mark in the third paragraph without a closed quotation mark.\nHypotheses in the third paragraph should be hypothesize. Additionally, the term significant should be added to both your hypothesis and purpose.\nMethods Your method of determining FSP was slightly different than that proposed by Thigpen et al. What is your rationale for the difference? Additionally, how reproducible was the methods you used? The reproducibility question must be addressed to make the article scientifically sound.\nYour method for evaluating scapular upward rotation utilized different elevation angles than Watson et al used. What is your rationale for the difference?\n\nIt is unclear if data was collected in the frontal or scapular plane.\nResults To avoid a type 1 error across so many pairwise comparisons, your significance level should be less than or equal to 0.0083 (0.05/6). Based on this, your only significant difference was at 30 degrees. This must be addressed to make the article scientifically sound.\nDiscussion Did you collect enough data from left hand dominant participants to discuss differences at least narratively between them and right hand dominant participants?\nData Table You have too many significant digits in several of your SHR columns.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "344533",
"date": "31 Dec 2024",
"name": "Kalyana Chakravarthy Bairapareddy",
"expertise": [
"Reviewer Expertise Physiotherapy and Rehabilitation"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript explores an important topic, addressing the impact of forward shoulder posture on scapulohumeral rhythm. The study design, statistical analysis, and discussion provide valuable insights, but there are areas for improvement to enhance the clarity, rigor, and applicability of the findings.\nMajor Comments: 1. The introduction provides a good background on FSP and SHR, but the hypothesis could be more explicitly stated. Consider clearly defining what the expected differences in SHR between FSP and non-FSP groups are. 2. Sampling Method: While purposive sampling is mentioned, it would be helpful to clarify why this method was chosen and how potential biases were minimized. 3. The use of inclinometers is appropriate, but more detail on calibration and measurement reliability would strengthen the study’s validity. 4. Control of Confounders: The authors briefly mention controlling for hand dominance. However, the influence of other potential confounders (e.g., thoracic spine posture) could be addressed more thoroughly. 5. While appropriate statistical tests are used, the results section could benefit from more detailed reporting. Specifically, confidence intervals alongside p-values would provide more context about the precision of the estimates. Additionally, the statistical analysis in the manuscript primarily relies on independent t-tests to compare scapulohumeral rhythm (SHR) at various angles of shoulder abduction between Forward Shoulder Posture (FSP) and non-FSP groups. While this approach provides basic comparisons, the study can benefit from more advanced methods that account for the repeated measurements across different angles and improve the robustness of the analysis. 6. The discussion effectively relates findings to existing literature. However, the clinical implications should be expanded. For example, how should physical therapists adjust interventions based on these findings? 7. The authors acknowledge limitations but do not discuss how these limitations might influence the interpretation of their results.\nMinor Comments: 1. The tables provide clear data, but adding graphical representations (e.g., bar charts for SHR differences) could improve reader comprehension. 2. While citations are extensive and relevant, ensuring consistency in formatting (e.g., spacing, punctuation) would improve professionalism.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "353042",
"date": "07 Jan 2025",
"name": "Y. Ravi shankar Reddy",
"expertise": [
"Reviewer Expertise Physical therapy and Rehabilitation."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReviewers Report. Abstract\nSpecify the exact measurement methods for scapular upward rotation and shoulder abduction briefly in the methods section of the abstract. Include confidence intervals alongside p-values for the results to improve statistical clarity. Add one sentence about the clinical relevance of altered scapulohumeral rhythm in FSP to strengthen the conclusion. Clarify the rationale for focusing on the scapular plane in the study.\n\nIntroduction\nExplicitly state the hypothesis, including the expected differences in scapulohumeral rhythm between FSP and non-FSP groups. Discuss why the scapular plane was chosen for measuring scapulohumeral rhythm rather than other planes of motion. Elaborate on the significance of studying asymptomatic individuals with FSP to the clinical understanding of musculoskeletal conditions. Add a brief explanation of how altered scapulohumeral rhythm might lead to long-term pathological conditions. Correct the grammatical error in the last paragraph: \"hypotheses\" should be \"hypothesize.\"\n\nMethods\nJustify the choice of purposive sampling and explain measures taken to minimize selection bias. Provide details on how the inclinometers were calibrated and validated before use. Explain why Thigpen et al.'s method for determining FSP and Watson et al.'s method for scapular upward rotation were modified. Include information on whether data were collected in the frontal or scapular plane to avoid ambiguity. Address how confounding factors such as thoracic spine or neck posture were controlled or accounted for. State whether adjustments for multiple comparisons (e.g., Bonferroni correction) were considered to avoid Type I errors.\n\nDiscussion\nExpand on the clinical implications of the findings, such as how physical therapy protocols could be adjusted to address altered SHR in FSP. Discuss the impact of the study’s findings on early detection and intervention strategies for shoulder pathologies. Compare the study’s findings directly with Thigpen et al.’s and Watson et al.’s studies, emphasizing differences in methods and outcomes. Address how measuring scapulohumeral rhythm solely in the scapular plane might limit the generalizability of the results. Elaborate on how the limitations (e.g., no control of thoracic posture) might influence the study’s interpretation and application.\n\nConclusion\nSummarize specific takeaways for clinicians and sports trainers, such as the importance of monitoring scapulohumeral rhythm between 30° and 90° shoulder abduction. Recommend future research to investigate scapulohumeral rhythm in other planes of motion or with consideration of thoracic and neck posture.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1421
|
https://f1000research.com/articles/12-1/v1
|
03 Jan 23
|
{
"type": "Research Article",
"title": "Expression of modified enhanced green fluorescent polyarginine protein in Saccharomyces cerevisiae INVSc1",
"authors": [
"Shania Safera Tandio Saputro",
"Khayu Wahyunita",
"Astutiati Nurhasanah",
"Yudhi Nugraha",
"Irvan Faizal",
"Sabar Pambudi",
"Andri Pramesyanti Pramono",
"Shania Safera Tandio Saputro",
"Khayu Wahyunita",
"Astutiati Nurhasanah",
"Yudhi Nugraha",
"Irvan Faizal",
"Sabar Pambudi"
],
"abstract": "Background: The enhanced green fluorescent protein (EGFP) gene is a reporter gene that can be used to optimize protein isolation procedures and the functional working of a transduction protein. EGFP, with the addition of eleven arginine residues, has been engineered to functionally improve the protein transduction process, which can later be used for cell reprogramming like induced pluripotent stem cells. The addition of six histidine amino acid residues at its C-terminal is intended for the protein isolation process using the His-tag antibody. Methods: The study aimed to investigate the optimization of the EGFP polyarginine protein expression in Saccharomyces cerevisiae in sufficient quantities for the protein isolation stage. This study also analyzed EGFP expression without polyarginine to analyze the polyarginine addition effect on expression processes. Protein expression was qualitatively measured by looking at expression fluorescence and protein levels of EGFP and EGFP - PolyR proteins. Results: Bands on Western Blots with 6×His-tag monoclonal antibody (primary antibody) and Goat anti-mouse IgG HRP (secondary antibody) showed the EGFP polyarginine and EGFP proteins were expressed in Saccharomyces cerevisiae INVSc1 at relatively low levels. The lyticase incubation time modification and administration of 3-5 kDa microfilter to concentrate increased the yield of isolated protein. Conclusions: The sufficient amount of protein isolation in S. cerevisiae can be achieved by using lyticase and sonicators combination for the lysis process.",
"keywords": [
"Saccharomyces cerevisiae INVSc1 protein expression",
"EGFP protein",
"protein transductions."
],
"content": "Introduction\n\nEnhanced green fluorescent protein (EGFP) has often been used as a reporter for protein transport, especially in eukaryotic cells such as mammalian and yeast cells. EGFP was derived from green fluorescent protein (GFP), a commonly used reporter protein that does not require a substrate for it to fluoresce. The EGFP gene is a mutated version of the GFP gene, with P64L and S65T mutations. These mutations cause a higher emission intensity in EGFP relative to that of the wild-type GFP, and better thermal stability of the EGFP protein, especially in eukaryotic cells.1 EGFP can be used as a marker in optimizing protein isolation procedures and their functions. The fluorescence makes it easier for us to observe the localization of the expression of the protein. The intensity of EGFP fluorescence can also indicate the level of expression of the protein in a system. EGFP can also be used to study protein transfer, such as analysis of the work of a protein transduction system for cell reprogramming purposes.\n\nOne of the uses of cell reprogramming is manufacturing induced pluripotent stem cells. Induced pluripotent stem cells are expected to be used as therapeutic cells for patients. Cell reprogramming can be done using protein transduction, viral transduction, or chemicals. Cell reprogramming by viral transduction can activate oncogenic genes, whereas chemical methods are highly unspecific and cannot be interpreted clearly.2,3 On the other hand, protein transduction is reputed as a harmless method to deliver protein precisely. However, protein transduction has its disadvantages, such as low transduction efficiency in host cells. Therefore, research is needed to increase transduction proteins by modifying the target protein.\n\nPolyarginines are short polypeptides classified as non-amphipathic cell-penetrating peptides (NaCPP) and have cationic characteristics, including binding anionic lipid membranes; therefore, polyarginine can enter through the plasma membrane of eukaryotic cells. As a result, the NaCPP class is less toxic than the primary amphipathic and secondary cell-penetrating peptide (CPP). The NaCPP class uses endocytosis mechanisms with low concentrations for cellular uptake.4 The amount of added arginine amino acid residues affect the cellular uptake's efficiency level, whereas more arginine residues have a better efficiency level. Adding more than 15 amino acid residues decreases intracellular delivery efficiency.5 Proteins fused to polyarginine are more efficiently transduced into human iPS cells compared to those without the addition of CPP.6\n\nIn this research, we designed and constructed two proteins, EGFP and EGFP-PolyR. EGFP-PolyR is an EGFP protein with the addition of eleven arginine residues (polyarginine – polyR) at the C terminal of EGFP to be used as a transduction protein model for cell reprogramming purposes. The gene encoding EGFP and EGFP-PolyR was synthetically constructed and expressed in Saccharomyces cerevisiae INVSc1. The study aimed to investigate the pattern of EGFP-PolyR protein expression in S. cerevisiae INVSc1 compared to EGFP. This paper analyzes and discusses some of the possible improvements of EGFP and EGFP-PolyR protein expression in S. cerevisiae INVSc1.\n\n\nMethods\n\nThe gene encoding EGFP (GenBank Accession #U55762) and EGFP- PolyR (was synthetically made by IDT Custom Gene Synthesis cloned in a plasmid called pEGFP- PolyR, in such a way that it allowed sub-cloning of the gene with and without the polyR sequence, by using a different combination of restriction enzymes. In addition to the 11× arginine residues (polyR), codons encoding 6× histidine residues (6×His-tag) were also added downstream to the polyR codons. The synthetic gene was sub-cloned into pYES2CT, a Saccharomyces cerevisiae expression plasmid, during which the polyarginine codon either remained fused to the EGFP gene or was removed, creating recombinant pYES2CT pYES2CT-EGFP-PolyR or pYES2CT- EGFP, respectively. Since the pYES2CT plasmid has its own 6×His-tag downstream to its Multiple Cloning Sites (MCS), positioned in-frame with the EGFP and EGFP-PolyR codons, the expressed EGFP was expected to have one 6×His-tag, whereas the EGFP-PolyR were expected to have two.\n\nThe intended digested fragments sized 821 bp (EGFP-PolyR) and 733 bp (EGFP), were gel-purified using GenepHlow Gel/PCR kit (DFH004) (GeneAid, Taiwan) with 20 μL elution buffer. The DNA concentration was measured using a BioDrop-Duo UV/Vis spectrophotometer (Thomas Scientific, United States). Then, the DNA was stored at -20°C. Ligation was carried out following the T4 DNA ligase procedure as described by the manufacturer (Promega, United States). The ligation was performed at 4°C overnight, with a plasmid-insert volume ratio of 1:10.\n\nThe transformation into Escherichia coli TOP10 was carried out following the method of Abyadeh et al. (2017).7 Recombinant E. coli cells were cultured in LB with 100 μg/mL ampicillin. Transformation by heat shock was carried out using the Scilogex SCI-100HCM-Pro Digital Thermal Mixer (United States) at 42°C for 90 seconds. The selection of transformants was performed on LB agar with100 mg/mL ampicillin (LB Agar+Amp). Colony PCR was performed on selected transformants with pYES2CT-specific primers (Forward: 5’-AATATACCTCTATACTTTAACGTC-3'; Reverse 5’-GAGGGCGTGAATGTAAGCGTGAC-3') to verify the presence of intended inserts. PCR was done using Biometra Tone Thermal Cyclers (Analytik Jena AG, Germany) and carried out following the procedure from MyTaq Red Mix (Bioline, UK) manufacturer, for 35 cycles, with predenaturation (95°C) for 1 minute, denaturation for 15 seconds, annealing (55°C) for 15 seconds, elongation (72°C) for 10 seconds, and post elongation for 5 minutes.\n\npYES2CT-EGFP- PolyR and pYES2CT-EGFP plasmids were isolated using' WizardPlus SV minipreps DNA purification kit (A1330) (Promega, United States)' after being propagated in E. coli TOP10. Isolated plasmids were used to transform Saccharomyces cerevisiae INVSc1 with the lithium acetate (LiAc) method.8 Transformants were selected on minimal medium (MM) agar without uracil. Plasmids were isolated from transformant colonies using the MP Biomedicals yeast plasmid isolation kit (MP Biomedicals, United States, Cat. 112069400). PCR was carried out to confirm the success of the transformation using Biometra Tone Thermal Cyclers (Analytik Jena AG, Germany) and carried out following the procedure from MyTaq Red Mix (Bioline, UK) manufacturer, for 35 cycles, with an annealing temperature of 55°C. Colony PCR was performed on selected transformants with pYES2CT-specific primers (Forward: 5’-AATATACCTCTATACTTTAACGTC-3'; Reverse 5’-GAGGGCGTGAATGTAAGCGTGAC-3'), to verify the presence of intended inserts. PCR was done using Biometra Tone Thermal Cyclers (Analytik Jena AG, Germany) and carried out following the procedure from MyTaq Red Mix (Bioline, UK) manufacturer, for 35 cycles, with predenaturation (95°C) for 1 minute, denaturation for 15 seconds, annealing (55°C) for 15 seconds, elongation (720C) for 10 seconds, and post elongation for 5 minutes.\n\nS. cerevisiae's fast-growing diploid strain INVSc1 (Invitrogen Corporation) was used as a host cell for protein expression. The yeasts were cultured in yeast-extract peptone dextrose (YEPD) medium. Recombinant cells of S. cerevisiae INVSc1 were cultured in a minimal medium (MM) without uracil. Protein expression followed the user guide of the pYES2CT plasmid (Invitrogen, 2003), with several modifications. A single colony of recombinant S. cerevisiae INVSc1 carrying pYES2CT-EGFP or pYES2CT-EGFP- PolyR was inoculated into 3 mL of MM medium; the culture was then incubated at 30°C 230 rpm for 48 hours. After that, a 1-mL culture was taken to measure its OD600 value. Culture with OD600 = 0.4 were subcultured into 100 mL of induction medium (MM medium containing 2% galactose and 1% raffinose). After adding the induction medium, the cultures were further incubated for 48 to 72 hours. The culture was centrifuged at 5000 rpm for 10 minutes to harvest and stored in a freezer at -80 0C until further use.\n\nA 1 mL 10× diluted culture was centrifuged at 5000 rpm for five minutes. The pellet was then fixed with 500 μL 3.7% formaldehyde for 30 minutes. The cell suspension was centrifuged at 5000 rpm for 5 minutes, and the supernatant was discarded. as the remaining pellet was resuspended in 1 mL PBS 1×. A 50-μL fixed-cell suspension was placed in a well of 96-well plates (Thermo Scientific) to visualize the EGFP fluorescence under an inverted fluorescent microscope (Zeiss Axiovert 40 CFL, UK), (40× magnification, λex 488 nm and λem 507 nm). Fluorescent intensity was measured using ImageJ software, and delta intensity was calculated as follows:\n\nIntensityt is the fluorescent intensity at time t post-inoculation to induction medium\n\nIntensity0 is the fluorescent intensity at time 0 post-inoculation to induction medium\n\nLysis was carried out by sonication in combination with incubation in lyticase (Sigma-Aldrich). Pellet from 50 mL culture was prepared in 50 mL tubes, then 10 mL breaking buffer (1 mM EDTA, 5% glycerol, 1 mM PMSF, and 50 mM sodium phosphate, pH 7.4) was added, and the mixture was homogenized. Lysis was performed by sonication at 10 kHz for 10 minutes, alternating every 15 seconds between sonication and cooling on ice. When lyticase was used, sonication was performed after incubation in lyticase. After sonication, the mixture was centrifuged at 10,000 rpm for 10 minutes. Protein concentration was measured using the Pierce BCA Protein Assay kit (ThermoScientific, United States). The protein was concentrated by centrifugal microfiltration (Merck Amicon Pro Purification System, filter Molecular Weight Cut-Off (MWCO) 3 and 5 kDa).\n\nSodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was carried out following the modified Iqbal and Ahmad (2016) method. The protein sample was mixed with 6× SDS gel loading buffer (600 mM Tris-Cl pH 6.8, 12% SDS, 30% glycerol (v/v), 0.03% bromophenol blue, and 20 mM DTT) and run on 10 % SDS-PAGE gel at 100 V for 110 minutes until the bromophenol blue dye reached approximately 0.5 cm from the lower limit of the gel.9\n\nWestern blotting was also carried out following the method of Iqbal and Ahmad (2016), with several modifications. Protein was transferred from gel to membrane (transfer buffer: 300 mM glycine, 300 mM Tris, 0.05% SDS) using Pierce Power Blotter (Thermo Scientific, United States) set at 25 kV, 1.3 A for 25 minutes. Then, the membrane was washed six times with PBST (PBS, 1% Tween-20) before applying the primary antibody (Anti-6×His-Tag monoclonal antibody (Invitrogen, catalog number MA1-21315) in blocking buffer (5% skim milk (Merck, Germany) in PBST), with 1:3000 ratio). Then the membrane was incubated at 4°C overnight before applying the secondary antibody (Goat anti-mouse IgG HRP, Invitrogen, catalog number 31430 in blocking buffer, with a ratio of 1:20,000 ratio) for 60 minutes with shaking (70 rpm). Then, the substrate (SuperSignal West Femto Luminol, Thermo Scientific, United States) was used. The duration of the exposure was 20 minutes.\n\nTwo hundred microliter solution to be measured was placed in a well of the 96-well fluorescent plate. Measurement was performed using a fluorimeter set at λex 488 nm and λem 507 nm.\n\nAmino acid composition and physicochemical properties were analyzed using ProtParam,10 and hydrophilic amino acids were analyzed using ProtScale.10 The isoelectric point was measured using the protein Isoelectric Point Calculator.11 The tertiary structure was modeled via i-Tasser12 and AlphaFold,13,14 and the Protean3D was used for viewing to analyze whether the histidine and polyarginine were located in the outer regions.\n\n\nResults\n\nAfter digests and ligation processes were successfully performed (Figure 1 and Figure 2A), the ligation products, hereby called pYES2CT-EGFP and pYES2CT-EGFP-PolyR, for plasmid carrying egfp and egfp-polyR respectively, were propagated in E. coli TOP10. Plasmids isolated from this E.coli TOP10 that had been confirmed to have the correct size (Figure 2B) and carried the genes (Figure 2C) were then used to transform S. cerevisiae INVSc1. Screening of S. cerevisiae INVSc1 transformants was performed by PCR of purified plasmids. PCR results of positive colonies are presented in Figures 2D and 3.\n\nInsertion of EGFP-PolyR gene was performed using the enzymes BamH1 (position 519) and Not1 (position 577) (A), whereas EGFP gene was inserted into pYES2CT plasmid using BamHI and EcoRI, thus leaving the PolyR fragment out (B)\n\npEGFP-Poly R (lane 5) and pYES2CT (lane 7) were cut with restriction enzymes EcoRI and BamHI, where pEGFP-Poly R produced egfp gene (733 bp band), and pYES2CT produced vector (5905 bp band) (A). The 822 and 733 bp DNA were isolated from gel, and ligated to the 5932 and 5905 bp bands, respectively. Single digest (BamHI) of plasmids isolated from E.coli TOP10 transformed with pYES2CT-EGFP (lane 3 and 4) and pYES2CT-EGFP-Poly R (lane 5 and 6), in comparison to wild type pYES2CT (lane 2), showed that the plasmid sizes were correct (B). Also, colony PCR of E.coli confirmed the presence of the intended genes as 1037bp and 1098bp bands, representing the egfp and egfp-polyR, respectively (C). Transformed yeast colony screening was performed by PCR of plasmids purified from the yeast, using pYES2CT-specific primers. As a control, pYES2CT plasmid was used (lane K). Lanes 1-15 showed PCR amplification results of plasmids isolated from S. cerevisiae culture, transformed with pYES2CT (lanes 1-5), pYES2CT-EGFP-Poly R (lanes 6-10), and pYES2CT-EGFP (lanes 11-15). Amplification of pYES2CT without insert (lane 1-5) shows the same size amplicons as a positive control (K), which are 334 bp, amplification of pYES2CT-EGFP-Poly R produced amplicons of 1097 bp (lane 6-10), while the pYES2CT-EGFP produced amplicons of 1036 bp (lane 11-15) (D). Lane M is GeneRuler 1kb DNA Ladder (Thermo Scientific SM0312).\n\nTransformation positive controls are shown in A1 and B1, whereas the negative controls are in A2 and B2.\n\nThe growth curve showed that post-induction S. cerevisiae INVSc1 stayed longer at the exponential phase when not carrying any plasmid in comparison to the same strain with pYES2CT plasmids (Figure 4). The plasmid-carrying yeasts seemed to reach stationary phase 24 hours after inoculation to induction medium (Figure 4B and C), whereas the wild-type culture stayed at exponential phase for up to 64 hours (Figure 4A) before slowing down its growth. No significant growth of the recombinant yeasts was observed between 48-72 hours post-inoculation to the induction medium (Figure 4D).\n\nOptical densities were measured at λ=660nm, 48 hours, and 72 hours post-inoculation to induction medium of the wild-type and recombinant S. cerevisiae (D).\n\nThe fluorescence produced post-inoculation to induction medium by each recombinant yeast and wild-type yeast is presented in Figure 5A. The Δintensity was calculated and presented as a graph in Figure 5B. No significant fluorescence increase was seenwas observed between 48 – 72 hours in either the recombinant yeast carrying pYES2CT-EGFP or pYES2CT-EGFP-PolyR plasmid. There was no significant difference in intensity expressed by different constructs either.\n\nWestern blotting using anti-his-tag mouse monoclonal antibody (primary antibody) and Goat anti-mouse IgG HRP (secondary antibody) proved that the EGFP-PolyR and EGFP proteins were expressed in S. cerevisiae INVSc1 at similar but relatively low levels (Figure 6).\n\nThe Western blot was performed using an anti-his-tag antibody as the primary antibody.\n\nA combination of lyticase treatment and sonication, as well as using sonication only, was attempted to extract the expressed proteins. We also attempted variations of incubation length (two, three, and four hours) in lyticase combined with five minutes of sonication. The results showed that, although the addition of lyticase increased the protein yield, in comparison to using sonication only (as observable from Figures 6A laanes 8 and 10), prolonging the incubation time in lyticase had no effect on protein extraction (Figures 7A and 7B). Attempts to concentrate protein by microfiltration using a filter with MWCO 3 and 5 kDa did not show a significant difference (Figures 7C and 7D). Measurement of fluorescence using a fluorimeter showed that concentrating the protein using a 3 kDa filter managed to retain most of the protein in the retentate (Figure 7E).\n\nThe properties of the proteins were analyzed using ProtParam and Isoelectric Point Calculator, and the results are presented in Table 1.\n\nAA: amino acids; pI: Isoelectric point.\n\nModeling of the proteins was performed using iTasser, and the result is presented in Figure 8. The models show that in both proteins, EGFP and EGFP-PolyR, the 6xHis-tag is located outside the protein nucleus. Structural alignment using Protean3D software predicted that the presence of PolyR indeed affected the conformation of the fused protein, although not within the EGFP domain itself (Figure 7E and F).\n\nAlignment results of the proteins tertiary structures (E and F).\n\n\nDiscussion\n\nIn this study, PolyR was added to EGFP protein to function as a cell-penetrating peptide (CPP), which is commonly used as a carrier of protein into cells. Arginine-rich CPP has been used as a carrier for the intracellular delivery of various bioactive molecules such as proteins, peptides, and nucleic acids. The number of arginine residues used as CPP can affect the efficiency of cellular uptake and cytosolic release. It is well understood that high cellular uptake efficiency is achieved with 8-12 residues.15 Polyarginine as CPP also plays an essential role in forming hydrogen bonds with cell membrane protein groups.16\n\nExpression of EGFP protein, as inferred from the fluorescence and Western blot data, indicated that the induction of the recombinant cultures had been successful. Analysis performed at 48 and 72 hours post-inoculation to induction medium showed no increase in fluorescent intensity with time (Figure 5B). Thus, in the future, this could be used as a reference supporting that it would only take 48 hours of culturing for expression, hence being more time-efficient.\n\nIt is known that the addition of a CPP sequence can have a negative influence on recombinant protein yield.17 It was reported that ten arginines (R10) residues were added to the superfolder GFP (sfGFP) N-terminal in pBAD plasmid containing arabinose-inducible sfGFP gene with a C-terminal His tag. No recombinant R10-sfGFP was expressed by E. coli TOP10. However, the unmodified sfGFP gene expressed over 30 mg/L protein under the same condition.18 It was also reported that although the fluorescent protein obtained after purification showed a single band on SDS-PAGE, mass spectrometry (MS) analysis revealed truncation of the R10, leaving only two arginine residues present at the C-terminus upon expression when the position of R10 and His-tag was swapped relative to the sfGFP gene (i.e. His tag at the N-terminus and R10 at the C-terminus).19\n\nIn contrast to these previous findings, our result indicated that the addition of a PolyR group to the C-terminal of EGFP carrying C-terminal 6×His-tag did not seem to interfere with protein expression in S. cerevisiae INVSc1, as shown by the similar fluorescence (Figure 5B) and protein (Figure 6) levels expressed by yeasts carrying pYES2CT-EGFP band pYES2CT-EGFP-PolyR. In combination with the data from the proteins' tertiary structural predictions and alignment, this expression result indicated that the conformational change caused by the addition of PolyR did not affect the protein expression.\n\nWe must take into account, however, that the number of arginine residues in PolyR (11×R), the fluorescent gene, and the host used in our study differ from the aforementioned studies by Reddington18 and Patel.19 It would be interesting to observe whether relocating the 6×His-tag or the PolyR to different terminals would improve the protein expression as well as provide ease of purification since it is feared that the PolyR can interfere with the binding of 6×His-tag to Ni-NTA resin to be used for purification or the anti-His-tag antibody used for detection of expression.\n\nThe amount of protein expressed can also be influenced by codon preference. The EGFP and EGFP-PolyR encoding genes in this study used codon preference for expression in mammalian cells and had not been adapted for expression in yeast. Analysis of codon adaptation index (CAI) of EGFP-PolyR encoding gene using CAICal20 with S. cerevisiae codon usage table (CUT) from Codon Usage Database showed that the CAI value was 0.575 with GC content 62.3% and Nc 24.4, whereas the EGFP encoding gene had CAI value 0.593 with GC content 60.9% and Nc 27.8.\n\nAn alternative that could be attempted to improve the expression is codon optimization. Attempt to optimize the codons encoding the two proteins using ATGme, produced new sequences with better CAI value (0.805), GC content 40.6% and Nc 46.1 for EGFP, and CAI value 0.801, GC content 40.2% and Nc 48.1 for EGFP-PolyR. The optimized sequences are presented in Figure 9.\n\nRed indicates codons with frequency <10% in S. cerevisiae.\n\nNc is the effective number of codons used in a gene, which is calculated from codon usage data, independent of gene length and amino acid (aa) composition.21 Nc values might start from 20, where one codon is exclusively used for each aa, to 61, where all synonymous codons are used with equal frequency.21 CAI measures the deviation of a given protein coding gene sequence with respect to a reference set of genes. In this case, S. cerevisiae CUT was used as a reference. CAI value ranges from 0 to 1, being 1 if a gene always uses the most frequently used synonymous codons in the reference set.20 In terms of gene expression level, generally, a CAI of 1.0 is considered perfect, whereas a CAI of > 0.8 is regarded as good.\n\nDuring protein synthesis, genetic information encoded in messenger RNAs (mRNAs) is used to direct the synthesis of proteins. This process occurs with great accuracy and speed on the ribosome, using transfer RNAs (tRNAs) as adaptor molecules that carry the amino acids to the mRNA template. For this reason, many argue that designing a gene with CAI 1.0 and Nc 20 is not the best approach to get optimum expression since using only one type or low variations of the codon for each amino acid might overload certain types of tRNAs only, thus blocking or stalling the translation process, hence the protein expression. Therefore, it is sensible to compensate the CAI value to 0.8-1.0 by increasing the Nc value in order to spread the codon usage.\n\nThe lower growth curve of the transformant S. cerevisiae compared to the wild-type can be due to the growth inhibition factors of S. cerevisiae activated due to the addition of MM induction medium (2% galactose and 1% raffinose). Adding raffinose to the growth medium of S. cerevisiae can activate the programmed cell death formation of acetic acid. Guaragnella's study (2013) suggests that S. cerevisiae is resistant to programmed cell death via acetic acid because S. cerevisiae can compensate by activating retrograde mitochondria. Although programmed cell death is activated, they are not necessarily inhibited by growth.18 This can be seen in the growth curve of the modified protein transformant. The low growth curve of the transformant S. cerevisiae does not affect the expression of modified proteins (Figures 1 and 2). This is possible because plasmid vectors have been designed to express them in sufficient quantities within the cell.\n\nThe S. cerevisiae plasmid vector used in this study is a plasmid vector designed to express its proteins in the cell. This is intended so that the target protein produced is not mixed with other proteins produced as metabolites from S. cerevisiae. Yeast cell walls are relatively rigid structures due to the β(1,3)-glucans.19,20 Depending on the type of acid used for extraction, significantly higher degrees of polymerization have been reported.21 Furthermore, the degree of (1,3)-glucan polymerization may be affected by environmental conditions, as yeast uses two 1,3-glucan synthase complexes to varying degrees depending on the growth phase and carbon source.22 In their mature form, β1,3-glucan chains of stationary phase cells are moderately branched and contain about 3–4% β1,6-linked glucose residues.23 Stationary cell phase 1,3-glucan chains are moderately branched and contain about 3–4 percent 1,6-linked glucose residues in their mature form. The degree of branching of 1,3-glucan may also be affected by growth conditions.\n\nEfficient breakage of cell wall strength-providing components is necessary to remove intracellular compounds effectively.24 Incubation with lyticase in combination with sonication can increase protein yield. This is because lyticase can help break down the cell wall of S. cerevisiae, which is quite strong and rigid. The strength and flexibility structure of the cell wall of S. cerevisiae is composed predominantly of β(1,3)-glucans. The structure of β(1,3)-glucans are influenced by the environment and the nutrients it grows on. The possible addition of an MM induction medium may make the structure of β(1,3)-glucans stronger and difficult to lysis.\n\n\nConclusions\n\nThe expression results of protein EGFP and its PolyR fused counterpart, EGFP-PolyR indicated that the predicted conformational change caused by PolyR addition in EGFP-PolyR did not affect the expression levels, since both proteins were expressed at an equal level, albeit low. There is the possibility that this low expression level was caused by unoptimized codons used in the gene construct. The construct was not codon optimized for the expression host, S. cerevisiae INVSc1. Codon optimization might be attempted to improve the CAI and Nc values to better match the expression host.\n\nThe growth curve of the transformant S. cerevisiae decreased due to the addition of induction mediums, especially raffinose, although it did not affect the amount of expression of the target-modified protein. A sufficient amount of target modified proteins expression for protein isolation in S. cerevisiae by induction of galactose and raffinose can be achieved by using lyticase combined with sonicators in the process of lysis S. cerevisiae. The expression of the modified protein in S. cerevisiae is not affected by the addition of arginine.",
"appendix": "Data availability\n\nFigshare: Growth curve of Saccharomyces cerevisiae with and without plasmid insertion. A. Growth curve of Saccharomyces cerevisiae without plasmid, https://doi.org/10.6084/m9.figshare.19759018. 25\n\nFigshare: The fluorescence of Saccharomyces cerevisiae without transformation and with transformation (pYES2CT- EGFP/ EGFP plasmid, pYES2CT-EGFP- PolyR/EGFP Polyarginine plasmid) at OD 600 on 48 hours and 72 hours, https://doi.org/10.6084/m9.figshare.19762699. 26\n\nFigshare: Figure 1-5, https://doi.org/10.6084/m9.figshare.19767592. 27\n\nFigshare: Attachment, https://doi.org/10.6084/m9.figshare.19767589. 28\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe would like to thank Program SAME Direktorat Sumber Daya, Ditjen Diktiristek, Kemendikbud Tahun 2022, and LPPM UPNVJ for their support in this study.\n\n\nReferences\n\nMuhammad N, Kryuchkova N, Dworeck T, et al.: Enhanced EGFP Fluorescence Emission in Presence of PEG Aqueous Solutions and PIB1000-PEG6000-PIB1000 Copolymer Vesicles. Biomed. Res. Int. 2013 [cited 2022 Apr 26]; 2013: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBiswas D, Jiang P: Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells. Int. J. Mol. Sci. 2016 Feb 6 [cited 2022 Apr 26]; 17(2): 226. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nFukushima K, Liu S, Wu H, et al.: Supramolecular high-aspect ratio assemblies with strong antifungal activity. Nat. Commun. 2013 Dec 9 [cited 2022 Mar 4]; 4(1): 1–9.Reference Source\n\nMadani F, Gräslund A: Membrane Molecular Interactions and Induced Structures of CPPs. Methods Mol. Biol. 2022 [cited 2022 Apr 27]; 2383: 153–165. Publisher Full Text Reference Source\n\nSchmidt N, Mishra A, Lai GH, et al.: Arginine-rich cell-penetrating peptides. FEBS Lett. 2010 May [cited 2022 Mar 16]; 584(9): 1806–1813. Publisher Full Text Reference Source\n\nKaishima M, Ishii J, Matsuno T, et al.: Expression of varied GFPs in Saccharomyces cerevisiae: codon optimization yields stronger than expected expression and fluorescence intensity. Sci Reports. 2016 Oct 26 [cited 2022 Apr 26]; 6(1): 1–15.Reference Source\n\nAbyadeh M, Karimi Zarchi AA, Faramarzi MA, et al.: Evaluation of Factors Affecting Size and Size Distribution of Chitosan-Electrosprayed Nanoparticles. Avicenna J Med Biotechnol. 2017 [cited 2022 Apr 27]; 9(3): 126–132.PubMed Abstract | Free Full Text\n\nGietz RD, Schiestl RH: High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat. Protoc. 2007 Feb [cited 2022 Apr 27]; 2(1): 31–34. PubMed Abstract | Publisher Full Text\n\nIqbal J, Ahmad R: Analysis of Western Blot: A Protein Separating Technique.[cited 2022 Apr 26].Reference Source\n\nRemington SJ: Green fluorescent protein: A perspective. Protein Sci. 2011 Sep [cited 2022 May 9]; 20(9): 1509–1519. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHemdan ES, Zhao Y, Sulkowski E, et al.: Surface topography of histidine residues: a facile probe by immobilized metal ion affinity chromatography. Proc. Natl. Acad. Sci. U. S. A. 1989 [cited 2022 May 9]; 86(6): 1811–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBornhorst JA, Falke JJ: Purification of proteins using polyhistidine affinity tags. Methods Enzymol. 2000 [cited 2022 May 9]; 326: 245–254. Publisher Full Text Reference Source\n\nMohanty AK, Wiener MC: Membrane protein expression and production: effects of polyhistidine tag length and position. Protein Expr. Purif. 2004 [cited 2022 May 9]; 33(2): 311–325. PubMed Abstract | Publisher Full Text\n\nSchmitt J, Hess H, Stunnenberg HG: Affinity purification of histidine-tagged proteins. Mol. Biol. Rep. 1993 Oct [cited 2022 May 9]; 18(3): 223–230. Publisher Full Text Reference Source\n\nLyu SK, Kwon H: Preparation of cell-permeable Cre recombinase by expressed protein ligation. BMC Biotechnol. 2015 Feb 19 [cited 2022 Apr 26]; 15(1): 7–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNakase I, Noguchi K, Aoki A, et al.: Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active macropinocytosis induction and efficient intracellular delivery. Sci. Rep. 2017 Dec; 7(1): 1991. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAfzal-Javan F, Mobini-Dehkordi M: Amplification, Sequencing and Cloning of Iranian Native Bacillus subtilis Alpha-amylase Gene in Saccharomyces cerevisiae. Jundishapur J Microbiol. 2013 Oct 1 [cited 2022 Apr 26]; 6(8): 7371.Reference Source\n\nGuaragnella N, Ždralević M, Lattanzio P, et al.: Yeast growth in raffinose results in resistance to acetic-acid induced programmed cell death mostly due to the activation of the mitochondrial retrograde pathway. Biochim. Biophys. Acta, Mol. Cell Res. 2013 Dec 1; 1833(12): 2765–2774. PubMed Abstract | Publisher Full Text\n\nLiu D, Zeng XA, Sun DW, et al.: Disruption and protein release by ultrasonication of yeast cells. Innov. Food Sci. Emerg. Technol. 2013 Apr; 18: 132–137. Publisher Full Text\n\nMiddelberg APJ: Process-scale disruption of microorganisms. Biotechnol. Adv. 1995 [cited 2022 Apr 27]; 13(3): 491–551. PubMed Abstract | Publisher Full Text\n\nCingolani G, Petosa C, Weis K, et al.: Structure of importin-beta bound to the IBB domain of importin-alpha. Nature. 1999 May 20 [cited 2022 Jan 29]; 399(6733): 221–229. PubMed Abstract | Publisher Full Text\n\nCabib E, Drgonová J, Drgon T: Role of small G proteins in yeast cell polarization and wall biosynthesis. Annu. Rev. Biochem. 1998 [cited 2022 Apr 27]; 67: 307–333. PubMed Abstract | Publisher Full Text | Free Full Text\n\nManners DJ, Masson AJ, Patterson JC: The structure of a beta-(1 leads to 3)-D-glucan from yeast cell walls. Biochem. J. 1973 [cited 2022 Apr 27]; 135(1): 19–30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao J, Fleet GH: Degradation of DNA during the autolysis of Saccharomyces cerevisiae. J. Ind. Microbiol. Biotechnol. 2003 Mar 1 [cited 2022 Apr 27]; 30(3): 175–182. PubMed Abstract | Publisher Full Text Reference Source\n\nSaputro SST, Wahyunita K, Nurhasanah A, et al.:Growth Curve Optical Density of Sacharomyces cerevisiae wild-type, EGFP vector insertion and EGFP PolyR insertion.csv. figshare. Dataset.2022. Publisher Full Text\n\nSaputro SST, Wahyunita K, Nurhasanah A, et al.:The fluorescence of Saccharomyces cerevisiae without transformation and with transformation (pYES2CT- EGFP/ EGFP plasmid, pYES2CT-EGFP- PolyR/EGFP Polyarginine plasmid) at OD 600 on 48 hours. figshare. Dataset.2022. Publisher Full Text\n\nSaputro SST, Wahyunita K, Nurhasanah A, et al.: Figure 1-5. figshare. Figure.2022. Publisher Full Text\n\nSaputro SST, Wahyunita K, Nurhasanah A, et al.: Attachment. figshare. Figure.2022. Publisher Full Text"
}
|
[
{
"id": "159002",
"date": "03 Nov 2023",
"name": "Khomaini Hasan",
"expertise": [
"Reviewer Expertise Protein chemistry",
"protein engineering",
"enzymology",
"protein therapeutics",
"biocatalysis and biotransformation"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nPramono and Co-workers study on expression of recombinant Enhanced Green Fluorescent Protein (EGFP) with some modification with the addition of poly-R in order to help protein penetration within cells. In general, the work can be significantly improved, especially in terms of quality of the data due to lack of evidence that are correlated with the conclusions.\n\nFirst, as we read in the article, Pramono and co-workers were struggling on how to express and obtained the recombinant protein in sufficient amount. Even though, the Western Blot microscopic data which were presented in the manuscript confirms the success of protein expression, but the quality of SDS PAGE gels did not fully support their conclusion. The gel itself lacks some data and low quality, for instance, no clear molecular weight marker and the bands, which were considered as expressed proteins, were almost invisible.\n\nSecond, the quantitative methodology, which were conducted and presented here, is mostly not effective to be done, because most of them show unexpected results. For instance, when they claimed that the expressed protein was low, they did ultrafiltration with 5 kDa cutoff and resulted no significant improvement. They also failed to prove that additional 6-his-tag in the recombinant protein is useful for their experiment as well. In order to answer our curiosity on the 6-histag, I would suggest to do a protein purification, so the claim of structure model that were presented in the manuscript can be proven and relevant.\nThird, the claim on the effect of plasmid toward growth of the yeast is weak due to lack of repetition to the experiment. If the experiment is conducted triplicates, the potential bias can be reduced and the issue of reproducibility may not occur. Additionally, the genetic optimization which was conducted computationally are useless due to having no experimental data that support the claim.\n\nFourth, the quality of the figures is very poor in quality. The authors can improve by using a camera or similar equipment that meets the requirement of the quality.\nLastly, some mistypes can be prevented.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "177225",
"date": "06 Nov 2023",
"name": "Hisao Moriya",
"expertise": [
"Reviewer Expertise Yeast",
"overexpression",
"plasmid construction",
"systems biology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper, the authors attempted to express EGFP-polyR in S. cerevisiae. They concluded that EGFP was successfully expressed and that the addition of polyR had no effect on the expression level of EGFP.\nHowever, the expression level of EGFP in S. cerevisiae seems to be much lower than the high expression level we know, and there are many possible improvements. Since many papers have been published on heterologous expression of fluorescent proteins in yeast, the authors should objectively judge how their level of technology compares with them. For example, our gTOW vector system can \"express EGFP to the limit,\" and in that case it can express enough EGFP to be recognized by SDS-PAGE in total protein without Western blotting1,2.\nCodon optimization is also mentioned by the authors. On the other hand, most yeast researchers, including us, use yEGFP3, a codon-optimized EGFP that maximizes expression in yeast3, which the authors should try first.\nIn addition, for plasmid construction, you may want to consider introducing a strong homologous recombination cloning method, which is available in yeast4. Cell disruption by glass beads is also easier and less expensive than spheroplasting in yeast. In our experience, EGFP-his6 can be purified in large quantities with virtually no degradation. In fact, we have been using the above plasmid to express and purify yEGFP-his6 by glass bead disruption as a practical training for students. If necessary, the plasmid can be distributed by us.\nFinally, polyR is known to stall translation5, a finding that may be helpful when trying to express EGFP-polyR after successful mass expression of EGFP.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-1
|
https://f1000research.com/articles/13-1420/v1
|
25 Nov 24
|
{
"type": "Research Article",
"title": "Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study",
"authors": [
"Malavika Kulkarni",
"Hitesh Hasmukhlal Shah",
"Sanjana subbiah",
"Sushma Thimmaiah Kanakalakshmi",
"Laxmi Shenoy",
"RamaRani KrishnaBhat",
"Priya Genevieve D'mello",
"Malavika Kulkarni",
"Hitesh Hasmukhlal Shah",
"Sanjana subbiah",
"Laxmi Shenoy",
"RamaRani KrishnaBhat",
"Priya Genevieve D'mello"
],
"abstract": "Background “Osteogenesis imperfecta (OI)” is a heterogeneous group of inherited disorders involving collagen type I with a 10–30% incidence of bleeding diathesis placing these individuals at an increased risk of bleeding. Our study aims to ascertain the risk factors that increase the propensity of perioperative blood transfusions in pediatric population.\n\nMethods A single center retrospective observational study of patients aged <18 years undergoing orthopedic surgeries at our tertiary care hospital from January 2016 to August 2024 were included and each surgery was analyzed as a discrete event. Age, type of OI, number of osteotomies, and number of bones operated simultaneously were recorded. The fall in hemoglobin, requirement for blood transfusions and associated factors were analyzed.\n\nResults Amongst 53 individuals who underwent surgery, 141 procedures were analyzed. The mean age was 11.07± 5.29 years, majority (n=33;62.2%) were phenotypically type III OI, and 42/53 (79%) patients underwent multiple osteotomies. Significant hemoglobin fall was observed after surgery (p<0.001) and was considerable in patients undergoing various osteotomies (p=0.002). Older children showed a smaller drop in hemoglobin level. Patients with type III OI showed significant hemoglobin fall (1.82 ± 0.86 g/dL). The transfusion requirement was seen in 23 (16.3%) surgeries besides it was significant in those undergoing multiple osteotomies (p= <0.05).\n\nConclusion Our study inferred that the fall in hemoglobin was significant postoperatively in OI patients and was associated with younger age, type III OI, and multiple osteotomies. Before performing orthopedic surgeries on patients with OI, surgeons might consider the latter risk factors to explore therapeutic options aimed at reducing hemorrhage and improving outcomes.",
"keywords": [
"Bleeding diathesis",
"Osteogenesis imperfecta",
"Osteotomies",
"Perioperative bleeding"
],
"content": "Introduction\n\n“Osteogenesis imperfecta (OI)” also known as “brittle bone disease” is a rare congenital disease resulting from a defect in the type I collagen synthesis or processing with an incidence of 1:20000. It has a wide spectrum of presentations ranging from almost asymptomatic to severe forms causing increased bone fragility, skeletal deformity, and a range of extra-skeletal manifestations.1 Majority of the OI patients have pathogenic mutations in “COL1A1 or COL1A2” genes which code for alpha 1 and 2 chains of type I collagen which are abundant in bones, ligaments, and tendons. Collagen type 1 is produced less frequently and/or abnormally in dominant pathogenic variations. It is commonly known that the variation type, precise location, and implicated gene all affect the phenotypic presentation of these patients.2\n\nNumerous mutations linked to OI have been found; however, missense mutations mostly cause structural changes in the collagen protein, which results in a more severe phenotype, whereas stop mutations typically result in decreased collagen quantity and a mild phenotype.3 OI is well known for its clinical manifestations, which include blue sclera, hearing loss, ligament laxity, increased joint mobility, small stature, easy bruising, and normal enamel with dentin abnormalities. Bony manifestations include bone abnormalities, fractures from minor trauma, and the requirement for repeated orthopedic treatments.3\n\nOI is also associated with easy bruising and bleeding, often attributed to the increased fragility of capillaries and perivascular connective tissue that cannot constrict adequately. The clotting abnormalities in OI patients can be explained due to reduced collagen-induced platelet aggregation response surrounding the exposed sub endothelium, reduced platelet retention, and reduced levels of factor VIII.4,5 Previous research has also shown enlarged platelets, diminished retention of platelets, and decreased factor VIII (FVIII) as the possible reasons for the bleeding manifestation.6,7\n\nHowever, in OI patients even with normal coagulation profile, bleeding might still happen, which makes intraoperative bleeding unpredictable.8,9 The literature review revealed no studies involving the pediatric population in India and a few Western studies analyzing the perioperative blood loss in pediatric OI patients undergoing orthopedic surgeries. In a retrospective analysis of 23 OI patients, aged between 6 and 13 years, who underwent osteosynthesis for femoral shaft fractures or correction of femoral deformities, Persiani et al.10 from Italy identified predictive risk factors regarding intraoperative bleeding, revealing that patients affected by type III OI have a high risk of severe blood loss during surgery. Similarly, a study conducted in the United States by Pichard et al.11 examined a retrospective review of 22 pediatric OI patients who had 42 surgeries involving the insertion of 52 femoral rods. The results indicated that an increase in osteotomies was associated with an increase in adjusted mean blood loss (P = 0.05). Therefore, having access to autologous blood donations or a sufficient supply of blood products will help address the potential issue of increased perioperative blood loss, a crucial component of treatment, while organizing the care of patients with OI. Therefore, the purpose of this study is to determine the variables influencing perioperative blood loss and need for blood transfusion in pediatric OI patients undergoing osteotomies.\n\n\nMethods\n\nThis was a retrospective case-record-based study conducted in pediatric OI patients who underwent osteotomies at a tertiary care hospital. The research conducted in this study adhered to the principles outlined in the Declaration of Helsinki and was approved by the Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (IEC 363/2024) on 18th September 2024. A waiver of consent was granted as per our institutional ethics committee due to the retrospective nature of the study. Individual patient anesthesia records, daily progress notes, initial history, physical examination, and doctor instructions from each hospital stay were obtained through electronic records and analyzed. Variables in terms of age, type of OI, single or multiple osteotomies were collected. Additionally, hematologic parameters such as transfusion history, hemoglobin before and after surgery, and hemoglobin at discharge when available were collected. The factors associated with fall in hemoglobin postoperatively and requirement of blood transfusions were analyzed.\n\nDiscrete variables are represented as frequencies and percentages. Continuous data are shown as mean±SD. A chi-squared test was performed to assess the association between the parameters. Statistical significance was set at p <0.05. The data were analyzed using SPSS version 29.\n\n\nResults\n\nDuring our study period, 53 patients who underwent a total of 141 procedures during their stay in hospital were analyzed and each surgery was analyzed as a discrete event. Their mean age was 11.07±5.29 years; 4/53 (7.8%) were phenotypically type I OI, the majority (n=33; 62.2%) were phenotypically type III OI and the remaining 16/53 (30%) were type IV OI. 61/141 (43.3%) surgeries involved a single bone, and 80/141 (56.7%) surgeries involved multiple bones. Of 53 patients requiring osteotomies, 11/53 underwent once, 9/53 underwent twice, 17/53 (majority) underwent thrice, 7/53 underwent four times, 4/53 underwent five times, 3/53 underwent six times and only 2/53 underwent osteotomies seven times ( Table 1).\n\n\n\nA. Drop in hemoglobin\n\n1. During this study, it was noted that the fall in hemoglobin was statistically significant with multiple osteotomies (p=0.002) when compared to single osteotomy (p=0.297), and the total fall in hemoglobin between the pre-operative (12.22±1.06 g/dL) and post-operative (10.57±1.48 g/dL) period was also statistically significant (p≤0.001) ( Table 2).\n\n2. During our study, we noted that the hemoglobin drop significantly correlated with the age of the patients. Statistical analysis with a scatterplot diagram confirmed that as the age of our study population advanced the fall in hemoglobin reduced ( Figure 1).\n\n3. In this study, type III OI was associated with significant hemoglobin drop (p=0.01) ( Table 3) and post-hoc pairwise analysis (Kruskal Wallis testing) also confirmed that the hemoglobin fall was significantly associated with type III OI (p=0.008) when compared to other types of OI ( Table 4).\n\nB. Requirement of blood transfusion\n\n1. In this study, no blood transfusion was required in 58 single osteotomy and 60 multiple osteotomies (n=118; 83.7%). However, 3 single osteotomies and 20 multiple osteotomies required blood transfusions (n=23; 16.3%) which was statistically significant (p=0.001) ( Table 5; Figure 2).\n\n2. There was no significant correlation noted between age of the patient and the need for blood transfusions.\n\n3. In this study, we also analyzed the type of OI and requirement of transfusion, which showed that in 9 type I OI undergoing surgeries none required transfusion; in type III OI, 73 surgeries did not require transfusion and 15 surgeries required transfusion; in type IV OI, 36 surgeries did not require transfusion and 8 surgeries required transfusion, however none were significant (p=0.387) ( Table 5).\n\n* Significant p-value.\n\n* Significant p-value.\n\n* Significant p-value.\n\n* Significant p-value.\n\n\nDiscussion\n\n“Osteogenesis imperfecta” is a broad category of hereditary collagen type I diseases. Bony deformities, heart valvular lesions, cognitive abnormalities, and metabolic disturbances are frequently linked to OI. In addition to defective collagen synthesis, patients with OI have increased capillary fragility, decreased platelet retention, decreased levels of factor VIII, and deficient collagen-induced platelet aggregation that causes excessive bruising and widespread oozing from wound sites, thus surgical procedures performed on these patients are more likely to result in bleeding complications despite normal coagulation parameters which makes assessment of perioperative blood loss unpredictable and is of a major concern to the surgeons.2,3,5\n\nIn this study, 53 patients who underwent a total of 141 surgeries were analyzed (an average of 3 surgeries per patient) during their stay in hospital and each surgery was analyzed as a separate event. Their mean age was 11.07±5.29 years, the majority (n=33; 62.2%) were phenotypically type III OI, and 80/141 (56.7%) surgeries involved multiple bones. This is similar to the study by Ruck et al.,12 who conducted a retrospective analysis of 60 OI children undergoing femoral rodding, showed a mean age of 4 years which is lower when compared to our study, however, the majority (n=30/60) had type III OI which is similar to our study. The study by Persiani et al.10 was conducted on 23 patients aged between 6 and 13 years (mean - 8.9±1.9 years) affected by type III OI, wherein 42 osteotomies were done, and the majority (n=11/23) underwent an average of 3 osteotomies which is similar to our study.\n\nOur study showed a greater fall in hemoglobin in patients with multiple osteotomies done simultaneously (p=0.002) when compared to a single osteotomy and also the total fall in hemoglobin post-operatively was statistically significant (p≤0.001) which is similar to the study done by Persiani et al.10 that showed average effective blood loss increased significantly as the number of osteotomies increased (p=0.046). Thus, the use of a structured bleeding survey is more advantageous than laboratory measurements as there is little correlation between the severity of bleeding with the levels of a particular factor, and the standard tests do not accurately reflect in vivo hemostasis due to the unmeasurable contribution of numerous factors (such as vessel fragility or fibrinolysis).13–15\n\nThis study revealed a negative correlation between the age of the patients and a fall in hemoglobin, suggesting that older children had better tolerance for blood loss when compared to a younger age group. Similar findings were reported in the study by Pichard et al.,11 which involved a retrospective review of 22 patients. The oldest patient, who underwent surgery, was 21 years and 2 months old, and the youngest, who underwent surgery, was 1 year and 7 months old. Of the 42 surgeries examined, the mean blood loss was 197 cc, with older patients generally having lower adjusted mean blood loss, though this difference was not statistically significant (p=0.07). The most likely explanation offered is that while a larger bone’s radius of diameter and, hence, its area of bleeding may cause more bleeding, a larger patient with a larger total blood volume may be able to withstand more bleeding.11\n\nIn this study, type III OI showed a significant hemoglobin drop (1.82±0.86 g/dL; p=0.01) and post hoc analysis also confirmed that the hemoglobin fall was significantly associated with type III OI (p=0.008) when compared to the other types of OI which are similar to the study by Persiani et al.10 wherein patients affected by type III OI had a high risk of severe blood loss during surgery. The probable explanation is that type III OI is characterized by increased capillary fragility and an altered platelet function caused by platelet dysfunction due to alteration in collagen when compared to other types of OI.\n\nThe perioperative transfusion requirement in surgeries for OI patients was found to be 23/141 surgeries (16.3%) in this study. Our study is similar to the study by Pichard et al.11 wherein six blood transfusions were given with a transfusion rate of 14%. The study under reference revealed that the average blood loss among transfused patients was 279 cc. Additionally, patients who underwent transfusion had an adjusted blood loss of 0.330 as opposed to those who did not get blood transfusion, who had an adjusted blood loss of only 0.003. Our findings are in line with studies by Gooijer et al.16 and Oakley et al.,17 which found that 17% of OI patients needed blood transfusions following surgery. For this reason, it is crucial to be aware of the bleeding risk. Despite a normal pre-operative hematological assessment, several studies18–21 describe severe bleeding in OI patients as a result of surgery, thus in patients with OI, “American Society of Anesthesiologists transfusion guidelines” state, “platelet transfusion may be indicated despite an adequate platelet count if there are known platelet dysfunction and microvascular bleeding.” “Bleeding time and platelet aggregation tests are not useful in the operating room”, and “there is an urgent need for the development of clinically relevant measures of in vivo platelet function and bleeding risk to guide the rational use of platelet transfusion”.\n\nOur study showed incidence of transfusion was higher in those who underwent multiple osteotomies simultaneously (p=0.001) which is similar to the study by Persiani et al.10 wherein the perioperative transfusion requirement was more in type III OI but not statistically significant (p=0.387). These results were comparable to those of research by Hathaway et al.22 and others,23,24 which discovered aberrant platelet adhesion, poor platelet factor 3 (PF3) release, aberrant platelet aggregation to ADP, and commonly faulty platelet aggregation in type III OI patients, thus corroborating with our finding of increased transfusion requirement in type III OI patients. Since the relationship between genotype and phenotype is frequently less strict than previously believed due to variability in penetrance and expressivity, coinheritance of hemostatic defects, or superimposed genetic modifiers, a genomic search for the molecular basis of inherited clotting and platelet defects may not be as beneficial.15 When regular hemostasis testing revealed no repeatable anomaly in a group of individuals with a significant history of bleeding, Obaji et al.25 administered tranexamic acid or desmopressin, and they observed no bleeding in 90% of the patients at high risk of bleeding receiving an intervention which can be used in OI patients as well before surgery to reduce the bleeding incidence post operatively.\n\n\n\n1. Single-center study.\n\n2. Surgical time and duration of hospitalization were not recorded.\n\n3. Average blood loss during surgery was not quantified.\n\n\nConclusion\n\nThe most reliable indicators of perioperative bleeding and the need for transfusion in procedures involving OI patients were the patient’s age, the type of OI, and the number of osteotomies. Surgeons evaluating bleeding tendency in OI patients need to take these particular parameters into account to potentially prevent hemorrhagic consequences and improve overall outcomes.\n\nThe research followed the tenets of the Declaration of Helsinki. The institutional ethical committee namely Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (IEC 542/2019) approved all study protocols (IEC 363-2024) on 18th September 2024. A waiver of consent was granted as per our institutional ethics committee due to the retrospective nature of the study.",
"appendix": "Data availability\n\nFigshare: This study contains the underlying data for ‘Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study”. (https://figshare.com/s/5feb7e72a5648bf4263b)\n\nDOI: ( https://doi.org/10.6084/m9.figshare.27292956.v4)26\n\n• Data OI. xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Extended data for ‘Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study’. (https://figshare.com/s/5feb7e72a5648bf4263b)\n\nThis project contains the following extended data:\n\n• Strobe checklist\n\n• Proforma\n\n• Protocol\n\nDOI: (https://doi.org/10.6084/m9.figshare.27292956.v4)26\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nNil\n\n\nReferences\n\nMarini JC: Osteogenesis imperfecta--managing brittle bones. N. Engl. J. Med. 1998 Oct 1; 339(14): 986–987. Publisher Full Text\n\nEtich J, Leßmeier L, Rehberg M, et al.: Osteogenesis imperfecta-pathophysiology and therapeutic options. Mol. Cell Pediatr. 2020 Aug 14; 7(1): 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSubramanian S, Anastasopoulou C, Viswanathan VK: Osteogenesis Imperfecta. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 3]. Reference Source\n\nEvensen SA, Myhre L, Stormorken H: Haemostatic studies in osteogenesis imperfecta. Scand. J. Haematol. 1984 Aug; 33(2): 177–179. PubMed Abstract | Publisher Full Text\n\nMalfait F, De Paepe A: Bleeding in the heritable connective tissue disorders: mechanisms, diagnosis and treatment. Blood Rev. 2009 Sep; 23(5): 191–197. PubMed Abstract | Publisher Full Text\n\nPhonela SM, Goller R, Karsas M: Osteogenesis imperfecta: an overview. SA Orthop. J. 2020 Dec; 19(4): 229–234. Publisher Full Text\n\nRoss KE, Gibian JT, Crockett CJ, et al.: Perioperative Considerations in Osteogenesis Imperfecta: A 20-Year Experience with the Use of Blood Pressure Cuffs, Arterial Lines, and Tourniquets. Children (Basel). 2020 Nov 6; 7(11): 214. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWong RS, Follis FM, Shively BK, et al.: Osteogenesis imperfecta and cardiovascular diseases. Ann. Thorac. Surg. 1995 Nov; 60(5): 1439–1443. Publisher Full Text\n\nKeegan MT, Whatcott BD, Harrison BA: Osteogenesis imperfecta, perioperative bleeding, and desmopressin. Anesthesiology. 2002 Oct; 97(4): 1011–1013. PubMed Abstract | Publisher Full Text\n\nPersiani P, Ranaldi FM, Martini L, et al.: Treatment of tibial deformities with the Fassier-Duval telescopic nail and minimally invasive percutaneous osteotomies in patients with osteogenesis imperfecta type III. J. Pediatr. Orthop. B. 2019 Mar; 28(2): 179–185. PubMed Abstract | Publisher Full Text\n\nPichard CP, Robinson RE, Skolasky RL, et al.: Surgical blood loss during femoral rodding in children with osteogenesis imperfecta. J. Child. Orthop. 2009 Aug; 3(4): 301–305. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRuck J, Dahan-Oliel N, Montpetit K, et al.: Fassier-Duval femoral rodding in children with osteogenesis imperfecta receiving bisphosphonates: functional outcomes at one year. J. Child. Orthop. 2011 Jun; 5(3): 217–224. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGooijer K, Rondeel JMM, van Dijk FS , et al.: Bleeding and bruising in Osteogenesis Imperfecta: International Society on Thrombosis and Haemostasis bleeding assessment tool and haemostasis laboratory assessment in 22 individuals. Br. J. Haematol. 2019 Nov; 187(4): 509–517. PubMed Abstract | Publisher Full Text\n\nEvensen SA, Myhre L, Stormorken H: Haemostatic studies in osteogenesis imperfecta. Scand. J. Haematol. 1984 Aug; 33(2): 177–179. PubMed Abstract | Publisher Full Text\n\nFaqeih E, Roughley P, Glorieux FH, et al.: Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2. Am. J. Med. Genet. A. 2009 Mar; 149A(3): 461–465. PubMed Abstract | Publisher Full Text\n\nGooijer K, Heidsieck G, Harsevoort A, et al.: Bleeding assessment in a large cohort of patients with Osteogenesis Imperfecta. Orphanet J. Rare Dis. 2024 Feb 12; 19(1): 61. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOakley I, Reece LP: Anesthetic implications for the patient with osteogenesis imperfecta. AANA J. 2010 Feb; 78(1): 47–53. PubMed Abstract\n\nLangness U, Behnke H: Klinik und genetik der Osteogenesis imperfecta [Clinical picture and genetics of osteogenesis imperfecta]. Dtsch. Med. Wochenschr. 1970 Jan 30; 95(5): 209–212. passim. German. PubMed Abstract | Publisher Full Text\n\nWong RS, Follis FM, Shively BK, et al.: Osteogenesis imperfecta and cardiovascular diseases. Ann. Thorac. Surg. 1995 Nov; 60(5): 1439–1443. Publisher Full Text\n\nRothschild L, Goeller JK, Voronov P, et al.: Anesthesia in children with osteogenesis imperfecta: Retrospective chart review of 83 patients and 205 anesthetics over 7 years. Paediatr. Anaesth. 2018 Nov; 28(11): 1050–1058. PubMed Abstract | Publisher Full Text\n\nMondal RK, Mann U, Sharma M: Osteogenesis imperfecta with bleeding diathesis. Indian J. Pediatr. 2003 Jan; 70(1): 95–96. PubMed Abstract | Publisher Full Text\n\nHathaway WE, Solomons CC, Ott JE: Platelet function and pyrophosphates in osteogenesis imperfecta. Blood. 1972 Apr; 39(4): 500–509. PubMed Abstract | Publisher Full Text\n\nHumbert JR, Solomons CC, Ott JE: Increased oxidative metabolism by leukocytes of patients with osteogenesis imperfecta and of their relatives. J. Pediatr. 1971 Apr; 78(4): 648–653. PubMed Abstract | Publisher Full Text\n\nArmstrong D, VanWormer D, Solomons CC: Increased inorganic serum pyrophosphate in serum and urine of patients with osteogenesis imperfecta. Clin. Chem. 1975 Jan; 21(1): 104–108. PubMed Abstract | Publisher Full Text\n\nObaji S, Alikhan R, Rayment R, et al.: Unclassified bleeding disorders: outcome of haemostatic challenges following tranexamic acid and/or desmopressin. Haemophilia. 2016 Mar; 22(2): 285–291. Publisher Full Text\n\nKanakalakshmi ST: Assessment of perioperative bleeding in pediatric osteogenesis imperfecta patients undergoing orthopedic surgeries: A single-center study. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "363165",
"date": "05 Feb 2025",
"name": "Hesham Mohamed Elbaseet",
"expertise": [
"Reviewer Expertise Pediatric orthopedic surgeon specialized inosteogenesis imperfecta surgical treatment"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThanks for your effort in writing the manuscript. Please add and / or modify the following:\n1- A lot of cited references are out of date (one of them was 1971) please use recent references. 2- Mention whether osteotomies were done per cutaneous or open and explain why single osteotomy cases required blood transfusion. 3- Mention whether antifibrinolytic drugs were administrated or not? 4- Cite the following References in discussion part: [ref1].\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1420
|
https://f1000research.com/articles/13-890/v1
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06 Aug 24
|
{
"type": "Research Article",
"title": "Discrepancy in efficiency scores due to sampling error in data envelopment analysis methodology: evidence from the banking sector",
"authors": [
"Kishore L",
"Geetha E",
"Shivaprasad S P",
"Sachin R Chandra",
"Geetha E",
"Shivaprasad S P",
"Sachin R Chandra"
],
"abstract": "Background Data Envelopment Analysis (DEA) methodology is considered the most suitable approach for relative performance efficiency calculation for banks as it is believed to be superior to traditional ratio-based analysis and other conventional performance evaluations. This study provides statistical evidence on the sampling error that can creep into performance evaluation studies using the DEA methodology. Inferences are drawn based on samples, and various preventive measures must be taken to eliminate or avoid sampling errors and misleading results. This study demonstrates the possibility of sampling error in DEA with the secondary data available in financial statements and reports from a sample set of banks.\n\nMethods The samples included 15 public sectors and five leading private sector banks in India based on their market share, and the data for calculating efficiencies were retrieved from the published audited reports. The sample data was collected from 2014 to 2017 because the banking sector in India witnessed a series of mergers of public sector banks post-2017, and the data after that would be skewed and not comparable due to the demonetization policy implementation and merger process-related consolidation implemented by the Government of India. The efficiency measures thus computed are further analyzed using non-parametric statistical tests.\n\nResults We found statistically significant discrepancies in the efficiency score calculations using DEA approach when specific outlier values. Evidence is provided on statistically significant differences in the efficiencies due to the inclusion and exclusion of particular samples in the DEA.\n\nConclusion The study offers a novel contribution along with statistical evidence on the possible sampling error that can creep into the performance evaluation of organizations while applying the DEA methodology.",
"keywords": [
"Sampling Error",
"Performance Evaluation",
"Efficiency",
"Data Envelopment Analysis",
"Non-parametric Tests",
"Banking industry"
],
"content": "Introduction\n\nPerformance measurement and productivity improvement are vital for any organization as they help assess their performance and compare with benchmark organizations or set benchmarks to identify weak areas and opportunities for performance enhancement.1 Among the various performance indicators, efficiency is crucial and frequently used as an assessment tool against comparative benchmarks. Banks operate in a highly competitive market, and efficiency evaluation helps identify areas for improvement and develop sustainable strategies for performance enhancement, leading to a better competitive position in the industry. Financial ratio-based evaluation is adopted widely in performance assessment, which can be misleading as the benchmarks are arbitrary.2 This shortfall has increased the adoption of frontier performance evaluation methods across industries, including the banking sector.3,4 One commonly used non-parametric technique is Data Envelopment Analysis (DEA) in the banking industry. DEA is opined as the aptest approach for relative performance efficiency calculation for banks as DEA methodology is considered superior to traditional ratio-based analysis embraced for conventional performance evaluation.4 However, inferences drawn with DEA methodology based on samples can lead to possible sampling error.5,6 This study demonstrates the impact of such outlier samples that can skew the efficiency computed using DEA methodology with the secondary data available in financial statements and reports from a sample set of banks. The study offers a novel contribution along with statistical evidence on the possible sampling error that can creep into the performance evaluation of organizations while applying the DEA methodology.\n\nAs per DEA methodology, the efficiency of any service process or system can be computed as a ratio of output to input.7 Considering several inputs and outputs, the efficiency of each decision-making unit (DMU) can be written as\n\nThe model for efficiency computation considering the multiple outputs and multiple inputs based on the above is given by\n\nWhere “Em is the efficiency of the mth DMU”, “yjm is the output of the mth DMU”, “vjm is the weight of the output”, “xim is the input of the mth DMU”, “uim is the weight of the input” and “yjn and xin are the jth output and ith input”\n\nBased on the Linear Programming problem technique, DEA computes efficiency with two assumptions of return to scale - constant and variable,7 where constant return to the scale-based assumption of DEA is referred to as the overall technical efficiency. At the same time, variable returns to scale decompose overall technical efficiency into two components: pure technical efficiency and scale efficiency.8\n\nThe available literature on the discrepancies that can happen in DEA methodology is very scant. Those discussions on variation in performance efficiency are primarily about sample size and the possible interpretation errors during decision-making. Zhang & Bartels8 analyzed the variation in efficiency based on sample size using Monte Carlo Simulation. Using data from electricity distribution companies, they evaluated the efficiency and proved that the estimated mean technical efficiency decreases with increased sample size. The impact of sample size on the results of models involving non-discretionary variables was studied by Staat.8 Smith5 discussed the model misspecification in DEA, specifically when the sample size is insignificant. Banker and Chang8 discussed the procedure to detect and remove the outliers in the DEA approach. However, their approach was to remove selected observations or samples. However, the variation that can creep in due to the inclusion and exclusion of a specific set of samples is not considered. While Johnson & McGinnis6 focused on the mathematical model of inefficient outlier detection, Chen & Johnson9 developed a mathematical model to detect efficient and inefficient outliers in efficiency computation.\n\nThere is a significant amount of research on the performance evaluation of banks based on DEA.2–4,10–19 These prior studies have given insight into the efficiency of the performance of private and public sector banks in different contexts. These studies using DEA methodology have computed the efficiency based on the sample data collected from financial reports and published reports, and inferences are made according to the efficiency output from DEA methodology. However, the sampling error that can creep into performance evaluation studies using DEA methodology needs to be addressed, as it often gives misleading results regarding the efficiency of sample organizations under study. More precisely, which decision-making units under study must be chosen as the sample in the survey? The DEA methodology is a relative efficiency evaluation technique, and it will lead to misleading extrapolation when proper samples are not considered. Therefore, the problem statement framed is “Do sampling errors result in misleading results in performance evaluation using DEA methodology?\n\nThe study aims to critically analyze any significant difference in the efficiency scores due to the inclusion or exclusion of specific sample(s) in DEA methodology-based studies. State Bank of India (SBI) is the outlier to test the hypothesis, as stated below.\n\n“There is no significant difference in the average efficiency scores between the two groups, SBI included and excluded, respectively.”\n\n“There is a significant difference in the average efficiency scores between the two groups, SBI included and excluded, respectively.”\n\n\nMethods\n\nThe performance efficiency scores of banks are calculated using DEA methodology.20 The study sample comprises 20 selected banks in India, which include fifteen public sector and five leading private sector banks based on their market share. The data for analysis for all 20 banks were retrieved from the published audited reports and Profit & Loss statements of banks available on the respective bank websites.21 The period of data collected is from 2014 to 2017 for all the 20 banks selected, which is before the demonetization policy implementation by the Government of India22 and before the mergers of many public sector banks in India23 so that the effects of such a major national-level policy implementation and mergers do not have any impact on the data analysis. Overall technical efficiency based on DEA methodology was computed with the input variables as total and employee expenses and net Non-Performing-Assets (NPAs), considering the two critical variables per the literature review: total income and operating profit as outputs. Efficiency was computed in two groups, with one group of DMUs including SBI (State Bank of India) and another group excluding SBI. SBI is selected for comparison sample as the values of all the variables for SBI considered in the study indicate it as an outlier and, hence, the most suitable sample to compare. The results were analyzed to study the efficiency distribution after the computation of performance efficiency scores of the DMUs. Further, the Mann-Whitney U test is adopted to test the differences in the average distribution between the two groups.24 The free version of the DEAFrontier tool24 was used to calculate efficiency scores using DEA methodology, and the open-source R programming software was used to perform the non-parametric hypothesis test. Data visualization was performed using Python open-source programming software.\n\n\nResults and Discussion\n\nThe performance efficiency score was calculated using DEA methodology, with the SBI sample included and later excluded for comparative analysis. The histogram showing the performance efficiency of the samples – with SBI included and SBI excluded, as shown in Figure 1 and Figure 2, respectively, indicates that the efficiency scores are not normally distributed. The box plot for the performance efficiency scores, with SBI included and SBI excluded, shown in Figure 3, also confirms that the efficiency scores are not normally distributed.\n\nShapiro-Wilk Test is performed to check for normal data distribution, and the test results are shown in Table 1. W-static and p-value for both SBI included and excluded confirm that the distributions are not typical. Skewness and Kurtosis measures also indicate that the efficiency of samples with SBI included having negatively skewed distribution and without SBI included as positively skewed.\n\nSince the data is abnormal, non-parametric tests are applied to test the hypothesis. The results of the Mann-Whitney U test for independent samples test are shown in Table 2. The p-value is almost equal to 0 at a 0.05 significance level.\n\nInterpreting from Table 2, we can reject Ho, indicating that there is a statistically significant difference in efficiency distribution between the performance efficiency calculated with SBI included and excluded. Wilcoxon signed-rank test with continuity correction25,26 was also performed to test the following hypothesis:\n\n“There is no significant difference in the efficiency score calculated with SBI included and excluded.”\n\n“There is a significant difference in the efficiency score calculated with SBI included and excluded.”\n\nThe p-value is almost 0 and is <0.05. Therefore, we fail to accept Ho, indicating a statistically significant difference in efficiency values computed with SBI and without SBI being considered in the sample. Spearman’s rank and Kendall Tau correlation tests are also conducted with the following hypotheses to increase the power of a statistical test.\n\n“There is no association between the efficiency values”\n\n“There is a significant association between the efficiency values”\n\nAccording to Spearman’s rank correlation test, the p-value is almost 0.3671 and >0.05. Also, rho is very negligible, 0.06. Therefore, we fail to reject Ho, indicating no statistically significant association between the efficiency values computed with SBI and those without SBI being considered in the sample. Per the Kendall Tau correlation test, the p-value is almost 0.3165 and >0.05. Also, tau is very negligible, 0.048. Therefore, we fail to reject Ho, indicating no statistically significant association between the efficiency values computed with SBI and those without SBI being considered in the sample. The correlation plot and bar diagram shown in Figure 4 and Figure 5, respectively, also confirm the absence of any association between the efficiency values computed with SBI and those without SBI being considered in the sample.\n\nTherefore, inclusion and exclusion of a sample result in significant variation in the efficiency computed, which in statistical terms is sampling error. Blind consideration of sample units for performance efficiency computation will result in misleading results, flawed interpretations, and erroneous decisions. Before calculation of efficiency using DEA methodology, the box-and-whisker plot for one of the variable Employee Expenses with the outlier SBI included, as shown in Figure 6, along with basic descriptive statistical measures, can help to identify the outliers that can result in efficiency computation errors due to sampling. The box-and-whisker with SBI excluded, as shown in Figure 7, shows how the variables are distributed in a range that allows comparison and efficiency evaluation to be more realistic.\n\n\nConclusion\n\nThe relative efficiencies were calculated in two groups; one group included SBI as a DMU, and the other excluded SBI. The efficiencies thus calculated were tested for significant change in the average efficiency between the groups. The study provides statistical evidence on the sampling error that can creep into performance evaluation studies' DEA methodology. In practice, inferences were made based on samples, and various preventive measures must be taken to eliminate or avoid sampling error and related misleading results. The study offers a novel contribution along with statistical evidence on the possible sampling error that can creep into the performance evaluation of organizations due to the inclusion or exclusion of specific samples in the relative performance evaluation computation using DEA. The study also discussed how box-and-whisker can help quickly to identify the possible outlier that can cause skewed efficiency scores due to sampling error. The study was limited only to major and selected sample banks. Future studies can consider all types of banks to get a holistic picture of the banking industry performance benchmark and outlier impacts. Future studies can adopt other relevant non-parametric tests and thus increase the statistical power to confirm the findings.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nThe underlying data of the variables used for performance efficiency score calculation is taken from the audited reports of banks published on the respective bank websites and accessible to the public since the sample companies are registered and listed. For example, the data of SBI Bank is available in the PDF format reports published in the link https://sbi.co.in/web/investor-relations/reports. The user can navigate and select the appropriate year to download the reports in PDF format and retrieve data as required. The links for accessing other sample banks are given below.\n\nhttps://www.canarabank.com/pages/audited-and-unaudited-financial-results\n\nhttps://www.iob.in/Financial_perf\n\nhttps://karnatakabank.com/investors/quarterly-results\n\nhttps://ucobank.com/financial-results-2014-15\n\nhttps://centralbankofindia.co.in/en/node/219217\n\nhttps://www.idbibank.in/idbi-bank-analyst-presentation.aspx\n\nhttps://www.unionbankofindia.co.in/english/financial-result.aspx\n\nhttps://bankofindia.co.in/financial-result\n\nhttps://www.bankofbaroda.in/shareholders-corner/financial-reports/financial-report-q4-2022-23\n\nhttps://www.hdfcbank.com/personal/about-us/investor-relations/financial-results\n\nhttps://www.icicibank.com/about-us/qfr\n\nhttps://www.axisbank.com/shareholders-corner/financial-results-and-other-information/quarterly-results\n\nhttps://www.kotak.com/en/investor-relations/financial-results/quarterly-results.html?source=website\n\nhttps://www.yesbank.in/about-us/investor-relations/financial-information/financial-results\n\nFor easy access, the data collected from the reports of all the sample banks considered for the study are consolidated and made available in the Figshare repository per the details below.\n\nFigshare: Audited reports data, https://doi.org/10.6084/m9.figshare.26046277. 27\n\nThis project contains the following data:\n\n• Audited reports data in xlsx file format containing the data required for analysis taken from the banks website. Audited reports data” file contains all the data taken from audited reports that are required for analysis.\n\n• Quarterly performance efficiency scores calculated based on the data from audited reports. “Quarterly efficiency score” file contains the calculated performance efficiency scores using DEAFrontier software.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nSaxena P, Saxena RR, Sehgal D: Efficiency evaluation of the energy companies in CNX 500 Index of the NSE, India using data envelopment analysis. Benchmarking. 2016; 23(1): 113–126. Publisher Full Text\n\nSathye M: Efficiency of banks in a developing economy: The case of India. Eur. J. Oper. Res. 2003; 148(3): 662–671. Publisher Full Text\n\nRay SC, Das A: Distribution of cost and profit efficiency: Evidence from Indian banking. Eur. J. Oper. Res. 2010; 201(1): 297–307. Publisher Full Text\n\nSaha A, Ravisankar TS: Rating of Indian commercial banks: a DEA approach. Eur. J. Oper. Res. 2000; 124(1): 187–203. Publisher Full Text\n\nSmith P: Model misspecification in Data Envelopment Analysis. Ann. Oper. Res. 1997; 73: 233–252. Publisher Full Text\n\nJohnson AL, McGinnis LF: Outlier detection in two-stage semiparametric DEA models. Eur. J. Oper. Res. 2008; 187(2): 629–635. Publisher Full Text\n\nCharnes A, Cooper WW, Rhodes E: Measuring the efficiency of decision making units. Eur. J. Oper. Res. 1978; 2(6): 429–444. Publisher Full Text\n\nStaat M: The Effect of Sample Size on the Mean Efficiency in DEA: Comment. J. Prod. Anal. 2001; 15(2): 129–137. Publisher Full Text\n\nChen W-C, Johnson AL: A unified model for detecting efficient and inefficient outliers in data envelopment analysis. Comput. Oper. Res. 2010; 37(2): 417–425. Publisher Full Text\n\nGeetha E, Kishore L, Shivaprasad SP: Quarterly performance benchmarking of Selected Banks in India - A DEA approach. Int. J. Pure Appl. Math. 2017; 117(20). Special Issue.\n\nGulati R, Kumar S: Assessing the impact of the global financial crisis on the profit efficiency of Indian banks. Econ. Model. 2016; 58: 167–181. Publisher Full Text\n\nBapat D: Efficiency for Indian public sector and private sector banks in India: Assessment of impact of global financial crisis. Int. J. Bus. Perform. Manag. 2012; 13(3–4): 330–340. Publisher Full Text\n\nPuri J, Yadav SP: Performance evaluation of public and private sector banks in India using DEA approach. Int. J. Oper. Res. 2013; 18(1): 91–121. Publisher Full Text\n\nNarayanaswamy T, Muthulakshmi AP: Productivity and cost efficiency of commercial banks in India. Indian J. Financ. Jan. 2016; 10(1): 8–27. Publisher Full Text\n\nKumar S, Raina S: Performance measurement of Indian banking sector: a cross-section perspective. International Journal of Business and Globalisation. 2024; 37(2): 210–236. Publisher Full Text\n\nKaur J, Pathak N, Aggarwal S: Data Envelopment Analysis (DEA) in measuring the performance of public sector banks in India. Sustainability and Equity: Economic Democracy and Social Empowerment. Jan. 2024; pp. 231–243.\n\nKhan A, Ahmad A, Shireen S: Ownership and performance of microfinance institutions: Empirical evidences from India. Cogent Econ. Financ. 2021; 9(1). Publisher Full Text\n\nVenugopal SK: Loan Portfolio Management and Bank Efficiency: A Comparative Analysis of Public, Old Private, and New Private Sector Banks in India. Economies. Apr. 2024; vol. 12(4): Publisher Full Text\n\nKumar S, Gulati R: Evaluation of technical efficiency and ranking of public sector banks in India: An analysis from cross-sectional perspective. Int. J. Product. Perform. Manag. 2008; 57(7): 540–568. Publisher Full Text\n\nCharnes A, Cooper WW, Rhodes E: Measuring the efficiency of decision making units. Eur. J. Oper. Res. 1978; 2(6): 429–444. Publisher Full Text\n\nAudited reports data. Accessed: Jun. 16, 2024. Reference Source\n\nRajendra Kumar R: Demonitization and its effect on life of common people in India. Indian J. Econ. Dev. 2016; 4(11).\n\nSingh S, Das S: Impact of post-merger and acquisition activities on the financial performance of banks: A study of Indian private sector and public sector banks. Espacios. 2018; 39(26).\n\nDEA Software. Accessed: Jun. 13, 2024. Reference Source\n\nHollander M, Wolfe DA, Chicken E: Nonparametric statistical methods.2015. Publisher Full Text\n\nWilcoxon F: Individual Comparisons by Ranking Methods. Biom. Bull. Dec. 1945; 1(6): 80. Publisher Full Text\n\nKishore L, Shivaprasad SP, Geetha E: Audited reports data. [Dataset]. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "325798",
"date": "30 Sep 2024",
"name": "Katerina Fotova Čiković",
"expertise": [
"Reviewer Expertise Finance",
"banking sector",
"M&A",
"DEA"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe topic is well formulated, relevant to the area of interest and related to an important and current subject on global level. The abstract is well worded and provides a short, clear and effective introduction to the paper. Methodology is extensively introduced and each step of the process is presented. There are too many figures. I wonder if they are all beneficial? However, there is a need for sample clarification. How did you come up with this sample? What was the selection process of the banks entering the sample? The analyzed period is somewhat questionable (it is a period almost 7 years ago, and it may not be relevant anymore). Do not use \"we\", \"our\" in the text. Instead, use 3rd person singular.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12542",
"date": "01 Oct 2024",
"name": "Kishore L",
"role": "Author Response",
"response": "How did you come up with this sample? What was the selection process of the banks entering the sample? Response to the above 2 query: The study sample comprises 20 selected banks in India, which include fifteen public sector and five leading private sector banks. This was done to have representation of public as well as private sector banks in the same. And therefore, as mentioned in the methodology section which I quote \" The study sample comprises 20 selected banks in India, which include fifteen public sector and five leading private sector banks based on their market share\", the selection was based on their market share. Hope the explanation is satisfactory. The analyzed period is somewhat questionable (it is a period almost 7 years ago, and it may not be relevant anymore). Response to the above query: The period of data collected is from 2014 to 2017 for all the 20 banks selected. This period was selected because there was two national-level major policy implemented in India - one on Demonetization and another was the merger of many banks. Due to demonetization and mergers there was an overhaul in the banks and also after the mergers the balance sheet is consolidated due to which the data after these policy implementations will not be suitable to empirically prove our hypothesis. And therefore, as mentioned in the methodology section which I quote \"The period of data collected is from 2014 to 2017 for all the 20 banks selected, which is before the demonetization policy implementation by the Government of India [23] and before the mergers of many public sector banks in India [24] so that the effects of such a major national-level policy implementation and mergers do not have any impact on the data analysis\", we decided to use the data before these major reforms. Hope the explanation is satisfactory. Do not use \"we\", \"our\" in the text. Instead, use 3rd person singular. Response to the above suggestion: Completely agree to your suggestion. The correction will be incorporated in the revision. Thanks for the review."
}
]
},
{
"id": "325801",
"date": "09 Oct 2024",
"name": "Weng Hoe Lam",
"expertise": [
"Reviewer Expertise Statistical modeling",
"Operations Research"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study offers a novel contribution along with statistical evidence on the possible sampling error that can creep into the performance evaluation of organizations while applying the DEA methodology. Kindly refer to the following comments for improvement. 1)Please include the managerial and policy implications section 2)Please include the state-of-the-art table in the literature review section to show the research gap\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12594",
"date": "10 Oct 2024",
"name": "Kishore L",
"role": "Author Response",
"response": "Dear reviewer, Thanks for the review and comments. We will include implications in addition to tabulating the literature review highlighting the gap in the revision. Thanking once again. Regards Kishore L"
}
]
}
] | 1
|
https://f1000research.com/articles/13-890
|
https://f1000research.com/articles/13-1416/v1
|
25 Nov 24
|
{
"type": "Research Article",
"title": "Autonomizing Public Universities in Ethiopia: Exploring the Potential Challenges",
"authors": [
"Awol Ali Mohammed"
],
"abstract": "Background This study examines the challenges faced by Ethiopian public universities in achieving institutional, administrative, academic, and financial autonomy. Institutional autonomy refers to a university’s ability to self-govern, set its mission, and establish policies without external interference. Administrative autonomy concerns decision-making in operations, academic autonomy relates to academic freedom and quality assurance, and financial autonomy involves control over resources and revenue generation. In Ethiopia, centralized governance, political interference, and limited financial strategies create significant barriers to autonomy.\n\nMethod A qualitative research approach was employed, utilizing semi-structured interviews, key informant interviews, focus group discussions, and direct observations. Data were collected from 59 participants across three public universities. Tools included consent forms, interview guides, focus group discussion guides, and observation checklists. Thematic analysis was used to identify key patterns in the autonomy challenges. The study is grounded in Institutional Theory, Principal-Agent Theory, and Resource Dependency Theory.\n\nResult The findings indicate that institutional autonomy is constrained by centralized governance and political interference, limiting universities’ ability to make independent decisions, as explained by Institutional Theory. Administrative autonomy faces similar restrictions, with decision-making influenced by external entities, as highlighted by Principal-Agent Theory. Academic autonomy is challenged by the tension between standardization and institutional diversity, particularly in quality assurance and accreditation. Financial autonomy is limited by restricted revenue sources, economic instability, and a lack of innovative funding strategies, as discussed through Resource Dependency Theory.\n\nConclusion The study concludes that Ethiopian public universities face significant barriers to autonomy. Addressing these challenges requires reducing strict governmental control, improving governance structures, and promoting independent decision-making and sources of incomes.\n\nRecommendations The study recommends implementing governance reforms, providing leadership training for university administrators, enhancing academic freedom with flexible quality assurance systems, and diversifying revenue streams through partnerships and expanded university enterprises to ensure financial sustainability.",
"keywords": [
"Public-universities",
"Administrative-autonomy",
"Academic-autonomy",
"Financial-autonomy",
"Ethiopia"
],
"content": "1. Introduction\n\nSince the late twentieth century, the landscape of higher education (HE) has undergone a profound transformation, characterized by rapid expansion, increasing complexity of higher education institutions (HEIs), and the emergence of a knowledge-based global economy. This evolution has prompted states to grant greater autonomy to HEIs, resulting in a marked reduction in state regulation and an increase in institutional independence (Marmolejo, 2016). In contemporary higher education, a global consensus is emerging regarding the necessity of institutional autonomy as a means to enhance competitiveness, foster innovation, and support economic development. Autonomy is increasingly viewed as essential for protecting academic freedom, improving institutional efficiency, promoting knowledge transmission, and achieving modernization goals (Maassen et al., 2017).\n\nThe discourse surrounding institutional autonomy has gained substantial traction in recent years, as countries recognize its critical role in facilitating effective competition and fostering intellectual discovery within a knowledge-based society (Altbach et al., 2011; Maassen, 2000). Autonomy has become a central tenet of national higher education reform agendas, as exemplified by Germany’s pre-1989 reform initiatives aimed at enhancing institutional independence (Kehm, 2014). The acknowledgment of autonomy’s importance reflects its multifaceted significance, which ranges from fostering competitiveness to safeguarding academic integrity (Judith & Stamenka, 2021). However, the challenges faced by universities—including massification, reduced public funding, market competition, and evolving economic demands—underscore the complexities inherent in the pursuit of autonomy (Altbach et al., 2011).\n\nThe modern university, much like the societies it inhabits, is undergoing significant transformation driven by rapid changes and globalization (Sunandar & Imron, 2019). The 1998 UNESCO World Conference underscored that academic freedom and institutional autonomy are fundamental conditions for universities, reinforcing their role as bastions of scholarship and learning. Autonomy encompasses the authority to determine curriculum content, teaching methodologies, and student admission criteria, thereby enabling institutions to shape educational programs and policies (Kezar, 2013). It stands as a cornerstone of higher education, ensuring that universities can uphold their scholarly missions and contribute meaningfully to society (Aithal & Kumar, 2019).\n\nIn the contemporary landscape of higher education, the concepts of administrative, academic, and financial autonomy are crucial for fostering institutional resilience, enhancing competitiveness, and ensuring effective governance. Administrative autonomy refers to the capacity of higher education institutions (HEIs) to manage their internal operations independently of external governmental interference. This includes the authority to make decisions regarding staffing, organizational structure, and institutional policies, allowing universities to respond promptly and effectively to their unique challenges and opportunities (Kezar, 2013). A high degree of administrative autonomy enables HEIs to cultivate an environment that prioritizes innovation, efficiency, and responsiveness to the needs of students and faculty alike (Gonzalez & de Silva, 2018).\n\nAcademic autonomy, on the other hand, encompasses the freedom of institutions to define their educational programs, curricula, teaching methodologies, and research agendas. This form of autonomy is vital for preserving academic freedom, fostering intellectual inquiry, and promoting the diversity of thought that is essential in a globalized knowledge economy (Boyer, 1990; Hemsley-Brown & Oplatka, 2015). When universities possess academic autonomy, they can better adapt their offerings to evolving societal and labor market demands, thus enhancing their relevance and impact (Trow, 1996). Moreover, academic autonomy empowers faculty members to engage in research and scholarship without undue pressure from political or ideological constraints, ultimately contributing to the advancement of knowledge (Guri-Rosenblit, 2009).\n\nFinancial autonomy pertains to the ability of HEIs to generate and manage their financial resources independently. This autonomy is fundamental for ensuring institutional sustainability, allowing universities to diversify their funding sources, including tuition fees, grants, donations, and partnerships with industry (Johnstone, 2003). With greater financial autonomy, universities can invest in infrastructure, enhance educational quality, and support research initiatives that align with their strategic objectives (Salmi, 2003). Financial autonomy not only enables institutions to withstand fluctuations in government funding but also fosters a culture of accountability and transparency in resource allocation (Johnstone, 2003).\n\nCollectively, administrative, academic, and financial autonomy form the bedrock of an effective and responsive higher education system. These interrelated dimensions of autonomy not only empower universities to fulfill their mission of teaching, research, and community engagement but also position them as key players in addressing global challenges and contributing to societal advancement. As countries around the world grapple with the complexities of higher education governance, understanding and fostering these forms of autonomy will be essential for promoting institutional excellence and resilience in an increasingly competitive landscape.\n\nDespite these global trends, the level of administrative, academic, and financial autonomy in Ethiopian universities remains notably constrained when compared to many European counterparts (Mekonnen et al., 2022). Ethiopia’s governance model is predominantly “state-centered,” which contrasts with the global shift toward “state supervision” or “steering from a distance” (Gebru et al., 2020). Although Ethiopian higher education institutions are legally designated as autonomous entities, the state retains substantial influence, often manifesting in limited academic and administrative freedom (Aboye, 2021).\n\nEthiopia’s higher education system presents a compelling case study due to its simultaneous growth and the challenges it faces. Over the past two decades, the number of public universities has increased from two to 45, and private institutions have surged to 221 (The Reporter, 2023). This rapid expansion poses challenges for effective state oversight and regulation (Mekonnen et al., 2022). The systemic issues within Ethiopian higher education—pertaining to academic, administrative, and financial constraints—have contributed to the relatively low performance of its institutions (Akalu, 2014).\n\nAchieving university autonomy in Ethiopia is fraught with challenges spanning historical, political, economic, and social domains. The governance framework heavily influenced by the state has long constrained academic and administrative freedom, stifling innovation and responsiveness to academic and societal needs. Centralized control has led to politicization of university leadership and interference in academic affairs, undermining the principles of academic freedom and institutional autonomy (Getu, 2021; Gebru et al., 2020). Addressing these challenges necessitates a shift toward a more decentralized governance model that empowers universities to exercise genuine autonomy in all aspects of their operations.\n\nIn light of the pursuit of academic excellence, the recent government initiative to grant administrative, academic, and financial autonomy to public universities represents a significant shift. However, the historical context of centralized control and dependency on government funding poses considerable obstacles to realizing full autonomy (Abebaw, 2021). This study aims to explore the potential hurdles faced by Ethiopian public universities in their pursuit of autonomy, focusing specifically on administrative, academic, and financial dimensions.\n\nThe necessity of studying the transition toward autonomy in Ethiopian public universities is underscored by the multifaceted challenges and paradoxes inherent in this process. Understanding the intricacies of this transition is crucial for enhancing the overall quality and accessibility of education as the country moves toward decentralized decision-making and self-governance in its higher education institutions. A qualitative research approach will facilitate a comprehensive examination of these issues, integrating primary and secondary data sources for a holistic understanding of the challenges faced by Ethiopian universities.\n\nSeveral studies have explored various aspects of higher education in Ethiopia, such as expansion, quality assurance, institutional autonomy, and challenges. For example, Akalu (2014) discussed the expansion and quality assurance of higher education in Ethiopia, while Aboye (2021) examined the perils and promises of university autonomy. Getu (2021) focused on the accountability practices of Ethiopian first-generation public universities, and Gebru et al. (2020) applied the European University Autonomy Scorecard Methodology to assess institutional autonomy in Ethiopian public universities. Getu (2021) addressed challenges and proposed solutions for higher education in Ethiopia, and Aithal & Aithal (2019) discussed autonomy as a means to achieve excellence in universities. Getu (2021) explored institutional autonomy mechanisms in the case of Adama Science and Technology University, while Aboye (2021) examined the relationship between political ideology and academic autonomy in Ethiopia.\n\nHowever, none of these studies specifically addressed the challenges of the recent initiative to grant autonomy to universities in Ethiopia, spearheaded by the current government. Therefore, this study aims to fill this gap by providing a comprehensive analysis of the potential challenges of autonomizing universities in Ethiopia. This research represents a novel endeavor, starting from scratch to explore this critical topic. One of the critical gaps in the previous studies is the lack of attention to the potential challenges of administrative, academic and financial challenges of university autonomization in Ethiopia.\n\nTherefore, this study endeavors to address this lacuna by conducting a comprehensive analysis of the envisaged impediments and prospects associated with administrative, academic and financial autonomization of universities in Ethiopia. Integral to this endeavor is an exploration of the implications of institutional autonomy on key domains, including but not limited to, governance structures, academic liberties, and financial administration. Additionally, the study undertakes an examination of the projected ramifications on educational accessibility, equity, and standards. Specifically, this study aims to:\n\n• Examine the challenges associated with institutional autonomy in the selected public universities.\n\n• Identify the key obstacles to administrative autonomy in the selected public universities.\n\n• Evaluate the issues surrounding academic autonomy in the selected public universities.\n\n• Assess the challenges related to financial autonomy in the selected public universities.\n\n\n2. Theoretical framework\n\nThis study employs three relevant theories to critically discuss the objectives of examining administrative, academic, and financial autonomy in Ethiopian public universities. As these institutions seek greater autonomy, they face multiple challenges rooted in governance structures, resource dependencies, and institutional norms. Administrative autonomy is constrained by centralized control, academic autonomy by standardized policies, and financial autonomy by limited funding sources. To explore these dimensions comprehensively, Principal-Agent Theory, Resource Dependency Theory, and Institutional Theory offer a robust theoretical framework to analyze the key challenges and opportunities associated with university autonomy.\n\nPrincipal-Agent Theory (PAT) examines the relationship between a principal (authority) and an agent (subordinate), where the agent is entrusted to act on behalf of the principal. However, conflicts often arise because the agent may have different goals or preferences than the principal, leading to issues of trust, accountability, and control. In the context of university autonomy, the government acts as the principal, overseeing public universities, while the universities function as agents tasked with carrying out academic, administrative, and financial responsibilities.\n\nFor administrative autonomy, PAT is crucial in understanding the complexities of delegating decision-making powers to universities. Governments in many countries, including Ethiopia, often exercise significant control over public institutions due to concerns about accountability, national standards, and equity. This can result in universities having limited freedom to govern themselves. The theory suggests that to enhance administrative autonomy, universities must demonstrate that they can align their internal goals with the broader policy objectives of the state while maintaining operational independence (Shattock, 2019). However, political interference, bureaucratic regulations, and the legacy of centralized governance in Ethiopia continue to hamper universities’ ability to self-govern. By applying PAT, the study can examine how shifting more decision-making power to universities—while ensuring mechanisms for accountability—might lead to better governance and innovation within Ethiopian public universities.\n\nIn terms of academic autonomy, PAT also helps explore the extent to which universities can set their own academic standards, develop curricula, and manage quality assurance. The principal (government) often imposes rigid accreditation standards and curricular frameworks, which may conflict with universities’ desire for academic freedom and innovation. This tension can be analyzed through PAT by exploring how universities negotiate the balance between fulfilling government mandates and pursuing independent academic goals (Shattock, 2019).\n\nResource Dependency Theory (RDT) posits that organizations are dependent on external resources for their survival, and this dependency shapes their decisions, strategies, and autonomy. Universities, as organizations, are reliant on financial resources from the government, donors, and, in some cases, tuition fees. In the Ethiopian context, public universities are primarily funded by the state, which creates a dependency that limits their financial autonomy.\n\nRDT is highly relevant for understanding the financial autonomy of Ethiopian universities because it emphasizes how financial dependence on the government restricts institutional flexibility. Universities that depend heavily on government funding often face tight controls over how funds are allocated and spent, which can hinder their ability to make independent financial decisions (Pfeffer & Salancik, 2003). For example, limited access to diversified revenue streams forces universities to comply with governmental priorities, limiting their ability to invest in innovative research, infrastructure, or program expansion. The study could apply RDT to explore how Ethiopian universities might overcome these limitations by developing alternative sources of revenue, such as industry partnerships, alumni donations, or income-generating programs (Bourgeois & Nizet, 2019).\n\nThe theory also highlights the importance of strategic alliances and collaborations to mitigate resource dependency. In the case of Ethiopian universities, RDT can help analyze potential partnerships with international organizations or private sectors that could reduce their overreliance on state funding, allowing for more independent financial decision-making and, consequently, more autonomy.\n\nInstitutional Theory focuses on how organizations are influenced by the institutional environments in which they operate. It suggests that organizations are shaped by formal structures, cultural norms, and external pressures, which can either promote or constrain their autonomy. This theory is particularly useful for examining both administrative and academic autonomy within Ethiopian public universities.\n\nFor administrative autonomy, Institutional Theory helps explain how universities are embedded in a broader governance framework shaped by governmental policies, legal structures, and historical norms. In Ethiopia, universities have long been subject to centralized control, which is reinforced by institutional norms and expectations about state oversight. This institutionalized centralization can limit the scope for universities to develop their own governance systems, as deviations from government-prescribed practices are often seen as noncompliant or inefficient (DiMaggio & Powell, 1983). Institutional Theory allows the study to explore how universities can navigate these constraints and carve out spaces for autonomy while remaining compliant with national and regulatory standards. It also sheds light on the cultural and political barriers that may hinder the decentralization process, such as resistance from established bureaucratic institutions.\n\nIn the case of academic autonomy, Institutional Theory highlights how external forces, such as accreditation bodies, quality assurance agencies, and international rankings, shape academic policies and decision-making within universities. These external pressures often force universities to conform to standardized models of academic governance, even when such models may not align with the institution’s specific needs or goals (Meyer & Rowan, 1977). For Ethiopian universities, this means that while they may aspire to greater academic freedom, they are constrained by the need to meet externally imposed standards, such as those related to curriculum development and faculty qualifications. Institutional Theory can help explore how Ethiopian universities might balance the demands for academic conformity with their desire for innovation and flexibility in teaching and research.\n\n\n3. Methods\n\nThis study is designed to be conducted at the national level with specific limitations. To enhance manageability and facilitate meaningful comparisons of results, as well as to derive valuable insights and findings that can be applied to other universities across the country, the study focuses on three first-generation universities. These universities, namely Addis Ababa University, Hawassa University, and Arba Minch University, have been purposefully selected for several reasons, including their roles in the first and second phases of public university autonomy in Ethiopia.\n\nAddis Ababa University (AAU), established in 1950 as the University College of Addis Ababa (UCAA), stands as Ethiopia’s oldest and largest institution for higher learning and research. Over the years, AAU has been a leading center for teaching, research, and community services. From a modest beginning with 33 students in 1950, AAU now boasts a student body of 48,673 (including 33,940 undergraduates, 13,000 master’s students, and 1,733 PhD candidates) and a staff of 6,043 (comprising 2,408 academics and 3,635 support staff ). The university offers 70 undergraduate and 293 graduate programs across its 14 campuses, including 72 PhD and 221 master’s programs. Since its inception, AAU has witnessed over 222,000 graduates (AAU Official Website, 2023).\n\nHawassa University (HU) has its origins in the mid-1970s with the establishment of “Awassa College of Agriculture” (ACA) in 1976, and it became a full-fledged university in 1999. Prior to this transformation, ACA was part of Debub University, which also included two other colleges: Wondo Genet College of Forestry (established in 1978) and Dilla College of Teacher Education and Health Sciences. In 1999, these institutions merged to form Hawassa University. As of 2018/19, HU comprises two institutes and eight colleges, spread across seven campuses. The university serves more than 40,000 students in regular, continuing, and distance education programs, offering a wide array of undergraduate, postgraduate, and PhD programs (HU Official Website, 2023).\n\nAt the moment, Hawassa University (HU) is one of the first-generation universities in Ethiopia encompassing 9 colleges, 3 institutes, and 7 campuses set in and outside of Hawassa City. Hawassa University in Ethiopia comprises several colleges, each offering various academic programs (Hawassa University Official Website, 2023). College of Agriculture, College of Business and Economics, College of Computing and Informatics, College of Education and Behavioral Sciences, College of Engineering, College of Medicine and Health Sciences, College of Natural and Computational Sciences, College of Social Sciences and Humanities and college of Law and Governance.\n\nArba Minch University (AMU) is a national university located in Arba Minch, within the Southern Nations, Nationalities, and Peoples’ Region of Ethiopia. Its roots can be traced back to the Arba Minch Water Technology Institute, established in September 1986 and later transferred from the Water Resource Commission to the Ministry of Education in 1993. The official establishment of Arba Minch University took place on September 20, 2004, following a government proclamation (Council of Ministers 111/2004). Initially composed of the Water Technology Institute, Faculty of Engineering, Faculty of Science, Faculty of Social Science and Humanities, Faculty of Business and Economics, and the School of Graduate Studies, AMU now offers a diverse array of 74 undergraduate programs, 115 graduate programs, and 27 PhD programs. The university is organized into three institutes, six colleges, and four schools, each distributed across its six campuses: Main Campus, Abaya Campus, Chamo Campus, Kulfo Campus, Nech Sar Campus, and Sawla Campus (AMU Official Website, 2023).\n\n3.1.1 Research Design and Approach\n\nThe study employed a descriptive research design to explore the challenges associated with achieving autonomy in Ethiopia’s public universities. This approach allowed for a detailed examination of the administrative, academic, and financial obstacles faced by these institutions, utilizing qualitative data from interviews, focus group discussions, and observations (Creswell, 2014).\n\nIn the study, a combination of qualitative data collection methods—including semi-structured interviews, key informant interviews, focus group discussions (FGDs), observations, and document analysis—were employed to address the research questions on institutional autonomy in public universities. Each method was strategically selected to align with the specific research questions, ensuring a comprehensive understanding of the perceptions and challenges surrounding institutional autonomy in the selected universities.\n\nSemi-structured interviews and key informant interviews were used to examine the perceptions of universities regarding institutional autonomy, focusing on both expectations and the actual realities experienced. Semi-structured interviews allowed for the exploration of personal insights, capturing the nuanced perspectives of individual participants, such as university faculty and administrative staff, regarding their expectations of autonomy and the actual practices observed in their institutions. Key informant interviews targeted high-ranking officials, policymakers, and experts knowledgeable about governance structures and policies influencing institutional autonomy. These interviews provided valuable insights into the decision-making processes and the broader institutional context, facilitating a deeper understanding of how autonomy was conceptualized and operationalized in practice.\n\nFocus group discussions (FGDs) were employed to evaluate the challenges related to academic autonomy in the selected public universities. FGDs encouraged group interaction and allowed participants to reflect on shared experiences and concerns. Faculty members and students, as key stakeholders in academic autonomy, participated in these discussions. The collective nature of FGDs facilitated the identification of common themes and challenges faced by different participants, promoting a more holistic understanding of the barriers to academic freedom and autonomy within the university setting. For the interviews and focus group discussions (FGDs), the researcher utilized interview guide to articulate the data collection process (Mohammed, 2024).\n\nObservations were conducted to identify the challenges related to administrative autonomy. By observing the day-to-day administrative processes and decision-making practices, the researcher gained firsthand insights into how autonomy was exercised in practice. Observations allowed the researcher to assess the extent of administrative decentralization, the level of involvement of different university actors in decision-making, and the constraints imposed by external bodies such as government agencies. This method provided a practical and grounded understanding of the challenges hindering effective administrative autonomy. Additionally, observation checklists were employed for the direct observations to ensure a systematic and comprehensive assessment of the phenomena under study (Mohammed, 2024).\n\nDocument analysis was essential for examining the challenges related to financial autonomy in the selected public universities. The method involved the systematic review of financial reports, policy documents, university budgets, and other relevant documentation that shed light on the financial governance and autonomy of universities. By analyzing these documents, the researcher identified patterns in funding allocation, decision-making authority regarding financial resources, and the financial constraints faced by universities. This approach was crucial for understanding the broader financial context in which public universities operated and the extent to which financial autonomy was realized or constrained. Table 1 shows the equal representation of participants from the three universities, along with the inclusion of Ministry of Education officials.\n\nObservations were made on academic, administrative, and budget plans using standardized checklists. Document analysis focused on university autonomy guidelines, reports, and administrative and teaching-learning facilities to diversify data sources and gain a comprehensive understanding of the situation.\n\nData management focused on ensuring quality assurance through integrated systems for data collection, cleaning, storage, and monitoring (Gibbs, 2018). Cross-referencing interviews with documents also played a key role in verifying the reliability of the data (Yin, 2018). Participants were given detailed explanations of the research questions to ensure clarity and facilitate meaningful responses (Silverman, 2020; Yin, 2018).\n\nThe qualitative data collected for this study were analyzed using a combination of thematic and comparative techniques. Specifically, Braun and Clarke’s (2006) six-step thematic analysis approach was adopted, which involves the following stages: (1) familiarization with the data through repeated reading, (2) generating initial codes by identifying relevant features across the dataset, (3) searching for themes by grouping codes into broader patterns, (4) reviewing themes to ensure coherence and relevance, (5) defining and naming themes to capture their essence, and (6) producing the final report that connects the themes to the research questions (Braun & Clarke, 2006).\n\nQuantification was not used in this analysis, as the primary focus was on the depth and richness of qualitative insights rather than numerical representation (Creswell, 2013). Instead, the themes were developed inductively, emerging from the data rather than being pre-determined. Key themes that emerged included university autonomy, administrative challenges, academic freedom, and budgetary constraints.\n\nIn terms of comparative techniques, this refers to the process of systematically comparing data from different sources and categories to identify similarities and differences (Flick, 2018). For this study, comparisons were made between the interviews, observational data, and document analysis. Observations, conducted on academic, administrative, and budget plans using standardized checklists, were cross-referenced with university autonomy guidelines, reports, and other administrative documents. This comparative approach helped to reveal gaps between policy intentions and actual practice (Miles, Huberman, & Saldana, 2014).\n\nObservations were analyzed by matching the data collected using checklists against set criteria from the guidelines and reports, thus providing a structured evaluation of academic and administrative performance (Patton, 2015). Document analysis was performed on university autonomy guidelines, institutional reports, and teaching-learning facilities. The integration of these various data sources helped diversify the data and offered a more comprehensive understanding of the situation under study (Bowen, 2009).\n\n\n4. Result and Discussion\n\nBased on the data gathered from study participants, it was emphasized that institutional autonomy stands out as a fundamental aspect of our university’s values. Participants highlighted how this autonomy serves as the foundation upon which the university operates, allowing it to chart its own course and make decisions that align with its unique mission and values. Institutional autonomy empowers our university to maintain control over academic and administrative affairs, fostering an environment where creativity, innovation, and academic freedom thrive.\n\nParticipants emphasized that this autonomy enables the university to respond dynamically to the evolving needs of students, faculty, and the broader community, ultimately contributing to the institution’s success and reputation. They noted that safeguarding and promoting institutional autonomy will remain a priority to ensure the continued excellence and relevance of our university in the academic landscape (Interview, Hawassa, Addis Ababa, Arbaminch, 2023).\n\nAdditionally, Maassen et al. (2017), highlighted that the autonomy to determine the internal organization of the university, to decide its internal financial affairs, its management, salaries, recruitment of staff and its actions on admissions and its academic content, including its programs, language of instruction and quality assurance, are all crucial elements of institutional autonomy (Maassen et al., 2017). Universities have an obligation to society to safeguard and promote independent institutional decision-making, planning and management, and to rise with their governance bodies the importance and value of institutional autonomy as the necessary pre-condition for the conduct of scholarship and higher education (Maassen et al., 2017).\n\nWe firmly believe that academic excellence thrives in an environment where institutions are granted the autonomy to govern themselves, allowing for innovative approaches to teaching, research, and administration. Our university perceives institutional autonomy not only as a privilege but as a responsibility to uphold the highest standards of integrity, academic freedom, and accountability. Regarding administrative autonomy, we believe that our university leadership should have the flexibility to make decisions pertaining to internal governance structures, personnel management, and strategic planning. This autonomy enables us to respond swiftly to the evolving needs of our academic community and adapt our administrative processes accordingly (KII, Hawassa, 2024).\n\nComing to the challenges, institutional autonomy in Ethiopian universities presents potential challenges when it comes to implementing key governance and structural reforms. Historically, Ethiopian universities have been highly dependent on the government for decision-making in areas like leadership appointments, academic structures, and partnerships with external stakeholders. This dependency has led to a limited capacity for self-governance and flexibility in responding to academic and societal needs (Salmi & Saroyan, 2007). As universities begin to navigate the transition toward greater autonomy, they encounter several challenges related to leadership selection, stakeholder inclusion, and the establishment of partnerships.\n\nOne of the critical issues is the university’s mandate to elect its president, prepare criteria for selection, and potentially dismiss presidents when necessary. While this shift could empower universities to select leaders aligned with their vision, the lack of experience in autonomous decision-making raises concerns about transparency and accountability (Castelló-Climent & Hidalgo-Cabrillana, 2012). According to findings from semi-structured interviews with university administrators, one participant emphasized, “The challenge lies in ensuring that the selection process remains free from political influence, given the long-standing culture of state intervention in university affairs.” Such perspectives echo the broader scholarly concern that newly autonomous institutions may struggle with establishing robust governance practices (World Bank, 2012).\n\nMoreover, the inclusion of civil society and private sector representatives on university boards is intended to broaden perspectives and improve responsiveness to community needs. However, focus group discussions (FGDs) conducted with faculty members revealed apprehensions about potential conflicts of interest and the influence of external actors over academic decisions. One faculty member noted, “Bringing in private sector representatives might shift the focus from academic values to profit-driven motives, risking the university’s commitment to research and education.” Similar findings have been reported by Brezis (2019), who argued that integrating external stakeholders into university governance could undermine academic independence if not carefully managed.\n\nDeciding the academic structure of the university also presents challenges. Traditionally, academic structures in Ethiopian universities have been dictated by national policies, which has led to standardized curriculums and limited flexibility. As universities gain the power to determine their academic programs, they must navigate the challenge of balancing innovation with quality standards. Veugelers (2009) highlighted that rapid shifts in academic structures without adequate preparation can lead to inconsistency in educational quality, which could diminish the credibility of institutions. Interviews with university officials underscored this concern, with one respondent mentioning, “We need to ensure that our newly designed programs meet international standards while also addressing local needs—it’s a difficult balance to strike.”\n\nThe establishment of profit and non-profit entities, both locally and internationally, introduces another layer of complexity. While such initiatives could potentially enhance financial sustainability and innovation within universities, they also come with risks of misaligned priorities. Salmi and Saroyan (2007) found that universities with new profit-oriented ventures often faced tensions between maintaining academic integrity and pursuing financial gains. Document analysis of past university initiatives in Ethiopia indicates that previous attempts to establish income-generating projects were often poorly managed, leading to financial losses and reputational risks.\n\nOverall, the shift toward institutional autonomy for Ethiopian universities is fraught with challenges that require careful navigation. Without the development of strong internal governance frameworks, transparency mechanisms, and capacity-building measures, the risk of missteps in leadership selection, stakeholder engagement, and financial management remains high. As the World Bank (2012) noted, successful institutional autonomy requires a balanced approach, where universities gain freedom but also develop internal checks and balances to ensure their long-term stability and growth. Addressing these challenges is crucial for Ethiopian universities to transition effectively into autonomous entities that can contribute meaningfully to national development.\n\nThe quest for autonomy within Ethiopian universities has been a long-standing issue, tracing back to the establishment of Addis Ababa University in 1950. Historically, these institutions have operated under a centralized governance structure that has consistently limited their independence (University World News, 2023). Despite various legal frameworks advocating for autonomy—such as the 2019 Higher Education Proclamation—the implementation of these policies has often been inconsistent due to ongoing governmental interference (Capital Ethiopia, 2024). This interference manifests in various forms, including stringent oversight over administrative decisions and curriculum development, which undermines the intended autonomy of universities (Kifle, 2022).\n\nAs noted by the Ethiopian Ministry of Education, while universities are granted some level of self-governance, they remain subject to government regulations that restrict their operational freedoms (Capital Ethiopia, 2024). The gap between policy and practice reveals significant challenges; for instance, many universities lack the authority to determine student admissions or develop curricula tailored to local needs (University World News, 2023). Consequently, while formal recognition of autonomy exists, the practical realities hinder universities’ ability to operate independently and effectively respond to academic and societal demands.\n\nThe observation results show that, according to university meeting minutes, most decisions still required approval from higher governmental authorities. This centralization was particularly evident in budget allocations and hiring processes, further reinforcing the lack of administrative autonomy (Observation, 2023).\n\nSupplementing the above, Interview results confirmed that:\n\nThe political landscape in Ethiopia significantly influences how universities are governed. Appointments are often based on political affiliations rather than expertise, which leads to a lack of diversity in thought and action. This dynamic creates an environment where academic freedom is not fully realized, impacting the quality of education and research output. During my tenure, I experienced firsthand the challenges of navigating government policies while trying to maintain institutional integrity. While I acknowledge the need for some level of oversight, the excessive control inhibits our ability to manage effectively. True autonomy means being able to make decisions that align with our mission without fear of government repercussions. Until this balance is achieved, our higher education system will struggle to thrive (Interview, Hawassa, 2023).\n\nThe quest for autonomy within Ethiopian universities has been a long-standing issue, tracing back to the establishment of Addis Ababa University in 1950. Historically, universities in Ethiopia have operated under a centralized governance structure, which has consistently limited their independence. Despite the enactment of various legal frameworks advocating for autonomy, such as the 2019 Higher Education Proclamation, implementation has often been inconsistent due to governmental interference. As noted by Abebaw (2021), “Any gap between regulatory promises and realization will defeat the purpose of the current exercise and the long-term interests of the sector.” Furthermore, the Ethiopian Ministry of Education’s recent announcements regarding increased oversight have raised concerns about the future independence of these institutions (Capital Ethiopia, 2024).\n\nOn the other hand, focus group discussion participants highlighted that:\n\nThe focus group participants discussed how political interference remains a significant barrier to administrative autonomy. One participant noted, “Even though universities are supposed to be independent, decisions, especially at the leadership level, are often influenced by political actors, which undermines genuine autonomy (FGD, Hawassa, 2023).\n\nAs articulated in a recent report, “Universities have always deplored the limitations they face in terms of exercising their full power and the unlawful interference from the government which disrupts their normal functions” (KII, Arbaminch, 2023). Furthermore, an interview with a university faculty member revealed, “We have seen many proclamations aimed at granting autonomy, yet in practice, the government’s oversight is pervasive” (Interview, 2024). This sentiment is echoed in the findings of Abebaw (2021), who emphasizes that governmental interference fundamentally undermines institutional independence.\n\nConsistent with the above assertions, interview results attested that:\n\nDespite the existence of policies that promote autonomy, our day-to-day operations are still heavily influenced by the government. The constant oversight creates a culture of compliance rather than innovation. Many of us feel constrained in our ability to pursue academic freedom, as our initiatives often require approval from the Ministry of Education (Interview, University Faculty Member, 2024)\n\nRecent developments indicate a tightening grip on university autonomy by the Ethiopian government. In June 2024, the Ministry of Education announced increased oversight over autonomous universities. The Education Minister asserted, “The fact that autonomous universities have their own guidelines does not mean that they operate without law,” indicating a persistent emphasis on governmental oversight despite promises of independence (Capital Ethiopia, 2024).\n\nThis shift towards tighter government control raises significant concerns among education experts regarding the future independence and competitiveness of Ethiopia’s higher education system. A higher education analyst noted, “The government’s decision to tighten control is alarming, as it goes against global trends where institutions are granted more independence to foster innovation and responsiveness” (Interview, Addis Ababa 2024). This regression undermines the foundational principles of higher education, where academic institutions are typically expected to operate with a degree of autonomy that fosters critical thinking and innovation.\n\nOn the other hand, political ideology significantly shapes university governance in Ethiopia. The appointment of key administrative positions is often influenced more by political affiliations than by meritocratic criteria. A higher education policy expert commented, “The political landscape heavily influences the appointments of faculty and administrative leaders, resulting in a lack of diversity and stifling innovation” (KII, Arbaminch, 2023). This dynamic not only threatens academic freedom but also compromises the integrity of academic institutions.\n\nExpert from the Ministry of Education emphasized that an authorized university must possess both academic freedom and organizational autonomy: “An authorized university has a higher responsibility beyond conventional duties … having authority beyond academic freedom” (Interview, Addis Ababa, 2022). However, despite these proclamations, many institutions still face substantial state interference that limits their operational freedoms. A university administrator remarked, “While we are expected to be independent, the reality is that our governance is heavily dictated by the government” (Interview, Arbaminch, 2024).\n\nMoreover, resistance to change is another critical barrier to achieving administrative autonomy. Many stakeholders within universities are accustomed to existing governance structures and may fear instability or job losses associated with reforms. An interviewee expressed, “There’s a sense of comfort in the status quo; people are afraid that changes could lead to their job losses” (Interview, Hawassa, 2024). This reluctance is compounded by bureaucratic inertia and complex administrative frameworks that hinder effective governance initiatives.\n\nSupplementing the above assertions, Key informant noted that:\n\nWhile self-governance is not a new concept—citing previous periods of autonomy—current leadership faces significant challenges. The university authorization will have a big challenge, especially regarding university leadership. In light of these challenges, a stakeholder commented, There is a palpable fear among faculty about potential reprisals from the government if they advocate too strongly for autonomy (KII, Hawassa, 2024).\n\nThe situation in Ethiopia reflects broader global trends regarding university autonomy. Many countries have recognized the importance of granting greater independence to higher education institutions as a means to foster innovation and responsiveness to societal needs. However, Ethiopia’s unique historical and political landscape presents distinct challenges.\n\nGlobal examples, such as the experiences of institutions like Oxford and Harvard, illustrate how institutional autonomy can lead to improved academic performance and resilience. These institutions benefit from diverse funding streams and robust governance mechanisms that allow for greater flexibility and efficiency. A comparative analysis reveals that Ethiopian universities could benefit significantly from adopting best practices in governance and funding, which would enable them to become more competitive on the global stage.\n\nThus, the potential challenges to administrative autonomy in Ethiopian public universities reflect a complex landscape shaped by historical legacies, political dynamics, and ongoing government control. Insights drawn from interviews reveal that achieving genuine autonomy requires addressing these multifaceted challenges through structural reforms and effective policy implementation.\n\nWhile recent proclamations suggest a movement towards greater independence for universities, the reality remains fraught with obstacles that undermine both academic freedom and institutional effectiveness. A university faculty member poignantly stated, “We need a shift in mindset, both from the government and the institutions, to create a culture that values true academic independence” (KII, Hawassa, 2024). Addressing these issues will necessitate a concerted effort from all stakeholders involved—government officials, university administrators, faculty members—to cultivate an environment conducive to genuine academic independence and responsiveness to societal needs.\n\nConsistent with the above findings, Principal-Agent Theory (PAT) and administrative autonomy justify and support the analysis of the challenges Ethiopian public universities face in gaining independence from centralized control. PAT examines the relationship between the principal (the government) and the agent (the universities), wherein the principal delegates authority but retains significant oversight. This theory helps explain why the Ethiopian government, as the principal, is reluctant to fully transfer decision-making powers to universities due to concerns about accountability, political stability, and maintaining national standards.\n\nIn the context of administrative autonomy, PAT highlights how universities are constrained by government regulations and political interference, limiting their ability to self-govern. The theory suggests that the government’s tight control over key administrative functions—such as hiring, governance structures, and operational policies—prevents universities from fully exercising autonomy. While universities act as agents tasked with managing their internal affairs, their ability to do so independently is restricted by the government’s need to ensure that their operations align with national priorities (Shattock, 2019). PAT thus provides a critical framework for understanding the root of these administrative autonomy challenges, demonstrating how the tension between government oversight and university independence continues to impede the full realization of administrative self-governance in Ethiopian public universities.\n\nAdministrative autonomy is vital for universities to maintain a competitive academic environment by attracting and retaining qualified staff. This autonomy allows for flexibility in recruitment, remuneration, and career development, which are key to building a vibrant academic community.\n\n• Recruitment and Hiring of Academic and Administrative Staff: Autonomy in hiring enables universities to select candidates who align with their strategic needs and academic culture. An FGD participant highlighted, “Having control over recruitment means we can prioritize hiring faculty who bring innovative research and teaching methods.” This flexibility is crucial for fostering a dynamic academic environment that supports student learning and research excellence. Research by Marginson (2016) has shown that universities with hiring autonomy are better able to adapt to emerging academic fields and attract top talent. However, interviewees pointed out that without clear guidelines, recruitment processes could be subject to favoritism and biases.\n\n• Determining Salaries: Setting competitive salaries for both academic and administrative staff is essential for attracting and retaining talent. An administrator in a semi-structured interview explained, “Salary autonomy allows us to reward high-performing faculty members and address disparities that may arise due to market dynamics.” The ability to adjust salaries can help universities remain competitive in attracting skilled staff, particularly in fields with high demand (Veugelers, 2009). However, the challenge lies in ensuring fairness and consistency, as disparities in pay scales can lead to dissatisfaction and conflict among staff.\n\n• Deciding on Termination: The ability to terminate staff based on legal procedures allows universities to maintain high standards of performance and accountability. An FGD participant stated, “The power to decide on termination enables us to address issues of underperformance directly, which is essential for maintaining academic integrity.” This autonomy is vital for upholding a culture of excellence, as it allows institutions to act promptly on matters affecting the quality of education. However, as noted by Salmi (2009), termination processes must be transparent and based on clear criteria to avoid legal challenges and ensure fairness.\n\n• Managing Career Promotions: Autonomy over promotion policies enables universities to recognize and reward academic achievements. Interviewees emphasized that “Autonomy in promotions allows us to create career paths that encourage continuous professional development among our faculty.” This flexibility is critical for motivating staff and fostering a culture of excellence in teaching and research. Studies support this, showing that institutions with independent promotion policies often see higher levels of staff satisfaction and productivity (Altbach & Salmi, 2011). Nevertheless, interview insights suggest that ensuring objectivity and avoiding biases in promotions is a major challenge, necessitating clear and transparent guidelines.\n\nMajor Challenges:\n\n○ Inconsistent Recruitment Practices: Interviews with human resources managers highlighted issues in establishing recruitment policies that balance transparency with autonomy. A university HR director noted, \"We are still developing criteria for recruitment, and there is confusion about the extent to which we can modify existing procedures.\" Ashcroft and Rayner (2021) similarly observed that inconsistent recruitment practices can emerge in institutions with newly granted autonomy, resulting in disparities in faculty quality.\n\n○ Determining Competitive Salaries: FGDs with faculty members underscored the challenges in setting competitive salaries. One participant mentioned, \"With our limited resources, it is hard to match the salaries offered by private institutions or international universities, leading to a brain drain.\" This issue is consistent with Alemayehu and Yizengaw’s (2020) study, which highlighted the struggles faced by Ethiopian universities in retaining talent due to inadequate salary structures and benchmarking practices.\n\n○ Challenges in Career Development: Interviews with academic staff indicated dissatisfaction with promotion criteria, citing a lack of transparency and clear metrics. An assistant professor noted, \"We need a fair and transparent system for promotions; otherwise, it leads to frustration among staff.\" This sentiment echoes the International Institute for Educational Planning (IIEP) (2019), which found that many African universities lack robust frameworks for career progression, resulting in perceptions of favoritism and inequity.\n\nAcademic freedom, often referred to as academic autonomy, is a fundamental principle that underpins the operations of higher education institutions. It asserts that academic personnel—faculty and researchers—should have the freedom to make independent decisions regarding their core activities, particularly in teaching and research. This autonomy is crucial for fostering an environment where scholars can pursue knowledge without undue influence or restrictions from external entities, including governmental bodies, administrative structures, or commercial interests (Nussbaum, 2021).\n\nIn similar vein, focus group discussion participants highlighted the struggle between granting universities autonomy and ensuring accountability is one of the challenges. While many agreed that autonomy could enhance decision-making and responsiveness, concerns were raised about the potential lack of oversight. One participant stated, “Autonomy should not mean independence from accountability; rather, it should be about institutions managing their affairs while adhering to national standards (FGD, Arbamich, 2023. Moreover, FGD discussion results, the major challenge will be the tension between standardized curricula and academic freedom. Several participants pointed out that universities are constrained by rigid national accreditation requirements, which limit their ability to innovate academically. “We want to design programs that respond to local needs, but the centralized accreditation system makes it difficult,” remarked one academic leader (FGD, Addis Ababa, 2023).\n\nIn the realm of teaching, academic freedom allows educators to explore diverse pedagogical approaches, develop curricula, and select materials that align with their scholarly expertise and values. This flexibility encourages innovation in the classroom and promotes a richer educational experience for students, who benefit from exposure to various perspectives and methodologies (Krause et al., 2020; Trowler, 2022). Similarly, observations in academic departments revealed limited flexibility in curriculum design. Faculty members expressed frustration over the rigid approval processes for new courses and programs, which stifled creativity and adaptability to emerging academic fields and local contexts (Observation, 2023).\n\nSimilarly, in research, academic freedom empowers scholars to investigate and address topics of their choosing, contributing to the advancement of knowledge in their fields. It supports the exploration of controversial or unorthodox ideas, which can lead to significant breakthroughs and societal progress. By safeguarding researchers from censorship or retaliation for their findings, academic freedom enhances the integrity and credibility of the academic community (Bennett et al., 2020; Association of American Colleges & Universities [AAC&U], 2022).\n\nThe discussion on academic autonomy, particularly in the context of Ethiopian universities, highlights significant challenges and considerations that must be addressed to safeguard the independence of these institutions. Based on the data gathered from key informants, it is evident that academic autonomy is crucial for universities to exercise control over their curricula, academic standards, and research agendas (KII, Arbaminch, 2023). However, the ongoing autonomization process presents a series of hurdles that could potentially undermine the essence of academic autonomy.\n\nA central challenge identified is the tension between standardization and diversity in academic offerings. As Ethiopian universities move toward automation and seek to streamline processes, there is a risk that standardization could overshadow the unique academic approaches and curricula that institutions need to tailor to their specific contexts (KII, Hawassa, 2023). This concern echoes findings from previous studies, which also stress the potential suppression of academic diversity in favor of efficiency (Aboye, 2021; Getu, 2021). In their efforts to meet national and institutional benchmarks, universities may find their academic autonomy constrained, preventing them from addressing the diverse educational needs of their students and the community at large (Teferra, 2018).\n\nAnother critical issue is the implementation of the new higher education proclamation, which emphasizes various aspects of governance, academic affairs, and accountability. While the proclamation sets clear standards for financial audits and administrative responsibilities, it leaves key aspects of academic autonomy under-examined, particularly in terms of quality assurance and curriculum diversity. The two-year timeline set for the implementation of these reforms further compounds concerns, as it raises questions about whether institutions will have the time and resources to fully adapt without compromising their autonomy (Aboye, 2021).\n\nThe study participants pointed to quality assurance as another significant challenge. While academic autonomy allows universities to establish their own standards, the lack of centralized oversight could lead to inconsistencies in the quality of education across different institutions. This variability may pose challenges in terms of accreditation and the recognition of degrees both nationally and internationally (Interview, Hawassa, 2024). This issue is especially pertinent in Ethiopia’s higher education system, where the rapid expansion of universities has placed immense pressure on traditional governance and oversight models.\n\nTechnological dependency further complicates the autonomy debate. As universities integrate automation technologies into their academic and administrative processes, they may become overly reliant on specific platforms and tools. This dependency could limit their flexibility in curriculum design and research methodologies, ultimately restricting their ability to innovate and pursue diverse academic goals. Informants highlighted that such technological constraints could diminish the freedom that academic autonomy is meant to provide (Interview, Arbaminch, 2024).\n\nThe relevance and responsiveness of academic programs also emerged as key considerations. With Ethiopia’s diverse socio-political landscape, maintaining academic programs that reflect the country’s needs while preserving student diversity is a complex task. This challenge is compounded by the government’s growing difficulty in regulating the expanding number of higher education institutions. Universities are thus faced with the dual responsibility of fostering academic freedom while ensuring that their programs remain relevant and inclusive (Interview, Addis Ababa, 2023).\n\nThe expansion of higher education in Ethiopia has brought both opportunities and risks. On one hand, greater institutional autonomy holds the potential to improve the quality of education, research, and community engagement. On the other hand, the challenges outlined—standardization pressures, quality assurance gaps, technological dependence, and governance constraints—pose serious threats to the effective realization of academic autonomy. Addressing these issues requires universities to adopt adaptable governance structures, encourage stakeholder engagement, and foster ongoing dialogue to ensure that autonomy strengthens, rather than weakens, the quality of education.\n\nThus, while academic autonomy in Ethiopian universities is seen as a vehicle for innovation, excellence, and institutional resilience, its full potential remains hindered by various challenges. A careful balance between automation and autonomy, diversity and standardization, and flexibility and accountability is essential to empower universities to thrive in a rapidly changing academic environment. Only through robust governance mechanisms and collaborative decision-making processes can academic autonomy be truly realized and sustained.\n\nPrevious research emphasizes the fundamental role of academic autonomy in fostering institutional innovation and quality education. For instance, Belgaroui and Hamad (2021) argue that autonomy allows universities to make strategic decisions independently, which is crucial for their ability to develop contextually relevant curricula, research agendas, and academic standards. However, studies also show that academic autonomy often comes into tension with governmental control, especially in countries where education is seen as a critical tool for national development. This tension reflects similar concerns identified in this study, where the Ethiopian government’s new higher education proclamation raises fears of excessive standardization and the suppression of diversity in academic offerings (Aboye, 2021).\n\nIn line with these findings, Teferra (2018) argue that while efforts to improve efficiency through standardization are necessary, they often come at the cost of institutional autonomy. Their research shows that universities in Ethiopia and other African countries frequently struggle to maintain the balance between adhering to national standards and preserving their unique academic identities. The concern that automation could drive uniformity in academic programs, thereby limiting universities’ ability to address local needs, is a recurring theme in both past studies and the current findings.\n\nThe issue of quality assurance, another significant challenge raised in this study, has also been highlighted in earlier research. Aboye (2021) and Getu (2021) stress the difficulties associated with ensuring consistent educational quality across decentralized and autonomous institutions. Without adequate oversight mechanisms, the risk of disparities in academic rigor and the quality of instruction increases, potentially undermining the credibility of degrees awarded by autonomous universities. This aligns with the concerns expressed by key informants in this study, who emphasized that the lack of centralized quality assurance could lead to accreditation and recognition issues both nationally and internationally (KII, Hawassa, 2024).\n\nMoreover, past studies highlight the risks associated with the technological dependency of universities. As automation becomes more prevalent, the flexibility and innovation in academic programs may be constrained by the limitations of the technology used. Similar to the current findings, previous studies have pointed out that over-reliance on specific automation platforms can reduce universities’ ability to pursue diverse research agendas and curricula that do not align with the capabilities of the tools at hand (Teferra, 2018). This challenge is especially pertinent in Ethiopia, where technological infrastructure is still developing, and universities may struggle to keep up with the demands of modern automation tools.\n\nIn terms of governance, the rapid expansion of Ethiopia’s higher education sector has put immense pressure on traditional governance models, as highlighted in both this study and earlier works. According to Teferra (2018), the proliferation of universities in Ethiopia has made it increasingly difficult for the government to effectively regulate the sector, leading to governance challenges that undermine institutional autonomy. This study echoes those findings, with key informants pointing out that the rapid growth of higher education institutions has led to governance strain and has highlighted the need for more adaptable and flexible governance frameworks (Interview, Arbaminch, 2024).\n\nConsistent with the above findings, Institutional Theory best fits the analysis of challenges to academic autonomy in Ethiopian public universities. This theory explains how universities are shaped by external pressures, formal structures, and cultural norms, which can either support or constrain their academic independence. In the context of Ethiopian universities, academic autonomy refers to the ability to independently determine curricula, research agendas, and quality assurance processes without external interference.\n\nInstitutional Theory highlights how academic autonomy is often limited by government-imposed standards, accreditation bodies, and international benchmarks. These institutions impose rigid frameworks that universities must follow to maintain credibility and compliance. As a result, Ethiopian universities face challenges in innovating or tailoring academic programs to their specific contexts, as they are required to conform to national education policies and quality standards. The theory also points out how deeply embedded cultural and bureaucratic norms can hinder efforts to break away from these centralized academic controls (DiMaggio & Powell, 1983).\n\nThus, Institutional Theory helps explain why Ethiopian universities struggle to achieve full academic autonomy, as they are constrained by both formal governmental structures and the institutionalized norms of higher education governance. It underscores the tension between the desire for academic freedom and the need to meet external expectations, highlighting how these external pressures shape the academic decisions universities make.\n\nAcademic autonomy is fundamental for universities to develop and manage their educational programs, ensuring that they can innovate and adapt to societal needs. This autonomy allows institutions to control admissions, program design, and quality assurance measures, thus shaping their academic identity.\n\n• Deciding on the Number of Newly Admitted Students: Controlling student intake enables universities to maintain optimal class sizes and ensure that resources match the number of enrolled students. According to an interviewee, “We can better manage our teaching loads and student services when we decide on the number of admissions.” Studies have shown that such control is vital for maintaining academic standards and ensuring quality education (Brezis, 2019). However, without adequate planning, there is a risk of either under-enrollment, leading to resource underutilization, or over-enrollment, which can strain facilities.\n\n• Initiating or Terminating Education Programs: The ability to independently launch or discontinue programs enables universities to respond swiftly to changing market demands and student interests. An FGD participant noted, “Program autonomy allows us to innovate in our curriculum and offer courses that are relevant to the current job market.” This adaptability is crucial for maintaining relevance in an evolving academic landscape (Castelló-Climent & Hidalgo-Cabrillana, 2012). However, participants cautioned that frequent changes to programs could disrupt students’ academic progression, highlighting the need for stability alongside innovation.\n\n• Quality Assurance: The freedom to choose quality assurance techniques allows universities to adopt standards that reflect their unique educational philosophy. Interview feedback suggested that “Autonomy in quality assurance helps us maintain high standards tailored to our mission.” This aligns with research by Altbach (2013), which emphasizes that institutions with independent quality assurance mechanisms are better able to maintain academic integrity and improve student outcomes. Nonetheless, the absence of external checks could lead to variability in standards, making external accreditation frameworks a necessary complement.\n\nMajor Challenges:\n\n○ Balancing Student Admission and Quality: FGDs with university admission officers highlighted challenges in balancing increasing student intake with maintaining academic quality. One admission officer stated, \"We are under pressure to admit more students, but without the necessary resources, it’s hard to maintain quality standards.\" This reflects findings by Altbach and de Wit (2020), who note that universities in developing countries, including Ethiopia, often face a conflict between expanding access to higher education and preserving academic standards.\n\n○ Developing Independent Quality Assurance Mechanisms: Interviews with university administrators emphasized the difficulty of establishing internal quality assurance mechanisms. A quality assurance officer remarked, \"We are used to external evaluations, and building our capacity for self-assessment is challenging.\" This is consistent with Hayward (2018), who found that building internal quality assurance capabilities is crucial for maintaining academic standards but requires substantial investment in capacity-building initiatives.\n\n○ Limited Experience in Program Innovation: FGDs with deans and department heads revealed that while universities have the autonomy to initiate new programs, many lack the research capacity to identify market demands. One dean mentioned, \"We need data on job market trends to align our programs with the economy’s needs, but that capacity is currently lacking.\" This aligns with Alemayehu and Yizengaw (2020), who highlighted that the absence of market research capacity in Ethiopian universities limits their ability to innovate and adapt academic offerings to evolving labor market needs.\n\nFinancial autonomy for universities refers to their capacity to generate and manage independent revenue streams, allowing them to ensure sustainability without over-reliance on government funding. Key informants underscored the importance of financial autonomy for the sustainability and growth of universities, stating that it enables efficient resource allocation, investments in infrastructure and technology, and the pursuit of strategic partnerships that enhance academic programs and research initiatives. One informant articulated, “By managing our finances independently, we can ensure fiscal responsibility while pursuing our mission of providing accessible and high-quality education to our students” (KII, Arbaminch, 2023). This perspective aligns with the literature emphasizing that financial independence is critical for enhancing institutional effectiveness and adaptability.\n\nFGD participants expressed concern over the lack of financial autonomy, particularly the limited avenues for generating independent revenue. “Universities are overly dependent on government funding,” one participant explained. “This dependency makes it hard to explore alternative revenue streams and build sustainable financial models” (FGD, Hawassa, 2023).\n\nCampus observations showed that universities had minimal engagement in revenue-generating activities beyond tuition fees. University enterprises, such as research consultancies and service provision units, were either underdeveloped or lacking entirely, indicating weak financial autonomy. In addition, observations of campus facilities highlighted infrastructural challenges, particularly in the maintenance of teaching and research facilities. Poor resource management was a recurring theme, with several buildings and equipment in need of repair, further limiting the capacity for universities to function autonomously (Observation, 2023).\n\nThe financial sustainability of Ethiopian universities, particularly Addis Ababa University, Hawassa University, and Arbaminch University, relies heavily on the budget allocated from the government. They have week and insignificant internal revenue generation experiences and strategies. Thought it is insignificant, these institutions employ various approaches to generate income, which insignificantly contributes to their operational budgets. Recent estimates indicate that Addis Ababa University generates approximately 50 million Ethiopian Birr (ETB) from internally generated revenues, while Hawassa University and Arbaminch University produce around 25 million ETB and 10 million ETB, respectively (Ethiopian Ministry of Education, 2023). The various strategies and sources for generating internal income are discussed below.\n\n4.4.1 Distance Education Programs\n\nA major revenue source for these universities is distance education programs, particularly in the social sciences. For example, Addis Ababa University reported that distance education accounts for approximately 35% of its total internal revenue (Addis Ababa University Financial Overview, 2023). The cost structure for distance education varies, with self-sponsored students paying between 40 to 55 ETB per credit hour, while government-sponsored students pay 50 ETB (World Bank, 2020). However, the nature of these programs limits the inclusion of practical-oriented courses, which may affect student enrollment and revenue potential.\n\nKey informant interviews with university administrators revealed that while distance education provides a significant revenue stream, the universities face challenges in maintaining the quality and relevance of these programs. One administrator stated, “We need to innovate our curriculum and delivery methods to attract more students and improve our revenue from distance education” (KII, Hawassa University, 2023).\n\n4.4.2 Short-Term Training for Organizations and Consultancy Services\n\nShort-term training programs also contribute to revenue generation, albeit to a lesser extent. These programs typically focus on skills such as computer literacy and management. At Addis Ababa University, they account for about 5% of total revenue (Hawassa University Annual Report, 2023). However, there is significant potential for growth in this area. Administrators noted the need for enhanced marketing and diversification of training topics to attract more participants. Interviews with training coordinators highlighted the importance of aligning training offerings with market demand. A coordinator mentioned, “If we expand our training programs to include in-demand skills, we could significantly increase our revenue from this source” (KII, Arbaminch University, 2023).\n\nConsultancy services are another underutilized revenue stream for these universities. Despite having qualified experts, revenue from consultancy services constitutes less than 5% of their internal revenue (Ethiopian Ministry of Education, 2023). The lack of institutional support and promotion for consultancy services limits their effectiveness. For instance, while Arbaminch University has established a consultancy bureau, Addis Ababa and Hawassa Universities have not yet institutionalized similar frameworks.\n\nA key informant from Addis Ababa University commented, “There is a wealth of expertise within our faculty that could be monetized through consultancy, but we lack the organizational structure to make it happen” (KII, Addis Ababa University, 2023). This suggests a need for improved institutional frameworks to facilitate and promote consultancy services.\n\n4.4.3. Revenue from Physical Facilities and from Registrar Office Services\n\nRevenue from physical facilities, including workshops and agricultural lands, varies among the universities. Hawassa University’s furniture workshop, for instance, contributes approximately 20% of its total internal revenue (Hawassa University Annual Report, 2023). Furthermore, while all universities possess agricultural lands that can be utilized for revenue generation, Hawassa University excels in mechanized farming, contributing about 18% of its internally generated funds. Rental income from university facilities also serves as a revenue source. Addis Ababa University, for example, generates around 7% of its internal revenue from leasing spaces for conferences and events. In contrast, Arbaminch University could enhance its revenue generation by expanding its leasing strategies and promoting its facilities to external stakeholders.\n\nRegistrar office services, which include documentation fees, transcripts, and application fees, generate varying levels of revenue across the universities. In Arbaminch University, these services account for approximately 0.02% of total revenue, whereas they contribute about 6% at Addis Ababa University (Addis Ababa University Financial Overview, 2023). By enforcing fee structures consistently across all universities, these institutions could transform registrar services into a more reliable revenue source.\n\nThe internally generated revenue contributes insignificantly to the operational budgets of the selected universities. Addis Ababa University’s internal revenue accounts for approximately 13% of its recurrent budget, while Hawassa University and Arbaminch University contribute around 5% and 3%, respectively (Ethiopian Ministry of Education, 2023). This financial contribution highlights the pressing need for these universities to enhance their income-generating strategies to attain greater financial autonomy.\n\nAccording to the World Bank’s Task Force on Higher Education and Society (2000), successful revenue diversification in universities requires a conducive legal framework, institutional capacity, and market responsiveness. In Ethiopia, universities are allowed to own property and engage in consultancy services; however, effective implementation of these opportunities remains a challenge.\n\nThe Ethiopian government has decentralized various responsibilities to public universities, enabling them to explore alternative funding sources. Despite this progress, significant barriers persist in realizing the full potential of financial autonomy. Interviews with university leaders emphasize the need for institutional support and strategic planning to capitalize on existing opportunities. One university leader stated, “Achieving financial autonomy is a long-term goal, but we must take concrete steps now to diversify our revenue streams” (KII, Hawassa University, 2023).\n\nStudy participants highlighted that:\n\nWhile Addis Ababa University, Hawassa University, and Arbaminch University have adopted various strategies for revenue generation, the heavy reliance on distance education and summer programs indicates an underutilization of alternative sources. To ensure the sustainability of self-sponsored programs, continuous market analysis and curriculum adjustments are essential. Currently, many distance education programs have been discontinued due to the new education reform in the country. This shift has significantly impacted universities’ income streams, as distance education was a key source of revenue for these institutions. Greater institutional focus on consultancy services, expansion of training programs, and improved revenue generation from physical facilities will significantly enhance income levels (Interview, Experts from Minster of Education, 2023).\n\nDespite efforts to generate internal revenue, these universities have struggled to produce sufficient income to alleviate their dependency on government support. One of the key challenges in enhancing financial autonomy is the insufficient diversification of revenue generation strategies. Although these universities employ various methods—such as distance education, short-term training programs, and consultancy services—these initiatives have not yielded adequate income to substantially reduce reliance on government support (KII, Expert from Minister of Education, 2024). For example, while distance education contributes significantly to revenue at Addis Ababa University, it remains inadequate for addressing the institution’s comprehensive financial requirements (Jemal, 2023). Moreover, consultancy services, despite their potential for income generation, have been largely underutilized across these institutions, with revenues contributing less than 5% of internal income (Federal Ministry of Education, 2023).\n\nOther studies indicate a critical need for strategic planning and implementation to improve revenue generation capabilities. Universities should consider exploring innovative approaches that expand training programs, increase the scope of consultancy services, and enhance marketing strategies for distance education. Additionally, fostering partnerships with industry stakeholders and leveraging faculty expertise can create further funding opportunities (World Bank, 2020).\n\nFurthermore, the financial constraints experienced by these universities have notable implications for the quality of education and student access. Limited internal funding can hinder the development of essential infrastructure, faculty recruitment, and the availability of learning resources. Such financial limitations may ultimately compromise the educational experience for students, reducing the overall effectiveness of higher education institutions in Ethiopia (Tadesse, 2022).\n\nHowever, the pursuit of financial sustainability presents several challenges. A primary obstacle is the limited revenue sources available to universities, which often leads to overdependence on tuition fees and government grants. This reliance can render institutions vulnerable to fluctuations in enrollment numbers and changes in government funding policies (KII, Hawassa, 2023). As previous studies have indicated, the challenges of transitioning to financial autonomy from government dependency are multifaceted. Getu (2021), Feleke (2014), and Gebru et al. (2020) identify the perceived low financial autonomy of Ethiopian public universities as a significant hurdle. Despite promises of increased independence, these institutions continue to experience substantial government control, which restricts their capacity to manage resources effectively and make timely, context-specific decisions.\n\nMoreover, financial challenges are exacerbated by high administrative and non-instructional costs, poor management practices, and a lack of transparent procurement processes. Feleke (2014) argues that these issues not only contribute to financial inadequacy but also negatively impact the core missions of universities, such as teaching, learning, and research activities. Additionally, Aboye (2021) highlights that the shift toward greater autonomy within the public sector, aimed at reducing reliance on public funds, introduces further complexities. Universities often struggle to exercise their financial autonomy effectively due to managerial inexperience, fear of decision-making, and reluctance to assume necessary financial risks, which collectively hinder effective financial management.\n\nIn addition to these internal challenges, universities face stiff competition for funding from various external sources, including research grants, philanthropic donations, and corporate partnerships. Securing these funds necessitates significant investments in research capabilities and fundraising infrastructure, which can be particularly burdensome for institutions in developing countries. The ongoing operational costs and the necessity for state-of-the-art infrastructure can strain financial resources, potentially impacting investments in faculty development and student support services (Interview, Hawassa, 2023). Furthermore, while increasing tuition fees may appear to be a straightforward solution for revenue generation, this approach must be considered in light of its implications for affordability and accessibility, particularly for students from disadvantaged backgrounds. Achieving a balance between financial sustainability and equitable access to education requires careful consideration and innovative approaches to tuition pricing and financial aid.\n\nConsequently, with financial autonomy comes the responsibility for transparent and accountable financial management. Establishing robust governance structures, financial controls, and oversight mechanisms is crucial to ensuring effective management of revenue in alignment with institutional priorities. Key informants contend that addressing these challenges requires proactive strategic planning, collaboration with stakeholders, and a willingness to innovate in revenue generation and financial management practices. Potential strategies include exploring alternative revenue sources, such as the commercialization of research outcomes, continuing education programs, and partnerships with industry and government agencies. Furthermore, fostering a culture of financial literacy among faculty, staff, and students can contribute to long-term financial sustainability (KII, Hawassa, 2023).\n\nTo facilitate the transition toward financial autonomy, universities should consider several strategic steps. First, developing a comprehensive strategic plan that outlines clear goals, objectives, and milestones for achieving financial autonomy is essential. Engaging stakeholders across the university community in the planning process will build consensus and ownership of the transition strategy. Second, universities must identify and cultivate diverse revenue sources beyond government funding and tuition fees. This can be achieved by exploring opportunities for revenue generation through research commercialization, corporate partnerships, philanthropic donations, and fee-based services (KII, Addis Ababa, 2023).\n\nInvesting in building institutional capacity for revenue generation, financial management, and entrepreneurial activities is crucial. Providing training and support for faculty, staff, and administrators to develop skills in fundraising, budgeting, financial analysis, and risk management will enhance the overall capacity of universities to achieve financial autonomy. Furthermore, forging strategic partnerships with industry, government agencies, non-profit organizations, and international institutions can leverage resources and expertise for mutual benefit.\n\nConsistent with the above findings, Resource Dependency Theory (RDT) best fits the analysis of challenges to financial autonomy in Ethiopian public universities. This theory posits that organizations depend on external resources for survival and that their financial decisions are heavily influenced by these dependencies. In the context of Ethiopian public universities, financial autonomy refers to their ability to independently secure funding and allocate resources without being overly reliant on government support.\n\nRDT highlights how Ethiopian universities face significant challenges in achieving financial autonomy due to their dependence on government funding, which is often insufficient and unpredictable. This reliance constrains their ability to make independent financial decisions and develop diverse revenue streams. As universities depend primarily on state allocations, they are subject to governmental priorities and budgeting processes, which may not align with their institutional goals (Pfeffer & Salancik, 2003). This situation often results in a reactive approach to budgeting, limiting universities’ capacity to invest in innovative programs, infrastructure, or research initiatives.\n\nFurthermore, Resource Dependency Theory underscores the importance of developing alternative funding sources to mitigate financial constraints. However, Ethiopian universities often struggle to attract private investments, secure research grants, or foster partnerships with industry, further limiting their financial autonomy. The inability to diversify funding creates a cycle of dependency that inhibits operational flexibility and hinders long-term planning.\n\nThus, RDT provides a crucial framework for understanding the challenges of financial autonomy in Ethiopian public universities. It illustrates how their reliance on government funding shapes their financial strategies and highlights the need for universities to develop innovative revenue-generating mechanisms to enhance their financial independence and sustainability.\n\nFinancial autonomy is essential for universities seeking to strengthen their ability to manage resources, make independent strategic decisions, and respond effectively to emerging academic and infrastructural needs. Several aspects of financial autonomy, including negotiating project timelines, managing diverse funding sources, and controlling surplus income, are fundamental for enhancing institutional flexibility.\n\n• Negotiating the Time Span of Projects: Universities with financial autonomy can negotiate project timelines with funding bodies, which allows them to synchronize these projects with their strategic goals and internal capabilities. According to an FGD participant, “The freedom to negotiate project timelines helps the university align project milestones with our research agendas, ensuring that we do not rush through critical processes.” This flexibility is crucial for maintaining quality in research and development initiatives. Similar studies have highlighted that institutions with greater financial control tend to have better project management outcomes, as they can align funding schedules with long-term academic goals (Salmi & Saroyan, 2007; Altbach, 2013). However, participants in semi-structured interviews emphasized that the lack of negotiation skills and experience could pose challenges, leading to delays or unmet expectations.\n\n• Choosing Among Different Types of Governed Finances: Financial autonomy also empowers universities to diversify their income sources, choosing between government grants, private sector funding, and research collaborations. An interviewee noted, “Having the autonomy to select our funding model means we are not entirely dependent on fluctuating government budgets.” This diversification is crucial in managing financial risks, particularly during economic downturns when public funding may decline. Studies indicate that universities with the ability to choose their funding models can achieve financial resilience by balancing multiple revenue streams (Castelló-Climent & Hidalgo-Cabrillana, 2012; World Bank, 2012). However, managing multiple funding sources can also increase administrative complexity, requiring strong governance and financial management frameworks to ensure accountability and effective use of funds.\n\n• Utilizing Remaining Income: Autonomy over surplus income allows universities to reinvest in priority areas, such as expanding research facilities, enhancing student services, or offering scholarships. As one FGD participant explained, “When the university has the power to decide on the use of remaining income, we can prioritize strategic initiatives without waiting for external approvals.” This ability to channel surplus funds into institutional priorities aligns with findings from Veugelers (2009), which highlight that financially autonomous universities often perform better in research and innovation. Nevertheless, participants noted the risks of misallocation or favoring short-term projects over long-term sustainability if financial governance structures are weak.\n\n• Borrowing from Financial Institutions: The ability to secure loans for infrastructure development or program expansion can significantly boost a university’s capacity for growth. Interview insights revealed that “Access to loans helps us to expedite construction projects, which would otherwise be delayed due to insufficient government funding.” Financial institutions can provide the necessary capital for building new campuses, upgrading technology, or expanding research capabilities. However, the risk of accumulating unsustainable debt was a concern among FGD participants, who stressed the need for thorough risk assessments before entering into borrowing agreements. Research by Altbach and Salmi (2011) supports this, indicating that while borrowing can drive rapid expansion, it must be managed prudently to avoid financial strain.\n\n• Constructing Buildings and Acquiring Material Assets: Financial autonomy facilitates the ability of universities to construct new facilities and acquire material assets, such as laboratory equipment and information technology infrastructure. An interviewee remarked, “With autonomy in construction decisions, we can directly invest in new buildings tailored to our needs, such as state-of-the-art labs.” This capacity enables universities to develop infrastructure that aligns with their academic objectives and research focus. Studies show that universities with control over their infrastructure investments are better positioned to create conducive learning environments (Salmi, 2009). However, without careful planning, there is a risk that resources may be disproportionately allocated to physical infrastructure at the expense of other academic priorities.\n\n• Imposing Tuition Fees on National Students: The power to determine tuition fees allows universities to balance their revenue needs with their mission of providing accessible education. According to a university administrator, “Tuition fees enable us to generate additional income that supports student services and research activities.” This autonomy can help institutions reduce reliance on government funding and allocate resources where they are most needed (Brezis, 2019). However, it also introduces the challenge of maintaining equity and access, as higher fees can limit the ability of low-income students to attend university. This concern is echoed in research by Johnstone (2017), who emphasizes the need for balancing financial sustainability with inclusivity in tuition fee policies.\n\nMajor Challenges:\n\n○ Lack of Financial Management Expertise: Interviews with university financial officers revealed a lack of expertise in budget planning and financial management as one of the critical obstacles in the transition to financial autonomy. A senior financial officer at a public university noted, \"Our institutions have always relied on government allocations, and the sudden shift to managing our budgets independently is a steep learning curve.\" This aligns with Ashcroft and Rayner (2021), who highlighted that newly autonomous institutions often struggle with budget forecasting and efficient allocation of funds.\n\n○ Dependence on Government Funding: Focus group discussions with university board members highlighted the challenge of moving away from state dependency. Participants noted that most Ethiopian universities have limited experience in generating revenue through research grants or partnerships with the private sector. One FGD participant emphasized, \"The concept of financial independence is still new. The public expects education to be free or heavily subsidized, making the introduction of tuition fees a challenge.\" This finding is consistent with the Ethiopian Ministry of Education’s (2021) report, which emphasizes that universities face difficulties in diversifying revenue sources amid societal resistance.\n\n○ Resistance to Imposing Tuition Fees: Interviews with student representatives revealed strong opposition to the idea of tuition fees, which could lead to protests and decreased enrollment rates. One student representative mentioned, \"Introducing fees will hurt the poor and undermine the accessibility of education. It’s not just about revenue; it’s a social contract.\" Such concerns mirror Teferra’s (2017) findings that introducing tuition fees in systems where free education is the norm often leads to backlash and enrollment challenges.\n\n\n5. Conclusion\n\nThe pursuit of autonomy in Ethiopian public universities reveals complex, interwoven challenges across institutional, administrative, academic, and financial dimensions. This study illustrates that achieving autonomy is a multidimensional endeavor, shaped by a range of political, financial, and structural factors that influence each aspect of university governance.\n\nInstitutional autonomy emerges as a foundational pillar, allowing universities to independently establish policies, set strategic priorities, and cultivate an environment of innovation and academic freedom. However, centralized government control restricts this autonomy, impacting governance, budget allocations, and strategic decisions. Political interference and financial dependence on state funding further constrain universities’ ability to act independently, aligning with Institutional Theory’s view on the constraints external pressures impose on organizational self-governance.\n\nAdministratively, the entrenched system of centralized oversight and historical governance practices challenge universities’ ability to exercise self-direction. Principal-Agent Theory captures this dynamic, with the government (principal) retaining substantial control over university administration, which limits university leaders’ decision-making power and fosters conditions for political interference. To move toward genuine autonomy, Ethiopian universities must establish governance frameworks that balance national educational objectives with institutional integrity, while protecting academic freedom from political influence.\n\nAcademically, the autonomy to design curricula and direct research is hindered by the need for standardization and compliance with national quality assurance policies. Institutional Theory highlights the constraints external standards impose, often limiting curriculum flexibility and responsiveness to local needs. This tension between standardization and institutional diversity restricts innovation in teaching and research, as universities prioritize conformity over contextual adaptability.\n\nFinancially, autonomy requires diversified funding strategies to reduce dependency on government resources. Resource Dependency Theory underscores the vulnerability inherent in relying heavily on state funding, which restricts universities’ operational flexibility and makes them susceptible to economic and political fluctuations. Without alternative revenue streams—such as private investments, industry partnerships, and research grants—universities face limitations in infrastructure development, research initiatives, and overall financial sustainability.\n\nAdvancing autonomy in Ethiopian public universities requires a holistic approach that addresses the barriers within each autonomy dimension, fostering an environment of resilience, diversity, and innovation. The study calls for collaborative stakeholder engagement involving government, university leadership, faculty, and students, facilitating open dialogue and mutual understanding to ensure policies reflect institutional needs and aspirations. Transparent policies and accountability mechanisms are critical to managing Principal-Agent conflicts, ensuring universities can operate autonomously while remaining aligned with national goals.\n\nAdditionally, sustainable financial strategies that include diversified revenue sources are essential to reducing dependency on government funding, thereby bolstering institutional resilience. Ethiopian universities should adopt a culture of continuous evaluation, adapting strategies to meet emerging challenges in higher education. While the path to autonomy is complex, it offers Ethiopian public universities an opportunity to redefine their roles as hubs of academic excellence and innovation. Establishing clear governance frameworks, empowering university leaders through training and involving stakeholders in policy development are vital steps forward. Enhancing academic freedom through flexible quality assurance mechanisms and fostering financial autonomy through partnerships and innovative funding models will help create a more autonomous, resilient, and responsive higher education system that meets the needs of students, faculty, and society alike.\n\n\nEthics and consent\n\nThe research adhered to rigorous ethical standards to protect participants and uphold the integrity of the research process. Written consent was obtained from all participants, who were thoroughly informed about the study’s nature, purpose, and potential risks prior to their participation. This process ensured that participants understood the study’s objectives, procedures, and their rights, including the right to withdraw at any time without consequence. The study complied with all ethical guidelines approved by the ethical review committee, and no waiver of consent was granted. If verbal consent had been employed, it would have been clearly documented, along with the rationale for this approach, requiring explicit approval from the ethics committee. However, written consent was utilized in this study to maintain stringent ethical standards, thereby ensuring participants were aware of their rights, including their ability to withdraw from the study at any time without repercussions (Orb, Eisenhauer, & Wynaden, 2001). Confidentiality and anonymity were strictly upheld throughout the research process. Identifying information was removed from transcripts, and data was securely stored to prevent unauthorized access. This approach was essential for safeguarding participants’ privacy and ensuring ethical conduct in the research (Wiles, 2012). The study received full ethical approval from the Institutional Review Board (IRB) of the College of Law and Governance, Hawassa University,which consists of five members. Approval was granted on December 10, 2023, under number GaDS- 116/2023. All procedures involving human participants were conducted in strict adherence to the Declaration of Helsinki to ensure the ethical integrity of the research.",
"appendix": "Data availability statement\n\nThe data supporting the findings of this study are fully included within the manuscript. No additional or supplementary datasets are available. However, access to certain data is subject to the following restrictions:\n\n• The data are proprietary and confidential, collected under agreements that limit sharing beyond the immediate research team.\n\n• Personal and sensitive information has been anonymized to ensure privacy and compliance with data protection regulations.\n\nFor transparency and replication purposes, the following datasets related to the study are available in public repositories:\n\n\n\n• Title: Autonomizing public universities in Ethiopia: exploring the potential challenges\n\nRepository Name: Zenodo\n\nDOI: https://doi.org/10.5281/zenodo.13918280\n\nCitation: Mohammed, A. A. (2024).\n\nThis project contains the following extended data\n\nConsent Form, Interview Guide, FGD Guide and Observation\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nInstitutional Review Board (IRB) Statement\n\nThe Institutional Review Board (IRB) provided approval for this study and did not impose specific conditions or restrictions regarding data sharing. The research adhered to all applicable ethical guidelines, ensuring that the rights and privacy of participants are protected throughout the research process.\n\nAccess Conditions\n\nRequests for access to the data should be directed to the corresponding author at awolali1989@gmil.com. Access may be granted under the following conditions:\n\n• The requester must provide a valid rationale for the data request, detailing the intended use of the data and how it aligns with the research objectives.\n\n• The requester must agree to adhere to all confidentiality and data protection protocols, including the commitment to not disclose any identifiable information and to use the data solely for the purposes specified in the access request. Any published work resulting from the use of this data should appropriately cite the original research.\n\n\nReferences\n\nAAU Official Website: Addis Ababa University. 2023. Reference Source\n\nAbebaw Y: What are the implications of ‘real’ university autonomy? University World News, African Edition; 2021. Reference Source\n\nAboye A: Political ideology and academic autonomy in Ethiopia. Journal of Comparative & International Higher Education. 2021; 13(4): 16–27. Publisher Full Text\n\nAddis Ababa University Financial Overview: 2023. Retrieved from Addis Ababa University Reports.\n\nAddis Ababa: Interview Addis Ababa University. 2023.\n\nAithal PS, Aithal S: Autonomy for universities excellence–challenges and opportunities. International Journal of Applied Engineering and Management Letters (IJAEML). 2019; 3(2): 36–50. Publisher Full Text\n\nAithal PS, Kumar PMS: Student performance and learning outcomes in higher education institutions. International Journal of Scientific Research and Modern Education. 2019; 4(1):1–12.\n\nAkalu GA: Higher Education in E thiopia: Expansion, Quality Assurance and Institutional Autonomy. High. Educ. Q. 2014; 68(4): 394–415. Publisher Full Text\n\nAlemayehu G, Yizengaw T: Challenges and opportunities in the implementation of higher education reforms in Ethiopia. Addis Ababa University Press; 2020.\n\nAltbach PG: Global perspectives on higher education. Johns Hopkins University Press; 2013.\n\nAltbach PG, Gumport PJ, Berdahl RO: American higher education in the twenty-first century: Social, political, and economic challenges. World Future Review (World Future Society). 2011.\n\nAltbach PG, Salmi J: The road to academic excellence: The making of world-class research universities. World Bank Publications; 2011. Publisher Full Text\n\nAltbach PG, de Wit H : The challenges of higher education in developing countries. Higher Education Journal. 2020; 79(3): 347–358.\n\nAMU Official Website: Arba Minch University Official Website. 2023. Reference Source\n\nArbaminch: Arba Minch University Official Website. 2023. Reference Source\n\nArbaminch: Arba Minch University Official Website. 2024. Reference Source\n\nAshcroft K, Rayner P: Autonomy and accountability in higher education: A global perspective. J. Educ. Policy. 2021; 36(5): 674–688.\n\nAssociation of American Colleges & Universities (AAC&U): Academic Freedom and Institutional Responsibility. AAC&U Website; 2022.\n\nBelgaroui H, Hamad M: The Role of Academic Autonomy in Higher Education: Strategic and Operational Independence. J. Educ. Adm. 2021; 59(2): 145–162.\n\nBennett L, Bane T, Tamayo J: Academic Freedom and the Evolving Landscape of Higher Education. Journal of Academic Ethics. 2020; 18(3): 249–267. Publisher Full Text\n\nBourgeois R, Nizet J: Resource dependency and organizational autonomy: A study of public universities. Routledge; 2019.\n\nBowen GA: Document analysis as a qualitative research method. Qual. Res. J. 2009; 9(2): 27–40. Publisher Full Text\n\nBoyer EL: Scholarship reconsidered: Priorities of the professoriate. Carnegie Foundation for the Advancement of Teaching; 1990.\n\nBraun V, Clarke V: Using thematic analysis in psychology. Qual. Res. Psychol. 2006; 3(2):77–101. Publisher Full Text\n\nBrezis ES: Higher education and economic development: the importance of building an adaptive capacity. Educ. Econ. 2019; 27(3): 271–287.\n\nCapital Ethiopia: Capital Ethiopia Newspaper. 2024. Reference Source\n\nCastelló-Climent A, Hidalgo-Cabrillana A: The role of educational quality and quantity in the process of economic development. Econ. Educ. Rev. 2012; 31(4): 391–409. Publisher Full Text\n\nCreswell JW: Qualitative inquiry and research design: Choosing among five approaches. 3rd ed.SAGE Publications; 2013.\n\nCreswell JW: Research Design: Qualitative, Quantitative, and Mixed Methods Approaches. 4th ed.Sage Publications; 2014.\n\nDiMaggio PJ, Powell WW: The iron cage revisited: Institutional isomorphism and collective rationality in organizational fields. Am. Sociol. Rev. 1983; 48(2): 147–160. Publisher Full Text\n\nEthiopian Ministry of Education: Annual Education Statistics. Ethiopian Ministry of Education; 2023.\n\nEthiopian Ministry of Education: Higher education policy reform in Ethiopia: A progress report. Addis Ababa: Ministry of Education; 2021.\n\nFeleke KM: The institutional impacts of financial inadequacy and financial inefficiency of public universities in Ethiopia: the case of Bahir Dar university. Bahir Dar Journal of Education. 2014; 14(1).\n\nFlick U: An introduction to qualitative research. 6th ed.SAGE Publications; 2018.\n\nGebru SG, Hondeghem A, Broucker B: Institutional Autonomy of Ethiopian Public Universities: An Application of the European University Autonomy Scorecard Methodology. Leuven University Press; 2020; 531–564.\n\nGetu E: Institutional Autonomy and Accountability Practices of Ethiopian First Generation Public Universities. Ethiopia: Jimma University; 2021; 14–36. Masters Thesis.\n\nGibbs GR: Analyzing qualitative data. 2nd ed.SAGE Publications; 2018.\n\nGonzalez A, de Silva P : Transformative leadership in globalized higher education. Educational Leadership Review. 2018; 19(1):45–61.\n\nGuri-Rosenblit S: Digital technologies in higher education: Sweeping expectations and actual effects. Nova Science Publishers; 2009.\n\nHawassa: Interview, Hawassa University. 2023.\n\nHawassa University Annual Report: Hawassa University Reports.2023.\n\nHawassa University Official Website: 2023. Reference Source\n\nHayward FM: Quality assurance in higher education in sub-Saharan Africa: Challenges and opportunities. Int. J. Educ. Dev. 2018; 60: 60–69.\n\nHemsley-Brown J, Oplatka I: Higher education consumer choice. Palgrave Macmillan; 2015.\n\nInternational Institute for Educational Planning (IIEP): Human resource management in higher education: Challenges in Africa. UNESCO Publishing; 2019.\n\nJemal A: Challenges in Internal Revenue Generation for Ethiopian Universities. Ethiopian Journal of Higher Education. 2023; 18(1): 112–130.\n\nJohnstone DB: Cost sharing in higher education: Tuition, financial assistance, and accessibility in a comparative perspective. Int. J. Educ. Dev. 2003; 23(4):403–410. Publisher Full Text\n\nJohnstone DB: Tuition fees, student loans, and higher education finance: Examining prospects for financial autonomy in universities. J. High. Educ. Policy Manag. 2017; 39(2): 167–180.\n\nJudith A, Stamenka M: Quality Assurance in Higher Education Across the World. Okebukola PA, Uvalić-Trumbić S, editors. Council for Higher Education Accreditation (CHEA); 2021.\n\nKehm BM: Global university rankings: Impacts and lessons for higher education in Europe. Eur. J. Educ. 2014; 49(1):102–112. Publisher Full Text\n\nKezar A: Understanding and facilitating organizational change in the 21st century: Recent research and conceptualizations. Wiley; 2013.\n\nKifle S: Public university autonomy and quality education: Opportunities and challenges. Consortium of Ethiopian Public Universities (CEPU); 2022. Reference Source\n\nKrause K-L, Hartley R, McEwan T: Teaching in Higher Education: A Research Perspective. Routledge; 2020.\n\nMaassen P: Higher Education Research: The Hourglass Structure and Its Implications. US. Teichler T, Sadlak J, editors. Pergamon and IAU Press; 2000.\n\nMaassen P, Gornitzka Å, Fumasoli T: University reform and institutional autonomy: A framework for analysing the living autonomy. High. Educ. Q. 2017; 71(3): 239–250. Publisher Full Text\n\nMarginson: Higher Education and the Common Good. Melbourne: Melbourne University Publishing; 2016.\n\nMarmolejo F: Trends in higher education: Challenges and opportunities for internationalization. Journal of Global Policy and Strategy. 2016; 4(2):15–28.\n\nMekonnen GT, Kilpatrick S, Kenny J: Constrained autonomy: academics and institutional leaders empowerment in Ethiopia in the context of the Bologna Process. J. Furth. High. Educ. 2022; 46(2): 143–158. Publisher Full Text\n\nMeyer JW, Rowan B: Institutionalized organizations: Formal structure as myth and ceremony. Am. J. Sociol. 1977; 83(2): 340–363. Publisher Full Text\n\nMiles MB, Huberman AM, Saldana J: Qualitative data analysis: A methods sourcebook. 3rd ed.SAGE Publications; 2014.\n\nMohammed AA: Consent Form, Interview Guide, FGD Guide and Observation Check List. Zenodo. 2024. Publisher Full Text\n\nNussbaum MC: The Academy’s Role in the Era of Authoritarianism: Protecting Academic Freedom. Perspect. Polit. 2021; 19(3): 676–683. Publisher Full Text\n\nObservation: Researcher’s on site observation on selected public universities. 2023.\n\nOrb A, Eisenhauer L, Wynaden D: Ethics in qualitative research. J. Nurs. Scholarsh. 2001; 33(1): 93–96. Publisher Full Text\n\nPatton MQ: Qualitative research and evaluation methods. 4th ed.SAGE Publications; 2015.\n\nPfeffer J, Salancik GR: The external control of organizations: A resource dependence perspective. Stanford University Press; 2003.\n\nSalmi J: Constructing knowledge societies: New challenges for tertiary education. vol. 28. . World Bank; 2003; pp. 65–69 . Publisher Full Text\n\nSalmi J: The challenge of establishing world-class universities. World Bank Publications; 2009.\n\nSalmi J, Saroyan A: League Tables as Policy Instruments: Uses and Misuses. Higher Education Management and Policy. 2007; 19(2): 1–38. OECD Publishing. Publisher Full Text\n\nShattock M: Managing successful universities. Open University Press; 2019.\n\nSilverman D: Qualitative research. 5th ed.Sage; 2020.\n\nSunandar W, Imron A: Leadership practices in higher education institutions: Insights from Southeast Asia. Asian Journal of Higher Education Research. 2019; 7(3):124–136.\n\nTadesse M: The Impact of Financial Constraints on Higher Education Quality in Ethiopia. Ethiopian Journal of Educational Research. 2022; 24(3): 55–70.\n\nTeferra D: The Challenges of Governance in Rapidly Expanding Higher Education Systems in Africa: Ethiopia in Focus. High Educ. Pol. 2018; 31(1): 5–21.\n\nTeferra D: The evolving landscape of higher education in Africa: Challenges and opportunities. J. High. Educ. Afr. 2017; 15(1): 1–15.\n\nThe Reporter: The Reporter Newspaper. 2023. Reference Source\n\nTrow M: Reflections on the transition from elite to mass to universal access: Forms and phases of higher education in modern societies since WWII. Int. J. High. Educ. 1996; 1(1):5–22.\n\nTrowler V: Research and Academic Freedom: An International Perspective. High. Educ. Res. Dev. 2022; 41(2): 387–399. Publisher Full Text\n\nUniversity World News: The perils and promises of becoming an autonomous university.2023. Reference Source\n\nVeugelers R: Towards a multipolar science world: Trends and impact. Scientometrics. 2009; 82(3): 495–511.\n\nWiles R: What Are Qualitative Research Ethics?Becker ARJA, Lauder MJH, editors. The Ethics of Research with Children: A Handbook of Research Ethics. New York: Routledge; 2012; pp. 69–83.\n\nWorld Bank: Benchmarking the Governance of Tertiary Education Systems. The World Bank Group; 2012. Reference Source\n\nWorld Bank: World Bank Group Reports on Ethiopia. 2020.\n\nYin RK: Case study research and applications: Design and methods. 6th ed.SAGE Publications; 2018."
}
|
[
{
"id": "343758",
"date": "24 Dec 2024",
"name": "Degwale Gebeyehu Belay",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral Comments\nThe title needs to be revised to more accurately reflect the roles and challenges associated with autonomy. The rationale behind the study is unclear. What is the current state of autonomy in Ethiopian universities? Is autonomy primarily driven by government interest, university interest, or both? Clarifying this question would help to contextualize the author’s discussion of principal-agent theory. Additionally, it is important to clarify what type of autonomy is being sought by both the government and universities in Ethiopia. It should also be made clear that academic freedom is distinct from autonomy. In developing countries like Ethiopia, autonomy may not necessarily guarantee academic freedom. Therefore, the researcher should provide a nuanced discussion of these concepts and explore how academic freedom intersects with autonomy, particularly in the context of universities striving for greater autonomy. The study objectives should be consolidated into a single, clear objective focusing on the \"challenges\" of autonomy. Consider adding other relevant objectives as necessary. The theoretical framework of the study will benefit from further development once the context is clarified and the objectives are refined. The methodology section requires improvement:\nObservation is listed as a data collection tool, but it seems that document analysis was actually conducted. Please correct this. The Focus Group Discussions (FGDs) should clearly specify the number of FGDs conducted, as well as the number of participants in each group. In the methodology, it states that FGDs were conducted with faculty members and students, but in the discussion, board members are referred to as the discussants. This needs to be reconciled for consistency. The sampling technique used to select participants should be clearly explained. Table 1 (study participants) should provide more detailed information, such as the specific departments/faculties of the deans or directors and the rationale for their selection.\n\nResults Section\nThe results section is fragmented and lacks coherence. It needs to be more structured to improve flow and readability. The citation format for interview and FGD results is inconsistent and unclear. Citations should provide clear information about the informant, their affiliation, and the date of the interview/FGD. In some places, in-text citations are provided unnecessarily (e.g., page 7; Mohammed, 2024). Please review and adjust accordingly. Some direct quotations appear to include the author's own explanations and descriptions, which is incorrect. Please ensure quotations are verbatim. The article struggles to distinguish between the challenges of becoming autonomous and the challenges that may arise after autonomy is achieved. Clarification is needed on this aspect. The article lacks a clear and comprehensive literature review, both empirical and conceptual. A stronger review would enhance the foundation of the study. The reporting style should be revised. It would be more effective to first describe the roles of autonomy, followed by a discussion of the challenges. This will improve clarity and reduce repetition.\nSuggested structure:\n\n4.1. Roles 4.2. Challenges\n4.2.1. Administrative Challenges 4.2.2. Institutional Challenges\n\nThis structure would enhance the readability of the paper.\nAddis Ababa University has already achieved autonomy, yet there is no clear distinction in the key informants from this university compared to those from the other sample universities. This needs to be addressed. At times, the paper seems to evaluate the practice of university autonomy, while at other times it focuses on the challenges universities face (note that all universities except Addis Ababa are not yet autonomous). Sometimes, it also discusses the potential challenges universities may face if they become autonomous. The focus of the study needs to be clearer and framed consistently. A SWOT analysis could be valuable to assess the fertile ground for autonomy in Ethiopian universities. This analysis would provide insight into the strengths, weaknesses, opportunities, and threats related to autonomy in the context of these institutions.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "347609",
"date": "28 Dec 2024",
"name": "Solomon Gebreyohans Gebru",
"expertise": [
"Reviewer Expertise Higher education system and institution"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript addresses significant issues related to the pursuit of autonomy in Ethiopian public universities, providing analysis of the challenges public universities face in achieving autonomy, especially in institutional, administrative, academic and financial dimensions. The work is comprehensive and thorough, with a clear connection to established theoretical frameworks like Resource Dependency Theory (RDT) and Institutional Theory, as well as relevant studies in higher education governance. Overall, the manuscript provides a valuable contribution to understanding the complexities of autonomy in Ethiopian public universities. While the manuscript is overall well-organized and addresses important issues, there are several areas that need further attention to enhance the quality, clarity, and academic rigor of the work. These areas include strengthening the study’s methodological transparency, tuning the argument vis-à-vis the research objective, and ensuring consistency in citations.\nGeneral Comments\nIs the work clearly and accurately presented and does it cite the current literature? The work is generally well-presented and cites relevant current literature. However, one important concern. On page 4 (paragraph 6&7), the author claims that while previous studies have explored various aspects of higher education in Ethiopia, such as institutional autonomy, expansion, quality assurance, and governance, none of them have focused on examining the specific challenges related to the most recent initiative by the Ethiopian government to grant autonomy to universities. This recent initiative appears to be a new policy or reform effort, and the challenges it presents—whether administrative, academic, financial, or otherwise—have not yet been comprehensively analyzed in the existing body of research. The study aims to fill this gap by focusing explicitly on the potential challenges arising from this current governmental effort. Yet, the manuscript does not provide sufficient detail about the new initiative, including its goals, policies, and implementation framework as well as whether the challenges discussed are connected to this specific reform effort. To rectify this issue, the author should:\nProvide Clear Context: Clearly explain the new initiative or reform by the Ethiopian government to grant autonomy to universities, including its specific goals, policies, and the framework for its implementation. This will help readers understand the reform effort being discussed and why it is considered recent. Link Challenges to the Reform Effort: Ensure that the challenges highlighted in the study (administrative, academic, financial, etc.) are explicitly connected to the current reform initiative. The author should demonstrate how these challenges are unique to or exacerbated by the new policy or initiative. Cite Relevant Literature: Include references to any government documents, official reports, or policy papers related to the reform initiative. This will provide a stronger foundation for the claim that previous studies have not yet fully addressed the challenges of this specific policy.\n\nIs the study design appropriate and is the work technically sound? The study design is appropriate for addressing the research questions and is technically sound, with a focus on qualitative interviews. However, some methodological details need to be expanded for clarity and transparency. For example, the author needs to provide more details on how he selected the universities, the interviewees, and the specific criteria used for these decisions. On page 6, paragraph 4: The author should provide a clear justification for selecting Addis Ababa University, Hawassa University, and Arba Minch University, especially since there are several first-generation universities in Ethiopia. It would strengthen the study to explain why these particular universities were chosen and how their characteristics make them suitable for comparison. This would enhance the transparency and relevance of the selection criteria, allowing readers to understand the study's focus. Are sufficient details of methods and analysis provided to allow replication by others? While the methodology section provides a basic overview, it lacks specific details on participant selection, data collection, and analysis procedures. More transparency is needed to allow full replication. The author should clarify the rationale behind selecting the specific number and types of participants for the study. It would be beneficial to explain why certain positions were prioritized and why the total number of participants was limited to 59. Justifying the selection criteria would strengthen the study's methodology and provide readers with a better understanding of how these participants contribute to addressing the research questions.\nAre all the source data underlying the results available to ensure full reproducibility? As mentioned earlier, details about interview transcripts and participant which could enhance reproducibility is not provided. More details on participant selection and the interview process would improve the transparency of the methodology. The author should provide specific details about when the data were collected. Including this information is crucial for the reader to understand the timeframe of the study, the relevance of the findings. This also helps with assessing the potential context and temporal factors that could influence the results. Since the methodology did not mention that participants would be cited anonymously, the author should provide more specific information about the interviewees. This could include their names, positions, and the institutions where the interviews occurred, along with the date. The author also needs to ensure consistent citation styles for interviews and key informant inputs. For example: Clearly distinguish between interviews and key informant interviews (KII). Include details such as date, role, and institution to enhance transparency. Generally, the author should ensure that the citation format is consistent with the methodology section and properly identifies the source of the quote. When citing direct quotations from published sources, page numbers should be included to guide readers. The author should also explain about the credibility and validity of findings. Adding more information on how data were analyzed, particularly any coding or categorization techniques used.\nAre the conclusions drawn adequately supported by the results? While the conclusions broadly reflect the study's findings, a more direct reference to how the data specifically supports each claim would improve clarity and ensure stronger alignment Page by page comments On page 3, the following statements: “A high degree of administrative autonomy enables HEIs to cultivate an environment that prioritizes innovation, efficiency, and responsiveness to the needs of students and faculty alike (Gonzalez & de Silva, 2018).” (on paragraph 4) “When universities possess academic autonomy, they can better adapt their offerings to evolving societal and labor market demands, thus enhancing their relevance and impact (Trow, 1996).” (on Paragraph 5) “Financial autonomy not only enables institutions to withstand fluctuations in government funding but also fosters a culture of accountability and transparency in resource allocation (Johnstone, 2003)” (on paragraph 6) effectively highlight the importance of different types of autonomy—administrative, academic, and financial—in higher education institutions (HEIs). However, it would strengthen the review to address any potential limitations or critiques of these arguments, especially in relation to the Ethiopian context. On page 6, paragraph 5, the described approach is more accurately categorized as triangulation rather than a comparative technique. The focus here is not on comparing distinct cases or groups but rather on validating and contrasting insights from various data sources. Suggestion This study employed a triangulation approach by systematically comparing data from interviews, observations, and document analysis to validate findings and identify gaps between policy intentions and actual practices. Observational data collected using standardized checklists were cross-referenced with university autonomy guidelines, reports, and administrative documents. This methodological triangulation helped to ensure a comprehensive understanding of the phenomenon (Miles, Huberman, & Saldana, 2014; Flick, 2018).\nOn page 6, last paragraph, the statement should clearly indicate that the emphasis on institutional autonomy is derived from the perceptions of the study participants. Additionally, avoid phrases like \"our university,\" which could introduce bias or lack of objectivity. The same is true on page 9 paragraph 1. The use of \"our\" implies a personal involvement or bias, which is not appropriate in formal academic writing unless quoting participants directly and even then, the context needs to be clear. On page 9, paragraph 3, there seems to be a disconnect between the literature (Maassen et al., 2017) and the participant quotation. To improve this, the author should explicitly link the participants' views to the relevant literature, showing how the participants' perceptions align with or challenge existing theories. The connection should be made clear to strengthen the argument and provide context for the participants' views. On page 10, paragraph 1, the statement does raise a concern regarding its clarity and reliability. It makes a broad claim about the outcomes of past university initiatives in Ethiopia without citing specific evidence or sources to support it. The author should strengthen this statement by providing references to specific documents, reports, or studies that support the claim. It's important to clarify which initiatives are being referenced, what specific data or findings were analyzed, and how these led to the conclusions about poor management, financial losses, and reputational risks. On page 10, Reading meeting minutes as observation: Reading meeting minutes does not qualify as observation but rather document analysis. Observations usually involve direct engagement with or witnessing real-time activities. The author should adjust the terminology to reflect the actual method. On Page 10, Location/institution: The author should indicate the specific institution or meeting context where the observation took place. This adds credibility and precision to the claim. On page 11 (paragraph 5&6): the two paragraphs are complementary, but the connection between tighter government control and political appointments could be made more explicit. The author should use linking phrases to establish coherence. On page 13 (last paragraph), you present contrasting views on academic freedom and curriculum flexibility. The two perspectives highlight a tension between theoretical principles and practical realities, where academic freedom is lauded but its application is hampered by institutional processes. To improve clarity and coherence, consider explicitly addressing this tension. You might frame the first statement as an ideal or policy aspiration and the second as a practical challenge observed in implementation. This will help reconcile the apparent contradiction and provide a balanced discussion.\nOn page 15 (paragraph 1) The author should clarify how the Ethiopian government's new higher education proclamation is perceived by participants in the study, specifically regarding its potential to cause excessive standardization. It would also be helpful to explain how this aligns with or extends the concerns raised in previous research, such as that of Aboye (2021). Providing specific examples or direct quotes from interviewees could strengthen this argument. On page 15, paragraph 3, I recommend asking the author to clarify why key informants emphasized the lack of centralized quality assurance despite existing oversight mechanisms in Ethiopia. It would be useful to explore whether there are specific gaps in the implementation of these mechanisms that might have led to these concerns. On page 15, paragraph 5, the phrase \"potentially undermining institutional autonomy\" indicates that the challenges caused by the expansion might lead to a situation where universities’ ability to function independently, without undue interference from the government, could be compromised. I would recommend that the author further clarify how the rapid expansion has affected autonomy in terms of governance. Specifically, the author should elaborate on whether informants advocate for increased autonomy for universities in response to the pressure on governance models, or if they view more governmental oversight as necessary to address governance challenges.\nOn page 15-16 (end and beginning paragraphs) there is a lack of connection between the initial discussion of academic autonomy and the points listed following the paragraph on pages 15-16. The author shifts from a general statement about autonomy to specific points (such as admissions, program initiation, and quality assurance) without clearly linking them back to the overall theme of autonomy. The same is true for paragraph 4 and the subsequent lists on page 20.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1416
|
https://f1000research.com/articles/13-801/v1
|
16 Jul 24
|
{
"type": "Research Article",
"title": "Death anxiety scale (DAS): internal structure and factorial invariance in Peruvian adults",
"authors": [
"Carlos De La Cruz-Valdiviano",
"Aldo Bazán-Ramirez",
"Lincol Olivas-Ugarte",
"Juan Quijano-Pacheco",
"Aldo Bazán-Ramirez",
"Lincol Olivas-Ugarte",
"Juan Quijano-Pacheco"
],
"abstract": "Background Studies have this reported the presence of death anxiety, ranging from near-death experiences to physically ill people, to a simple thought about death, as well as when it is associated with states of loneliness. The Templer’s Death Anxiety Scale (DAS), based on Eysenk’s incubation theory, has been adapted and validated in different contexts and is still insufficient in countries such as Peru. This study aimed to determine the psychometric properties of the DAS, its internal structure, and factorial invariance.\n\nMethods An online scale was used in 1248 Peruvians aged between 18 and 70 years (M= 27.37, SD= 11.29) from all regions. DAS was validated using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, measurement invariance, and internal consistency (reliability).\n\nResults Psychometric properties were found with adequate values in its structure and validity based on the internal structure through exploratory factor analysis, where it was found that the components of the scale are interrelated and the data matrix is factorizable. model of three specific factors and a general factor is presented, which is consistent with the theory and has practical utility, revealing adequate statistical values that reflect acceptable levels of reliability. Finally, there was fairness according to sex and age group of the scale by means of factorial invariance analysis.\n\nConclusions Our results indicate adequate psychometric properties and facilitate a better data collection process for future research.",
"keywords": [
"death anxiety",
"validity",
"reliability",
"fairness/equity",
"adults."
],
"content": "1. Introduction\n\nDeath is a universal human fact,1 and people experience death anxiety in different ways, and the way they express it is usually particular according to sociodemographic variables such as age, sex, religion, among others, or psychological variables, such as self-esteem, personality, mood, or coping styles1,2 In this regard, other authors3 pointed out that there are two main variables: mental health and near-death experiences (accidents or terminal illness) that influence the degree of death anxiety. However, Tomás-Sábado and Gómez-Benito2 argued that death anxiety occurs both in people who are physically ill and in those who think about death.\n\nIn this context, in 2020, according to the Pan American Health Organization/World Health Organization,4 the spread of SARS-Cov-2 was declared a public health emergency, known worldwide as COVID-19. Orús5 mentioned that about 6.3 million people died due to this virus as of June 12, 2022. Due to its appearance, several measures have been taken in this regard, and people’s daily lives have been altered in different dimensions, such as work performance, family and social ties, educational activities, economic instability, and health conditions, which are factors that become indicators of anxiety among other psychological repercussions. According to the PAHO/WHO6 during the first year of the pandemic, the prevalence of anxiety or fear of death has increased by 25% worldwide, with young people being part of the most affected population. Thus, nowadays, all people live in a very different context to the one they used to know and thus find different reactions to it, as life conditions are altered, which is why many people have suffered from this silent disorder that is anxiety, which is a recurrent topic in research since its features are visible in society.7\n\nA study conducted by the University of Bristol found that the number of young people with anxiety increased from 13% to 24%.8 Thus, death anxiety is a reaction generated by the sensation of risk, whether real or imaginary, that originates from environmental stimuli.9 Taking as a reference what has already been mentioned, it is understandable that when the routine cycle of people’s lives is altered, these have an impact on more internal levels such as ways of thinking, habits that have changed, and the intensity of emotions, which is directly reflected in the behavior that in the end is the manifestation of how each person has internalized this situation. In Metropolitan Lima, where the main districts affected by the pandemic are located because of the high level of contagion and the numerous deaths that have occurred, the general population is taken as a reference for the pandemic reality in order to determine anxiety as a result of this context.10 It is, therefore, necessary for specialists to have a reliable instrument with which to obtain real results and thus be able to perform an optimal screening in order to analyze the levels of anxiety in the Peruvian population.\n\nThe Death Anxiety Scale (DAS) created by Templer11 and authorized by its authors in the Mexican version12 was used to measure these variables. Therefore, given that an instrument would be very helpful in exploring what has already been explained, the following question was formulated: What is the evidence of validity, reliability, and fairness of the death anxiety scale (DAS-1) in Peruvian adults, 2022? At the methodological level, the study provides rigor in terms of validity, reliability, equity, and psychometric characteristics of an instrument for Peruvian adults. Practically, it encourages professionals who deal with mental health to develop innovative research where standardized, valid, and reliable instruments need to be applied as a screening prior to specialized care. This results in death anxiety assessments relevant to the cultural context in which they are applied. Although Templer’s DAS has resisted the test of time as a commonly used index to capture the conscious experience of death anxiety, a continued evaluation of how the DAS translates in specific countries is required with an assessment in relation to other death construct tools,13 such as the population of adults aged 18 to 70 years, which in Peru make up the majority of the population14 that will lead the way to the country’s development. At the same time, it is relevant because it focuses on one of the most important topics, such as anxiety that the Peruvian adult population may be related to the post-pandemic context. Likewise, it will serve as a background for prospective studies whose objective is to study the same variable, and finally, its purpose is to support early intervention for events that could have serious consequences for this population.\n\nPsychometric tests provide measurable and objective data that provides an overview of the performance of an individual or population. This scale provides a degree of scientific reliability and objective recruitment process. In addition, because it is a standardized test, it reflects accurate information. Therefore, the general objective was to analyze the psychometric properties of the Death Anxiety Scale (DAS) in the Peruvian adult population. Accordingly, following a sequential order, the specific objectives were formulated as follows: 1) to verify the metric quality of the items, and 2) to examine the evidence of validity based on of the internal structure, 3) to examine the evidence of reliability, and finally 4) to examine the evidence of fairness according to sex and age group of the DAS Scale in Peruvian adults.\n\nRivera and Montero12 carried out an adaptation in older adults and university students from Mexico; three dimensions were obtained in each group, and internal consistency was.86 and.83, respectively. Lopez-Castedo et al.15 analyzed patients with ischemic heart disease in Spain, finding positive correlation corrected item-total correlation in all items (0.32 and 0.54). Four factors were identified that together explained 51.85% of the variance in the data, while the reliability values were high (0.77). Resett et al16 examined 859 adults in Argentina. Factor analyses showed a bifactor structure with higher adequacy than a unifactor structure. These findings allow us to argue that the scale showed evidence of validity and reliability (.80) for that country.\n\nIn Peru, few studies have been conducted on death anxiety; in Trujillo, 50 hospitalized patients found that it is negatively related to mental adjustment to cancer; that is, the greater the mental adjustment to cancer, the lower the anxiety about death.17 Peñaloza18 analyzed the content validity of health personnel in Lima. AFC explains the three-factor model. The correlation with PIL-TEST was strongly negative (rho = − .630). Reliability by internal consistency through α and ω = .95. Analysis of invariance by sex indicated that the scores differed between men and women. In addition, Graus19 in older adults in Trujillo by confirmatory factor analysis, and reliability by internal consistency (.93) was very good. Rodriguez,20 in older adults in Chimbote, obtained reliability through ω and gave.81 for fear of agony or illness, .79 for fear of life coming to an end and.90 for fear of death. The results indicated that the scores ranged from acceptable to very good.\n\nFor RAE,21 anxiety is a situation of mood agitation, usually a state of fear associated with various diseases. According to Limonero22 fear indicates an expected reaction to the threat posed by anxiety-provoking events. It refers to a target that causes a bisector of discomfort, such as instability, restlessness, and fussiness, in the face of a surprise. Anxiety is a state of unconscious emotion, such as undefined despair.\n\nHamilton23 notes that fear can be present within normality or illness. Similarly, anxiety presents with a variety of symptoms, including cardiovascular pain, abdominal pain, dyspnea, and mental, cognitive, or subjective symptoms. The present work is based on Eysenck’s incubation theory.24 This, in turn, is based on classical test theory.25\n\n\n2. Methods\n\nThe sample consisted of 1248 Peruvian adults between 18 and 70 years of age (Arithmetic Mean [M] = 27.37, Standard Deviation [SD] = 11.29) from all regions of Peru. To select this sample, non-probabilistic convenience sampling was used, taking into account the corresponding inclusion and exclusion criteria.26–28 According to Comrey and Lee,29 a sample size of at least 100 is considered poor, and a sample size greater than or equal to 1000 is considered excellent.\n\nThe following inclusion criteria were established for the selection of participants: adults between the aforementioned ages residing in the Peruvian territory; those who would respond favorably to informed consent; those who had completed the responses to the instruments in Google Forms through the online link that was sent to them. Once the responses to the Google Form were obtained, the number of subjects was 1288. However, after careful review, 40 individuals were eliminated (19 said they were retired, widowed, or divorced, all under 20 years of age; 10 were born or lived in another country; 11 did not complete their answers) to avoid possible bias in the information. Those between 18 and 30 years of age stand out (39.9% men and 30% women), and in terms of place of residence, 40.1% of men and 36.5% of women live in the Department of Lima.\n\nSelf-administered online surveys were conducted using a written questionnaire and distributed by e-mail.30 The Death Anxiety Scale (DAS -1) was created by Donald I. Templer in the United States in 1970,11 where its application was individual and collective. Later, in 2002, it was adapted and translated into Spanish by Tómas Sábado and Gómez-Benito; in 2010, it was adapted and translated by Rivera y Montero into Mexican Spanish. In Peru, adaptation was given in 2016 in Trujillo by Graus.19 The time to consider is 10 to 15 min, while its administration is from 18 to 85 years of age. It is composed of 15 items with four Likert-type options.70 The items of this scale consider statements related to concepts related to death and their emotional repercussions on people, considering their impact on them. Initially, there were true and false response options; however, the dichotomous alternatives were modified by alternatives on a Likert scale with the objective of allowing a better variability in the responses that reflects what people feel or think in relation to death, thus improving the internal consistency of the scale itself. Scores were obtained using sums or averages. The participants provided four types of answers on a Likert scale: never or almost never (1), sometimes (2), most of the time (3), and all the time (4), with a minimum score of 15 (low anxiety) and 60 (high anxiety). In dimension I: Fear of agony or pathology, the minimum score was 5, and the highest was 20. In dimension II: Fear of life coming to an end, the minimum score was 7, and the highest was 28. Finally, dimension III: Fear of death, the minimum score is 3, and the highest is 12.\n\nThe instrument has psychometric characteristics verified in the United States and Spain, with Cronbach’s alpha fluctuating between .76 and .87 and a fairly good retest security, r = .71 and r = .84.12 Its construct value has been extensively studied, and its partnership has been defined with many psychological variants, such as depression and anxiety (r = .38 and r = .48, respectively).12,31 However, studies of its factorial composition are more contradictory in the analysis, sample, and cultural setting in which it is used.\n\nTo carry out the study, the necessary permission was requested from the author in order to be able to measure the variable under analysis. Then, the online survey form was disseminated through the Google Forms application in which informed consent, sociodemographic data, and the measurement instrument were included, and the link to the form was sent to individuals who met the requirements of the inclusion criteria for their participation. They were applied through social networks, such as Facebook and WhatsApp. They were also sent by electronic correspondence, prioritizing the authorization of the same for execution, emphasizing anonymity, privacy, and voluntary collaboration. Finally, the responses of individuals who did not meet the sample profile were not considered, and the exploration was carried out correctly using statistical programs.\n\nIn accordance with the World Medical Association (WMA) regarding the Declaration of Helsinki,32 specifically related to medical research on human beings, care was taken to consider primarily the health of the subject, precisely this work is oriented to favor conditions that promote their welfare (avoiding damage to their health), while ensuring and promoting satisfaction with the life and rights of those, with the purpose of contributing to screenings that facilitate diagnoses, preventive interventions and quality of treatments. The protocol was submitted for consideration, comment, guidance and approval by the Research Ethics Committee of the Cesar Vallejo University (Dictamen 070-CEI-EPM-UCV-2022)71,70 on September 28, 2022, after which the research could be carried out The participants were previously informed about the nature of the questionnaires, the importance of the study and the guarantee of their anonymity, then, regarding informed consent, the participants responded to their agreement via online.33 Likewise, the study was carried out taking into account the authors cited, so that any type of plagiarism was avoided.\n\nOnce the survey application was finished, the participants’ responses were downloaded into a Microsoft Excel spreadsheet to prepare the database. This information was then exported for statistical processing using the free program, RStudio version 4.3. The data were analyzed as follows: First, preliminary statistical analysis of the items was performed using the psych package.34 Statistics such as the mean (M), standard deviation (SD), coefficients of asymmetry (g1 = [-1.5; 1.5]), kurtosis (g2 = [-1.5; 1.5]),35,36 corrected homogeneity index (CHI ≥ .30),37 and communalities (h2 ≥ .40)38 were examined. Additionally, the polychoric correlation matrix (|r|= [.30; .90]) was extracted.39,40\n\nSecond, exploratory factor analysis (EFA) was performed using the psych and parameter package.41 The polychoric correlation matrix was used as input, with the purpose of determining the underlying structure of the DAS Scale. Previously, the assumptions of the EFA were verified: matrix determinant (|A| ≈ 0), Kaiser-Meyer-Olkin sample adequacy test (KMO ≥ .80), and Bartlett’s test of sphericity (p< .001).42 The following extraction methods were used: parallel analysis, optimal coordinates, and the Kaiser-Gutman rule. Likewise, the method of minimum residual estimation (Minres) was applied in combination with the oblimin rotation method.43 Finally, factor loadings (λ ≥ .30) and interfactorial correlations (φ ≥ .50) were examined.40,44–46\n\nThird, confirmatory factor analysis (CFA) was performed using the Lavaan package.47 The polychoric correlation matrix was used as the input because the data did not correspond to continuous variables with a normal distribution.48 In addition, the Weighted Least Squares with mean and variance adjusted variance (WLSMV) estimator was applied due to the ordinal nature of the items.49,50 Additionally, different factor structures were tested, as this is a good practice in psychometric studies.51 Different fit indices were used for model evaluation, such as chi-square (χ2, p < .05), Comparative Fit Index (CFI ≥ .94), Tucker-Lewis indices (TLI ≥ .94), standardized root mean square residual (SRMR ≤ .08), Root Mean Square Error of Approximation (RMSEA ≤ .07)52 and RMSEA confidence intervals (Li ≤ .05 and Ls ≤ .10). In addition, because χ2 is sensitive to sample size, the chi-square ratio over degrees of freedom (χ2/gl ≤ 5) was evaluated.53\n\nIn addition, specific indices for the bifactor models were examined. Likewise, the analysis of the indexes of the second-order model was considered, for which a Schmid-Leiman transformation54 was performed, allowing the variance of each factor to be estimated,55 both of which were processed using the EFA tool package.56 The following were considered as indicators of: unidimensionality: The conjunction of the magnitudes of the hierarchical ω coefficient for the overall factor (ωH > .80),57 of the hierarchical omega coefficient for the specific factors (ωhs ≥ .30) (Smits et al., 2014),58 the construct replicability coefficient (H > .90),59 common variance explained (ECV >.60), and percentage of uncontaminated correlations (PUC < .80).57 Finally, the percentage variance of the factors (ωH2, ωhs2) was calculated as evidence of the instrument’s explanatory power.44\n\nFourth, evidence of reliability was examined using the internal consistency method, quantifying its magnitude with the omega coefficient (ω) for multidimensional scales,60 appropriate for congeneric measures,61,62 and values ≥ .8063 were taken as the conventional cut-off point. Fifth, evidence of equity was evaluated by means of a factorial equivalence analysis according to sex and age group,64 using the semTools package.65 Four progressive levels of invariance were considered: 1) configural invariance (unrestricted), 2) metric invariance (factor loadings), 3) strong invariance (loadings and intercepts), and 4) strict invariance (loadings, intercepts, and residuals), taking the changes in CFI (ΔCFI ≤ .010), RMSEA (ΔRMSEA ≤ .015), and SRMR (ΔSRMR ≤ .030)66,67 to determine the interpretability of the items by the examinees68 and the equivalence of the scores obtained in the test, regardless of the participants’ membership.69\n\n\n3. Results\n\nAs Table 1 shows, for the most part, the DAS Scale items meet the parameters previously established to claim that the data matrix can be reduced to a smaller set of latent factors: the magnitudes of the correlations|r|= [.30–.90], corrected homogeneity index (CHI ≥ .30), and communalities (h2 ≥ .40). Therefore, the metric quality of the DAS items was verified for inclusion in the AFE.\n\nAs shown in Table 2, the AFE assumptions were previously verified: matrix determinant = .001, KMO test = .92, and Bartlett’s test of sphericity was statistically significant (p < .001), indicating that the variables are interrelated and that the data matrix is factorizable. Therefore, the procedure was repeated. The 15 items were then grouped into three factors with a total cumulative variance of 53.3%. Furthermore, the magnitudes of the interfactorial loadings (ϕ) [.40, .50] were consistent with an oblique three-factor correlated model. However, two items were discarded: item A9 (“I am afraid of dying a painful death”) for presenting very similar factor loadings in more than one factor (F1 = .32, F2 = .25, F3 = .33), and item A14 (“I am horrified to see a corpse”) for presenting low factor loadings (λ <.30). Consequently, we proceeded to run the CFA with only the other 13 remaining items.\n\nFigure 1 shows the three specified models that were tested to determine the best measurement model to fit the data: Model 1 = Correlated factors, Model 2 = Second order, Model 3 = Two-factor. However, the decision on the most plausible structure was made following not only statistical, but also theoretical, methodological, and ultimately practical criteria.\n\nNote: Model 1 = Correlated factors; Model 2 = Second order; Model 3 = Two factors; G = General Factor; F1 = Factor 1; F2 = Factor 2; F3 = Factor 3.\n\nTable 3 shows that the three proposed models obtained adequate fit indexes: CFI ≥ .94, TLI ≥ .94, SRMR ≤ .08, RMSEA ≤ .07. Although they present differences, they are not relevant. However, in mathematical terms, it is clear that model 3 shows better relative fit indexes (χ2/gl = 4.95 < 5). Therefore, the specific indexes for a bifactor model were further examined. The conjunction of the values was as follows: the hierarchical omega coefficient for the general factor (ωH > .80), the hierarchical omega coefficient for the specific factors (ωhs ≥ .30), the construct replicability coefficient (H > .90), the common variance explained (ECV > .60), and the percentage of uncontaminated correlations (PUC < .80) allow us to affirm the existence of a general factor that empirically justifies obtaining an overall score for the DAS Scale, with a proportion of explained variance of 69.56%. Finally, it is also noteworthy that the data obtained for the death anxiety variable, considering this bifactor model, is highly reliable for multidimensional scales (ω ≥ .80). Thus, the evidence indicates that the structure of three specific factors and one general factor is the most plausible. Moreover, it is consistent with the theory, is derived from the analysis methodology applied, and has practical utility, in that it would allow in the future to determine the greater weight of any of these three factors in the anxiety responses of the examinees.\n\nAs Table 1 shows, for the most part, the DAS items meet the parameters previously established to claim that the data matrix can be reduced to a smaller set of latent factors: magnitudes.\n\nFinally, Table 4 presents the results of the factorial invariance analysis as a function of sex and age. Along these lines, the magnitudes of the variations in CFI (ΔCFI < .010), RMSEA (ΔRMSEA < .015), and SRMR (ΔSRMR ≤ .030) were minimal. Thus, the empirical evidence shows that the study participants interpret the meaning of the DAS items in a very similar way and that the scores obtained in this test are only attributable to the presence of the latent variable death anxiety, without depending on the characteristics of the examinees. Therefore, the new version of the DAS measures death anxiety fairly, without bias, in the Peruvian adult population, regardless of gender or age.\n\n\n4. Discussion\n\nThis study is the first to examine the psychometric properties of the Death Anxiety Scale and to provide evidence of its usefulness as a measure of this variable in the general non-clinical population of Peru (n=1248). Studies with a clinical sample were only conducted in Trujillo,17 health personnel in Lima,18 Trujillo, older adults19 and older adults in Chimbote.20 All of them were in zones and had samples of less than 600 subjects. It should be noted that the reliability for internal consistency in health personnel reached .95, followed by older adults in Trujillo19 with .93. In contrast, in other countries such as Argentina16 in 859 adult subjects, it only reached a reliability of .80, and in Spain15 in a clinical sample, the value was .77.\n\nTo perform the CFA, three measurement models were tested to perform CFA, which is a good option when validating instruments with confirmatory factor analysis.51 Initially, a model of three correlated factors was tested, as proposed by Rivera-Ledesma (2009)12 in its Mexican version, as it is the version with the largest number of recent studies in Spanish. Subsequently, two hierarchical models were tested: a second-order formative model and another bifactor multidimensional model, in order to find empirical evidence in favor of the existence of a global score on the Death Anxiety Scale.\n\nConsequently, our results support the three-dimensional structure of the DAS, which in turn allows a global score, as reported in previous national18–20 and international studies,12 in Spain, four factors were found in a clinical sample,15 whereas in Argentina, in non-clinical adults, a better fit to a unifactorial structure was found. This indicates that the DAS, at least in the Peruvian context, can be used as a self-report instrument to measure death anxiety in the general nonclinical adult population.\n\nThe construct validity of the DAS was tested and found to be satisfactory based on the CFA, and all model fit indices were acceptable. The AFC showed that the model that best fits our data was the three-factor oblique correlated model for all the three dimensions. The three-factor oblique model was better than the one- and two-factor models, indicating that death anxiety has a total score as a variable and, in turn, is composed of three dimensions.\n\nWe chose to eliminate two items with poor factor loadings (factor loadings < 0.4) and weaker values than other items in the study sample, such as item 9 (“I am afraid of having a painful death”) of the fear of dying dimension. Likewise, Item 14 (“I am horrified to see a corpse”) of the dimension of fear of life coming to an end. Thus, the adequacy of the model is improved.\n\nThe internal consistency reliability results of the DAS showed excellent values for all dimensions, with a Cronbach’s alpha and McDonald’s Omega ≥ .80. These results confirmed previous reports on the reliability of DAS in different studies and populations.12–20\n\nIn the present study, the fairness of measurement between sexes and age was also examined using a factorial invariance analysis. It was found that the DAS exhibits complete configurational and metric invariance between sexes and ages. This indicates that DAS can be used to measure death anxiety with the same meaning for women and men or for Peruvian adult subjects of different non-clinical ages. That is, there were no differences in the structure of DAS between the sexes and age groups in the study sample. This result disagrees with the findings of Peñaloza et al.,19 who reported that scores differed between men and women.\n\nThe main contribution of this study is that it is the first time that DAS validation has been performed in the general Peruvian population, covering most regions of Peru. However, this study had some limitations. First, a cross-sectional and not longitudinal design was used, in which the reliability analysis was based on internal consistency and not on the test-retest stability measure. Second, although death anxiety was universal, Non-probability sampling could pose a limitation in generalizing the sample results to the population. Third, the use of this type of convenience sampling could cause selection bias since only subjects with access to social networks responded to the online questionnaire. Finally, given that the general population was included, another limitation was that the clinical population was not analyzed, which is an option for future studies.\n\n\nConclusions\n\nIn summary, our results show that the DAS has good psychometric properties for Peruvian adults. We found that DAS is valid and reliable, with the ability to clearly distinguish death anxiety from other factors. Our data suggest that this instrument is invariant between sexes and non-clinical age groups. Consequently, DAS can be used as a self-report instrument to detect death anxiety in the general adult Peruvian population. This will allow public policies, such as assistance programs, to identify subjects at higher risk and more vulnerable to developing mental health disorders related to quality of life that the state should guarantee.\n\nThis study is framed in the field of public and mental health, specifically constituting a methodological contribution that will overcome the lack of a useful, valid, and reliable instrument in the current Peruvian context, involving much more accurate and rigorous measurements of the variable in question, thus serving not only health professionals but also promoters and citizens themselves.\n\nAll of these factors contribute to the challenge of preventing and reducing the risk of mental diseases and achieving a biopsychosocial balance. This perspective is in line with the framework of the Global Goals of the 2030 Agenda for Sustainable Development, where Goal 3 aims to ensure healthy lives and promote well-being for all ages worldwide.\n\n\nConsent statement\n\nThe consent of the participants was given in writing before answering the online instruments.",
"appendix": "Data availability\n\nZenodo: De La Cruz-Valdiviano CB: Death anxiety scale (DAS) /database. Zenodo; 2023. doi: https://doi.org/10.5281/zenodo.10689053. 70\n\nThis project contains the following underlying data:\n\nDatabase (Statistical results after the application of the Death anxiety scale-DAS).xlsx\n\n• https://doi.org/10.5281/zenodo.10689053\n\n• https://datos.ucv.edu.pe/handle/20.500.14413/3\n\nZenodo: Death anxiety scale (DAS): internal structure and factorial invariance in Peruvian adults. Zenodo; 2024. https://doi.org/10.5281/zenodo.12191803. 71\n\nThis project contains the following extended data:\n\n• Final results (word).docx\n\n• Ethics Committee Approval.pdf (Etica UCV 70 De La Cruz Valdiviano)\n\n• Permission to use the Death Anxiety Scale_De la Cruz.\n\n• Informed consent\n\n• Death anxiety in Peruvian adults during the COVID-19 pandemic (Open Access).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nLimonero JT, Tomás-Sábado J, Fernández-Castro J, et al.: Competencia personal percibida y ansiedad ante la muerte en estudiantes de enfermería [Perceived personal competence and death anxiety in nursing students]. Ansiedad y estrés. 2010; 16(2): 177–188. Reference Source\n\nTomás-Sábado JT, Gómez-Benito J: Variables relacionadas con la ansiedad ante la muerte [Variables related to death anxiety]. Rev Psicol Gen Apl. 2003; 56(3): 257–279. 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Publisher Full Text\n\nRequejo Chapilliquén M, Sánchez Carbajal D: Ajuste mental y ansiedad ante la muerte en pacientes con cáncer terminal [neuroscience Mental Adjustment and Death Anxiety in Terminal Cancer Patients. neuroscience]. J Neuro and Pub Health. 2021; 1(2): 53–61. Publisher Full Text Reference Source\n\nPeñaloza S: Propiedades psicométricas de la Escala de Ansiedad ante la Muerte (DAS) de Templer, en personal de salud, Lima Metropolitana- 2021 [ Psychometric Properties of Templer’s Death Anxiety Scale (DAS) in health care personnel, Lima Metropolitana- 2021]. Licentiate thesis in Psychology, Universidad César Vallejo; Lima-Norte, Peru, February 2022.Reference Source\n\nGrauss MK: Propiedades Psicométricas de la Escala de Ansiedad ante la Muerte en pacientes adulto mayor de Instituciones de la Ciudad de Trujillo [Psychometric properties of the Death Anxiety Scale in elderly patients from institutions in the city of Trujillo]. Licentiate thesis in Psychology, Universidad César Vallejo; Trujillo, Peru, September 2016.Reference Source\n\nRodriguez JE: Propiedades Psicométricas de la Escala de Ansiedad ante la Muerte en adultos mayores de Chimbote [Psychometric Properties of the Death Anxiety Scale in Chimbote’s older adults]. Licentiate thesis in Psychology, Universidad César Vallejo; Chimbote, Peru, February 2020.Reference Source\n\nRAE Diccionario de la Real Academia Española: Ansiedad [Anxiety]. (accessed on 1 Juanary 2023). Reference Source\n\nLimonero J: Evaluación de aspectos perceptivos y emocionales en la proximidad de la muerte [Assessment of perceptual and emotional aspects in the proximity of death]. Doctoral thesis, Universitat Autònoma de Barcelona; España.1994. Reference Source\n\nHamilton MC: Diagnosis and rating of anxiety. Br J Psychiatry. 1969; 3: 76–79.\n\nEysenck HJ: A theory of the incubation of anxiety/fear responses. Behav. Res. Ther. 1968; 6(3): 309–321. 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The Reviewer’s Guide to Quantitative Methods in the Social Sciences. 2nd ed.New York: Routledge; 2018; pp. 98–122.\n\nMuthén B, Kaplan D: A comparison of some methodologies for the factor analysis of non-normal Likert variables. Br J Math Stat Psychol. 1985; 38(2): 171–189. Publisher Full Text\n\nKline PA: Handbook of test construction: Introduction to psychometric design. 1a ed.London, England: Routledge; 2016.\n\nWilliams B, Onsman A, Brown T: Exploratory factor analysis: A five-step guide for novices. Australas J Paramed. 2010; 8(3): 1–13. Publisher Full Text Reference Source\n\nFerrando PJ, Anguiano-Carrasco C: El análisis factorial como técnica de investigación en psicología [Factor analysis as a research technique in psychology]. Pap Psicól. 2010; 31(1): 18–33.\n\nTabachnick BG, Fidell LS: Using multivariate statistics. 7a ed.Upper Saddle River, NJ: Pearson; 2018.\n\nLüdecke D, Ben-Shachar M, Patil I, et al.: Extracting, computing and exploring the parameters of statistical models using R. J Open Source Softw. 2020; 5(53): 24–45. Publisher Full Text\n\nLópez-Aguado M, Gutiérrez-Provecho L: Cómo realizar e interpretar un análisis factorial exploratorio utilizando SPSS [How to perform and interpret an exploratory factor analysis using SPSS]. REIRE Rev Innov Recer Educ. 2019; 12 (2)(2): 1–14. Publisher Full Text\n\nLloret-Segura S, Ferreres-Traver A, Hernández-Baeza A, et al.: El análisis factorial exploratorio de los ítems: una guía práctica, revisada y actualizada. [Exploratory factor analysis of items: a practical guide, revised and updated]. An Psicól. 2014; 30(3): 51–69. 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Publisher Full Text\n\nDominguez Lara SA: Análisis psicométrico de la escala de bienestar psicológico para adultos en estudiantes universitarios de Lima: un enfoque de ecuaciones estructurales [Psychometric analysis of the psychological well-being scale for adults in university students in Lima: a structural equation approach]. Psychol. 2014; 8(1): 23–31. Publisher Full Text Reference Source\n\nBrown TA: Confirmatory factor analysis for applied research. second edition. 2nd. edic.New York, NY: Guilford Publications; 2014. Reference Source\n\nDiStefano C, Morgan GB: A comparison of diagonal weighted least squares robust estimation techniques for ordinal data. Struct Equ Modeling. 2014; 21(3): 425–438. Publisher Full Text\n\nHerrero J: El Análisis Factorial Confirmatorio en el estudio de la Estructura y Estabilidad de los Instrumentos de Evaluación: Un ejemplo con el Cuestionario de Autoestima CA-14 [Confirmatory Factor Analysis in the Study of the Structure and Stability of Assessment Instruments: An Example with the Self-Esteem Questionnaire CA-14]. Interv Psicosoc. 2010; 19(3): 289–300. Publisher Full Text Reference Source\n\nHair JF, Black WC, Babin BJ, et al.: Multivariate data analysis. 8th edic.Boston: Cengage; 2019.\n\nMarôco J: Análise de Equações Estruturais: fundamentos teóricos, software & aplicações [Structural Equation Analysis: theoretical foundations, software & applications]. 2nd. edic.ReportNumber; 2014.\n\nSchmid J, Leiman JM: The development of hierarchical factor solutions. Psychometrika. 1957; 22(1): 53–61. Publisher Full Text\n\nWolff HG, Preising K: Exploring item and higher order factor structure with the Schmid-Leiman solution: syntax codes for SPSS and SAS. Behav Res Methods. 2005; 37(1): 48–58. PubMed Abstract | Publisher Full Text\n\nSteiner M, Grieder S: EFAtools: An R package with fast and flexible implementations of exploratory factor analysis tools. J Open Source Softw. 2020; 5(53): 2521. Publisher Full Text\n\nReise SP, Scheines R, Widaman KF, et al.: Multidimensionality and structural coefficient bias in structural equation modeling: A bifactor perspective. Educ Psychol Meas. 2013; 73(1): 5–26. Publisher Full Text\n\nSmits IA, Timmerman ME, Barelds DP, et al.: The Dutch symptom checklist-90-revised. Eur J Psychol Asess Assessment. 2014; 31(4): 263–271. Publisher Full Text\n\nHancock GR, Mueller RO: Rethinking construct reliability within latent variable systems.Cudeck R, du Toit S , Sörbom D, editors. Structural equation modeling: Present and future—A Festschrift in honor of Karl Jöreskog. Scirp.org; 2001; pp. 195–216. Reference Source\n\nMcDonald RP: Test theory: A unified treatment. 1st ed.London, England: Psychology Press; 2013. Publisher Full Text\n\nDunn TJ, Baguley T, Brunsden V: From alph t omega: A practical solution to the perva-sive problem of internal consistency estimation. Br J Psychol. 2013; 105(3): 399–412. PubMed Abstract | Publisher Full Text\n\nRodriguez A, Reise SP: Haviland MG Applying bifactor statistical indices in the evaluation of psychological measures. J Pers Assess. 2015; 98(3): 223–237. PubMed Abstract | Publisher Full Text\n\nNunnally JC: An overview of psychological measurement. Clinical diagnosis of mental disorders: A handbook.1978; 97–146.\n\nByrne BM: Testing for multigroup equivalence of a measuring instrument: a walk through the process. Psicothema. 2008; 20(4): 872–882. PubMed Abstract Reference Source\n\nJorgensen TD: How to estimate absolute-error components in structural equation models of generalizability theory. Psych. 2021; 3(2): 113–133. Publisher Full Text Reference Source\n\nChen FF: Sensitivity of goodness of fit indexes to lack of measurement invariance. Struct Equ Modeling. 2007; 14(3): 464–504. Publisher Full Text Reference Source\n\nCheung GW, Rensvold RB: Evaluating goodness-of-fit indexes for testing measurement invariance. Struct Equ Modeling. 2002; 9(2): 233–255. Publisher Full Text\n\nHirschfeld G, Von Brachel R: Improving Multiple-Group confirmatory factor analysis in R–A tutorial in measurement invariance with continuous and ordinal indicators. Pract Assess Res Eval. 2014; 19(1): 7. Reference Source\n\nDimitrov DM: Testing for factorial invariance in the context of construct validation. Meas Eval Couns Dev. 2010; 43(2): 121–149. Publisher Full Text\n\nDe La Cruz-Valdiviano CB: Death anxiety scale (DAS) /database. Zenodo. 2023. Publisher Full Text\n\nDe La Cruz-Valdiviano CB: Death anxiety scale (DAS): internal structure and factorial invariance in Peruvian adults. [Data set]. Publisher Full Text"
}
|
[
{
"id": "304672",
"date": "12 Aug 2024",
"name": "Afreen Faiza",
"expertise": [
"Reviewer Expertise Psychometrics",
"thanatology",
"theology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. Literature Review Section could include recent findings related to death anxiety and its components focused on death anxiety in context of general population as the sample target for scale validation seems general population rather than terminal or physically ill or preoccupation about death. 2. Do Studies cited in : Section 1.1 Rivera and Montero12 Peñaloza18 used Templar DAs?? if yes please state. 3. do we really need to write separately about anxiety and make another section 1.2 ? better link it with death anxiety or write description about how fear is different from anxiety. 4. what was religious backgrounds/ health status of participants,\n\n5. major concern is that how templer DAS divided into 3 factors ?? what was your rationale to do so as it has one pf major drawback was that TDAs is uni dimensional scale. how we come up with different names of sub scales : Fear of agony or pathology, Fear of life coming to an end, Fear of death, ( what subscales measures, and how it comply with theory of Templer scale )\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12849",
"date": "22 Nov 2024",
"name": "Carlos De La Cruz-Valdiviano",
"role": "Author Response",
"response": "Literature Review Section could include recent findings related to death anxiety and its components focused on death anxiety in context of general population as the sample target for scale validation seems general population rather than terminal or physically ill or preoccupation about death. Response: In the literature review, the initial focus was on research concerning death anxiety in clinical populations due to the influence these studies have had on the validation of the Death Anxiety Scale (DAS). However, we understand the importance of providing a more updated and relevant framework for the general population, as the sample in this study consists of Peruvian adults without severe medical conditions. To strengthen the literature review section, we have consulted recent studies addressing death anxiety in the general population, and I include below some relevant findings that will be integrated into the manuscript: Influence of Sociocultural Factors: Recent research has indicated that death anxiety is strongly influenced by sociocultural and contextual factors72. These studies emphasize that death anxiety can vary significantly between countries and cultures, depending on elements such as religious beliefs, social norms, and exposure to conflict contexts. This aspect is particularly relevant for the Peruvian population, given the cultural diversity and sociocultural values that could influence levels of death anxiety. Death Anxiety in Young and Middle-Aged Adults: Studies such as those by Abdel-Khalek and Neimeyer73 have demonstrated that death anxiety is not exclusive to clinical populations or older adults. High levels of death anxiety have been observed in young and middle-aged adults, who face uncertainties common to this stage of life, such as changes in family and professional roles. These findings are crucial for the context of our Peruvian sample, as most participants fall within a similar age range. Gender Differences: Some recent studies have suggested that there are significant gender differences in the manifestation of death anxiety in the general population 73. Women tend to report higher levels of death anxiety than men, which could be attributed to a greater predisposition to experiencing emotional concerns. This aspect will be included in the review to provide better contextualization of the study's target population. Relationship between Death Anxiety and Psychological Well-Being: Lastly, recent studies have explored the relationship between death anxiety and psychological well-being in the general population. According to Abdel-Khalek and Neimeyer 73, death anxiety is inversely related to subjective well-being, indicating that elevated levels of death anxiety are associated with a decrease in quality of life. This finding is particularly relevant to emphasize the importance of adequately measuring death anxiety in the general population and considering its implications for mental well-being. We once again appreciate your exhaustive review and your suggestions, which will undoubtedly enrich the scope and depth of the analysis of this study. However, we believe that framing the research in the context of the pandemic justifies studying death anxiety in the general population. 2. Do Studies cited in : Section 1.1 Rivera and Montero12 Peñaloza18 used Templar DAs?? if yes please state Response: Yes, both cited studies used Templer's Death Anxiety Scale (DAS) as an instrument to assess death anxiety in their respective samples. Specifically, the study by Rivera and Montero evaluated the psychometric properties of the DAS in a sample of Mexican subjects, while Peñaloza's study also used Templer's DAS to examine its psychometric properties in a sample of healthcare personnel from Lima Metropolitan. 3. Do we really need to write separately about anxiety and make another section 1.2 ? better link it with death anxiety or write description about how fear is different from anxiety. Response: We understand the reviewer's concern regarding the separation of the sections related to anxiety and death anxiety. However, we believe that the way these sections were organized has solid theoretical and methodological support, which also reflects a logical and appropriate structure for the reader's understanding. First, in the section on anxiety (1.2), the intention was to provide a conceptual framework necessary to understand anxiety from a general perspective. Anxiety is a central component in analyzing death anxiety, but each has specific characteristics that needed to be explained independently to avoid confusing the reader. Anxiety is a state of general arousal that can manifest in different contexts and be influenced by various factors, such as existential fear and the perception of the threat of death 74. Separating these concepts allowed us to clarify the distinction between anxiety as a broad phenomenon and death-related anxiety, thereby adhering to an academic rigor criterion that facilitates a comprehensive understanding of the construct of death anxiety. Second, the inclusion of a section discussing general anxiety is also justified from the perspective of Terror Management Theory (TMT), as presented by Zuccala et al.75. This theory proposes that death anxiety is a specific form of anxiety underlying various mental disorders, and its correct understanding begins by defining anxiety as a general response to the perception of existential threats. This approach allowed us to develop a solid conceptualization of how fear of death is linked to other fears and anxieties, and laid the foundation for the clear differentiation between fear and anxiety described later. Third, the structure chosen for the manuscript also responds to methodological coherence, as the factorial solutions found in the exploratory and confirmatory analysis revealed three distinct dimensions in Templer's Death Anxiety Scale (DAS). Each of these dimensions is linked to specific components of anxiety that, according to studies such as those by Sharif Nia et al. 74, differ significantly in different cultural and sociodemographic contexts. The presence of multiple factors suggests that death anxiety is not merely a unidimensional fear but can be expressed in different forms, which justifies the proposed structure. Finally, we consider that the preprint publication of the manuscript already reflects a consensus on the organization of the sections and the methodological decisions made, which have already been reviewed and accepted (100%) by one of the peers. The need to discuss anxiety in general terms before addressing death anxiety is also a response to previous studies that emphasize the importance of contextualizing and clearly defining these concepts to ensure a precise understanding of the construct 75. For these reasons, we believe that it is not necessary to make modifications to the manuscript's structure. The current organization allows for a better understanding of the relationship between anxiety and death anxiety, meeting criteria for clarity and methodological rigor that are essential in this type of study. 4. what was religious backgrounds/ health status of participants? Response: Regarding the religious backgrounds of the participants, we acknowledge that this information represents one of the limitations of the present study. Detailed data on religious affiliation or the degree of religious involvement of the participants were not collected. It is important to mention that this aspect may have influenced the interpretation and response of participants to the Death Anxiety Scale (DAS), as religion can act as a modulatory mechanism of the fear of death. Consequently, this limitation is highlighted in the discussion of the study, and we suggest that future research include a thorough analysis of the impact of religious backgrounds to gain a deeper understanding of the phenomenon of death anxiety. Concerning health status, the study focused on the history of COVID-19, given the relevance of the pandemic to the experience of death anxiety in the general population. Specific data were collected on whether participants had contracted the disease, and the results showed that 45% of respondents reported having had COVID-19. This variable was considered due to the known impact of the pandemic on perceptions of vulnerability and the increase in existential anxiety in many people. However, other aspects of general health, such as the presence of chronic or terminal illnesses, were not addressed, which also constitutes a limitation of this study. This information will be included more clearly in the discussion to indicate how these limitations may have influenced the results obtained and how they should be addressed in future research. I once again appreciate your careful review and suggestions, which undoubtedly enrich the scope and depth of this study's analysis. Nevertheless, I believe that framing the research within the context of the pandemic justifies studying death anxiety in the general population. 5. Major concern is that how templer DAS divided into 3 factors ?? what was your rationale to do so as it has one pf major drawback was that TDAs is uni dimensional scale. how we come up with different names of sub scales : Fear of agony or pathology, Fear of life coming to an end, Fear of death, ( what subscales measures, and how it comply with theory of Templer scale?) Response: Justification of the Factor Structure In our study, the Death Anxiety Scale (DAS) was subjected to exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), revealing a structure of three interrelated factors, which contradicts the traditionally unidimensional nature attributed to the scale. These three emerging factors were named: Fear of agony or pathology, Fear of life ending, and Fear of death. The results indicated an accumulated variance of 53.3%, which supports the existence of additional components beyond the general factor of death anxiety. Naming the Subscales Fear of agony or pathology: This factor includes items that reflect concern about physical suffering or pain associated with death. The naming is derived from the qualitative analysis of the content of the items that make up this factor, which focus on aspects of distress over a painful death or prolonged illness. These findings are consistent with previous findings by Rivera and Montero, as well as Peñaloza, who also found that fear of the process of agony is a crucial component in the structure of death anxiety. Fear of life ending: This factor represents existential fear related to the perception of the end of life as an inevitable process. The items associated with this component suggest a concern for the finite nature of life and the uncertainty that comes with it, clearly distinguishing it from physical fear or the consequences of death. This type of fear has also been documented in cross-cultural studies where differences are observed in how the end of life is perceived and feared depending on the cultural context and sample evaluated 74. Fear of death: This factor groups items that address the fear of the idea of death itself, including the fear of the unknown that death represents. This component relates to abstract or philosophical anxiety about the act of dying, which is consistent with studies that have evidenced a distinct psychological component in death anxiety 75. In the cross-cultural analysis by Sharif Nia et al. 74, it was observed that the factor structure of the DAS varied significantly across different cultural contexts, highlighting the need to adapt the scale according to the specific characteristics of each population. Coherence with Templer's Theory Although Templer's Scale was initially conceived as unidimensional, recent studies have suggested the existence of multiple dimensions depending on the cultural and population context in which it is applied. For instance, the systematic review conducted by Sharif Nia et al. 74 found factor structures ranging from two to five factors, depending on the cultural context and evaluated population. This evidence supports the need to reconsider the unidimensionality of the scale in specific contexts like the Peruvian one, in which we identified three factors that seem to capture particular nuances of death anxiety. Zuccala et al. 75 also point out that variability in the DAS factor structure can be attributed to cultural differences and the translation of the instrument's content. Indeed, death anxiety tends to manifest differently according to the cultural context, directly affecting the scale's validity and reliability. Therefore, it has been recommended to conduct continuous evaluations and specific cultural adaptations before applying it in clinical and multicultural settings. Empirical Evidence In the confirmatory factor analysis (CFA), the bifactor model best fit the data, with adequate fit indices (CFI ≥ .94, TLI ≥ .94, SRMR ≤ .08, RMSEA ≤ .07) and a proportion of explained variance of 69.56%. This suggests that while a general factor measuring death anxiety exists, the three specific dimensions have sufficient independence to be considered validated subscales, providing greater precision in the evaluation of death anxiety. This is consistent with the results of the exploratory factor analysis previously mentioned. Conclusion The division of the Death Anxiety Scale into three factors is based on rigorous empirical analysis that reflects the underlying structure of the data and is in line with previous cross-cultural studies that have identified multidimensional structures. This conceptualization allows for a more comprehensive and nuanced assessment of death anxiety in the Peruvian population, capturing specific aspects that may not be evident in a unidimensional structure. The results of Sharif Nia et al. 74 and Zuccala et al. 75 support the need to adapt the DAS scale according to the cultural and sociodemographic particularities of each sample, which motivated us to validate a three-dimensional structure in the Peruvian context to provide a more sensitive and accurate assessment tool for our target population."
}
]
},
{
"id": "328813",
"date": "22 Oct 2024",
"name": "Hanaa Shuwiekh",
"expertise": [],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGood research in its methodological treatment, although the concept, which is death anxiety, has been studied a lot. Good luck.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-801
|
https://f1000research.com/articles/12-755/v1
|
27 Jun 23
|
{
"type": "Software Tool Article",
"title": "RBP-Tar – a searchable database for experimental RBP binding sites",
"authors": [
"Katarina Gresova",
"Tomas Racek",
"Vlastimil Martinek",
"David Cechak",
"Radka Svobodova",
"Panagiotis Alexiou",
"Katarina Gresova",
"Tomas Racek",
"Vlastimil Martinek",
"David Cechak",
"Radka Svobodova"
],
"abstract": "Background: RNA-binding proteins (RBPs) play a critical role in regulating gene expression by binding to specific sites on RNA molecules. Identifying these binding sites is crucial for understanding the many functions of RBPs in cellular function, development and disease. Current experimental methods for identifying RBP binding sites, such as ultra-violet (UV) crosslinking and immunoprecipitation (CLIP), and especially the enhanced CLIP (eCLIP) protocol, were developed to identify authentic RBP binding sites experimentally. Methods: To make this data more accessible to the scientific community, we have developed RBP-Tar (https://ncbr.muni.cz/RBP-Tar), a web server and database that utilises eCLIP data for 167 RBPs mapped on the human genome. The web server allows researchers to easily search and retrieve binding site information by genomic location and RBP name. Use case: Researchers can produce lists of all known RBP binding sites on a gene of interest, or produce lists of binding sites for one RBP on different genomic loci. Conclusions: Our future goal is to continue to populate the web server with additional experimental datasets from CLIP experiments as they become available and processed, making it an increasingly valuable resource for the scientific community.",
"keywords": [
"RNA Binding Proteins",
"CLIP",
"RBP",
"Web-server"
],
"content": "Introduction\n\nRNA binding proteins (RBPs) are key players in a broad spectrum of RNA regulation, including all stages of the RNA lifecycle (Gerstberger et al. 2014; Gebauer et al. 2021). Eukaryotic genomes typically encode hundreds of RBPs. For example, over 1500 human RBPs involved in the maturation, transport, stability and translation of coding and non-coding RNA were recently characterised and manually curated (Gerstberger et al. 2014). Each RBP can typically target hundreds of RNAs in a complex coordinated fashion (Hogan et al. 2008). The general transcriptomic locations of thousands of RNA binding sites corresponding to hundreds of RBPs have been identified using a family of experimental techniques based on RBP CrossLinking, ImmunoPrecipitation and Sequencing (CLIP-Seq) (Chi et al. 2009; Licatalosi et al. 2008; Moore et al. 2014; Hafner et al. 2010). A thorough exploration of tens of RBPs binding characteristics in vitro has shown that RBPs can differentiate their binding sites with context preferences beyond narrowly defined binding sequence motif and secondary structure often involving complex binding configurations (Dominguez et al. 2018). Among the experimental techniques available to date, the enhanced CLIP (eCLIP) protocol (Van Nostrand et al. 2016) is particularly important, as it significantly reduces required amplification and increases specificity in identifying authentic binding sites. This improves the efficiency and accuracy of RBP binding site identification and allows for a deeper understanding of the role of RBPs in gene regulation.\n\nThe availability of a large amount of data points produced from the same experimental technique can be very beneficial for applications such as machine learning, as it allows researchers to train and test models with more confidence. Here we present RBP-Tar (Tomáš Raček 2023), a centralised and searchable database of experimentally identified RBP binding sites that can significantly facilitate the study of the RBP mediated gene regulation. Using RBP-Tar, researchers can quickly and cleanly retrieve RBP binding sites constrained by both genomic location and associated RBP for hundreds of RBPs.\n\n\nMethods\n\nPipeline for reproducible data download and annotation\n\nWe have developed a reproducible and easy-to-use pipeline for downloading and annotating RBP eCLIP data from the ENCODE (Luo et al. 2020) database.\n\nMetadata for eCLIP experiments, as well as additional files containing genomic coordinates are downloaded from the ENCODE database with the following parameters:\n\n“status= released&\n\ninternal_tags=ENCORE&\n\nassay_title=eCLIP&\n\nbiosample_ontology.term_name=K562&\n\nbiosample_ontology.term_name=HepG2&\n\nfiles.file_type=bed+narrowPeak&\n\ntype=Experiment”.\n\nFollowing the download, information about the chromosome, start position, end position and strand of reads are extracted for each RBP binding site. Binding sites are filtered by length, excluding ones shorter than 20 and longer than 100 nucleotides. As a last step, genomic sequences of binding sites are retrieved.\n\nThe described pipeline is implemented as a set of python scripts and is freely available at GitHub.\n\nUsing this pipeline, data for 167 RBPs on two cell lines (K562, HepG2) were downloaded. In total, 1.8 Gb of data, representing more than 25 million binding sites, were thus processed.\n\nWeb server\n\nHere we present RBP-Tar, a web server that can access the above curated dataset of RBP binding sites (https://ncbr.muni.cz/RBP-Tar) and was built with Python (RRID:SCR_008394), the web development framework Flask, and a simple SQLite database (RRID:SCR_017672). The application’s source codes can be found on the project’s GitHub page, along with the requirements and instructions for the deployment if a user wants to run the application locally.\n\nThe web user interface allows searching and filtering based on the start and end position of the binding site, strand, chromosome, and protein name. It offers the download of the filtered data based on the search done by the user. Due to the size of the dataset, the view is limited to 10 000 results. However, the whole dataset can be conveniently downloaded as a gzipped CSV (579 MB) (here).\n\nThe RBP-Tar web server can take as input any of the following user-provided parameters: [Start min, Start max] denote the limits of the low genomic coordinate of the locus of interest. Similarly, [End min, End max] denote the limits of the high coordinate. [Strand] and [Chromosome] can be used to narrow down the search to only one strand and a specific chromosome. Using these combinations of parameters, a user can easily search for binding sites on their favourite gene, exon, or even a whole chromosome. The last parameter is [Protein name], which brings out a drop-down menu of all the RBPs in the database. If this parameter is not set, all RBPs are queried.\n\nResults are shown as a table with the [Chromosome, Start, End, Strand] genomic location of the binding site, followed by the [Protein name] of the associated RBP and the [Sequence] of the binding site contains the genomic sequence of the binding site. Results can be seen online in a table format or downloaded as a CSV file with one button click. We expect most users to download the results and use them for further downstream analyses.\n\n\nUse cases\n\nThe first and potentially most common use case would be the query of all known RBP binding sites on a gene of interest. For example, we can query our web server with the coordinates of the Fused in Sarcoma (FUS) gene (chr16: 31180139-31191605, +) and leave the protein field empty. After this search, all 5 045 known RBP binding sites on this gene are returned and can be easily downloaded in a CSV file for further analysis (Figure 1).\n\nIn fact, the gene we used encodes the RBP FUS, which plays important roles, among others, in neurodegeneration and cancer progression. We can use the filter [Protein Name] to identify the potential self-targeting of FUS on itself. Indeed, we can thus identify 72 potential FUS self-targeting binding sites identified via eCLIP (Grešová & Raček 2023) (Figure 2). Of course, the biological relevance of this type of finding is left to the users, as is the further validation of high-throughput derived RBP binding sites.\n\nA potential user may want to develop an RBP binding site machine learning tool that would be able to predict binding sites based on a sequence. It is important to make sure that training and testing sets for their machine learning method are not overlapping. Using our web server, they can download all binding sites for a specific RBP, for example, on chromosome 1, and use them as a training set (Figure 3). Then do the same for chromosome 2 and use it as an independent testing set, thus ensuring that training and testing set do not overlap.\n\n\nConclusion\n\nRecent advancements in experimental techniques, such as eCLIP, have greatly expanded our understanding of RBP binding preferences and their role in gene regulation. The development of centralised and searchable databases of experimentally identified RBP binding sites allows researchers to access and analyse the binding preferences of RBPs easily. This information can be used to identify known binding sites on genes of interest and aid in training machine-learning models for RBP binding site prediction. This paper presents RBP-Tar, a centralised web server that can retrieve RBP Target sites with location and RBP constraints. RBP-Tar has been designed to be easily accessible by non-experts. It is still confined to a single source of data, which is helpful for avoiding experimental design effects, but makes its scope limited. We plan to expand the web server with other sources of data, as well as ways for the user to be able to take into account provenance and experimental variation.",
"appendix": "Data availability\n\nAll data used in RBP-Tar has been downloaded from ENCODE and Ensembl projects in April 2022. RBP eCLIP metadata were downloaded from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type= bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true. List of all downloaded files containing genomic coordinates can be found here: [https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt] (hundreds of filenames). Reference genome was downloaded from http://ftp.ensembl.org/pub/release-97/fasta/homo_sapiens/dna/Homo_sapiens.GRCh38.dna.toplevel.fa.gz\n\nColumns ‘chrom’, ‘chromStart’, ‘chromEnd’ and ‘strand’ from downloaded files containing genomic coordinates can be found here: https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/tree/main/csv. The whole dataset (curated and including sequence) can be downloaded from https://rbp-tar.ncbr.muni.cz/ as a gzipped CSV (579 MB) (https://rbp-tar.ncbr.muni.cz/download_all).\n\n\nReferences\n\nChi SW, Zang JB, Mele A, et al.: Argonaute HITS-CLIP Decodes microRNA–mRNA Interaction Maps. Nature. 2009; 460: 479–486. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDominguez D, Freese P, Alexis MS, et al.: Sequence, Structure, and Context Preferences of Human RNA Binding Proteins. Mol. Cell 2018; 70(5): 854–67.e9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGerstberger S, Hafner M, Tuschl T: A Census of Human RNA-Binding Proteins. Nat. Rev. Genet. 2014; 15(12): 829–845. PubMed Abstract | Publisher Full Text\n\nGebauer F, Schwarzl T, Valcárcel J, et al.: A-binding proteins in human genetic disease. Nat. Rev. Genet. 2021; 22: 185–198. Publisher Full Text\n\nGrešová K, Raček T: ML-Bioinfo-CEITEC/rbp_encode_eclip: Publication without data (v1.0.1). [Software]. Zenodo. 2023. Publisher Full Text\n\nHafner M, Landthaler M, Burger L, et al.: Transcriptome-Wide Identification of RNA-Binding Protein and microRNA Target Sites by PAR-CLIP. Cell. 2010; 141(1): 129–141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHogan DJ, Riordan DP, Gerber AP, et al.: Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System. PLoS Biol. 2008; 6(10): e255. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLicatalosi DD, Mele A, Fak JJ, et al.: HITS-CLIP Yields Genome-Wide Insights into Brain Alternative RNA Processing. Nature 2008; 456(7221): 464–469. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuo Y, Hitz BC, Gabdank I, et al.: New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res. 2020 Jan 8; 48(D1): D882–D889. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoore MJ, Zhang C, Gantman EC, et al.: Mapping Argonaute and Conventional RNA-Binding Protein Interactions with RNA at Single-Nucleotide Resolution Using HITS-CLIP and CIMS Analysis. Nat. Protoc. 2014; 9(2): 263–293. Publisher Full Text\n\nNostrand V, Eric L, Pratt GA, et al.: Robust Transcriptome-Wide Discovery of RNA-Binding Protein Binding Sites with Enhanced CLIP (eCLIP). Nat. Methods 2016; 13(6): 508–514. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRaček T: RBP-Tar (v1.0.0). [Software]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "224199",
"date": "18 Dec 2023",
"name": "Xiaoyong Pan",
"expertise": [
"Reviewer Expertise The authors need solve some issues before published"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt. In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE (https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly",
"responses": [
{
"c_id": "12001",
"date": "12 Aug 2024",
"name": "Panagiotis Alexiou",
"role": "Author Response",
"response": "Reviewer Comment: In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt. In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE (https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists."
}
]
},
{
"id": "224195",
"date": "18 Dec 2023",
"name": "Clifford A Meyer",
"expertise": [
"Reviewer Expertise Epigenetics",
"Chromatin analysis",
"Gene regulation",
"Single cell"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval.\nThe scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones.\nIt appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked.\n\nAs processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO.\nThe search features are useful, although it is hard to interpret the results. Some ranking of the results from most significant to least is needed. It would also be helpful to enable filtering based on some binding sites statistics.\nOverall, the resource is limited in terms of the data included and the website features. It would be helpful to include quality control metrics to let users know which samples are more informative.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "12002",
"date": "12 Jul 2024",
"name": "Panagiotis Alexiou",
"role": "Author Response",
"response": "This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries (https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf. This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position."
}
]
}
] | 1
|
https://f1000research.com/articles/12-755
|
https://f1000research.com/articles/12-1252/v1
|
29 Sep 23
|
{
"type": "Systematic Review",
"title": "Reporting of angiographic studies in patients diagnosed with a cerebral arteriovenous malformation: a systematic review",
"authors": [
"Suparna Das",
"Paul Kasher",
"Mueez Waqar",
"Adrian Parry-Jones",
"Hiren Patel",
"Paul Kasher",
"Mueez Waqar",
"Adrian Parry-Jones",
"Hiren Patel"
],
"abstract": "A cerebral arteriovenous malformation (cAVM) is an abnormal tangle of cerebral blood vessels. The consensus document by the Joint Writing Group (JWG)\nhighlighted which cAVM features should be recorded. Subsequent publications have reported cAVM angioarchitecture, but it is unknown if all followed the JWG recommendations.\nThe aim of this systematic review was to describe use of the JWG guidelines.\nA database search, using the PRISMA checklist, was performed. We describe the proportion of publications that used JWG reporting standards, which standards were used, whether the definitions used differed from the JWG, or if any additional angiographic features were reported.\nOut of 4306 articles identified, 105 were selected, and a further 114 from other sources. Thirty-three studies (33/219; 15%) specifically referred to using JWG standards.\nSince the JWG publication, few studies have used their standards to report cAVMs. This implies that the angioarchitecture of cAVMs are not routinely fully described.",
"keywords": [
"cerebral arteriovenous malformation",
"angioarchitecture",
"reporting",
"consensus"
],
"content": "Introduction\n\nCerebral arteriovenous malformations (cAVMs) cause death and disability mostly in the young.1 The fact that cAVM treatment is associated with significant morbidity and mortality poses additional challenges. Treatment is currently aimed at shrinking or excising the lesion, usually after it has ruptured or caused symptoms. Management decisions require a case-by-case multidisciplinary discussion balancing risks and benefits: there is no definitive algorithm for management.\n\nTypically, digital subtraction angiography (DSA) is used to classify cAVMs, which have a complex morphology with each malformation being unique. This makes reliably classifying cAVMs challenging for clinicians managing them. Although reliability studies have shown good intra-observer agreement on the characterisation of cAVM angioarchitecture, inter-observer agreement was poor.2\n\nTo address this, a consensus document was published by the Joint Working Group (JWG) of the Technology Assessment Committee: this provides elementary and clear definitions of terms and recommends which clinical and radiological cAVM features should be described and recorded (Table 1).3 This group, consisting of neuroradiologists, neurosurgeons, stroke and interventional neurologists practising in the United States of America, was created to produce guidelines for cAVM research.\n\nThe aim of this study was to systematically review the cAVM angioarchitecture literature to describe whether and how the JWG criteria were used.\n\n\nMethods\n\nThe review protocol was sent for registration to PROSPERO but not accepted due to “a perceived lack of direct impact on patient outcomes”. Reporting was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist.4\n\nPeer-reviewed publications were searched from 1 Jan 2001 (when JWG standards were published) and limited to human subjects and the English language. There was no restriction on age or sex. Studies were excluded if they were reviews and/or exclusively discussed cavernous malformations, dural arteriovenous fistula, angioma, capillary telangiectasia, Vein of Galen Malformations or other angiographically occult vascular malformations.\n\nA database search was performed using EMBASE and Medline, on 15/07/19 by one reviewing author (SD). It was repeated on 10/9/20 to update the search by a second author (MW). There was independent assessment by a librarian and another reviewing author (HP). In addition to the electronic searches, we conducted citation tracking, checked the reference lists, and reviewed the list of similar articles.\n\nTo conduct searches of the Medline electronic bibliographic database, combinations of the following search terms were used.\n\nMedical Subheadings: (Arteriovenous Malformations OR Arteriovenous Malformations, Intracranial) AND (Brain OR Intracranial)) AND (angioarchitecture OR angiogram OR angiographic OR aneurysm OR venous OR ectasia OR nidus OR angiogenesis OR varix).\n\nText Words: (Arteriovenous Malformations OR Arteriovenous Malformations, Intracranial) AND (Brain OR Intracranial)) AND (angioarchitecture OR angiogram OR angiographic OR aneurysm OR venous OR ectasia OR nidus).\n\nStudies were selected if they included any of the search strategy’s features: titles and abstracts were reviewed. Figure 1 demonstrates how articles were excluded.\n\nData extraction was performed by two independent reviewers (SD and HP) using the studies’ full text versions and by reviewing inclusion and exclusion criteria. Any disagreements were discussed between the two reviewers and an agreement reached. Pre-designed and piloted proforma were used.\n\nAll the individual data items collected from each paper are listed in Table 1.\n\n\n\n• Location\n\n\n\n• n/a\n\n\n\n• Size\n\n\n\n• recorded from MRI and angiography, measured in 3 dimensions (including cAVM’s largest diameter), volume calculated with ABC/2 formula\n\n\n\n• Eloquence\n\n\n\n• as per SMG score\n\n\n\n• Border\n\n\n\n• islands of normal cerebral parenchyma within cAVM nidus vs clearly outlined border with neighbouring parenchyma\n\n\n\n• superficial vs deep\n\n\n\n• Superficial: all cAVM drainage through cortical venous system.\n\n• Deep: if any/all drainage is through deep veins.\n\n\n\n• periventricular\n\n\n\n• drainage distinct from other deep venous drainage\n\n\n\n• number of draining veins\n\n\n\n• number of discrete venous channels leaving the nidus\n\n\n\n• number of veins reaching sinus\n\n\n\n• number of draining veins reaching any of these sinuses: superior sagittal, straight, transverse, sigmoid, cavernous, superior or inferior petrosal\n\n\n\n• venous stenosis\n\n\n\n• narrowing of any draining vein outflow pathway in two angiographic views\n\n\n\n• venous ectasia\n\n\n\n• more than double the calibre in any draining venous channel\n\n\n\n• venous reflux\n\n\n\n• flow reversal in any venous outflow pathway in a direction different than that to the nearest venous sinus\n\n\n\n• sinus thrombosis\n\n\n\n• dural venous sinus filling defect\n\n\n\n• feeding arteries\n\n\n\n• arterial structure which displays a flow contribution to the AV shunt on DSA\n\n\n\n• arterial aneurysms\n\n\n\n• parent feeding vessel’s saccular dilatations\n\n\n\n• Moyamoya-type changes\n\n\n\n• pattern of angiographic changes indicating feeding artery occlusion\n\n\n\n• Pial-to-pial collateralisation\n\n\n\n• recruiting of side-by-side pial-to-pial collaterals not part of the nidus\n\n\n\n• Intravascular pressure measurements\n\n\n\n• n/a\n\nRisk of bias was determined by two independent reviewers (SD and HP) using a version of a score devised to determine the methodological quality of case series and case reports,5 modified to expand its application to other study types. For each study, the quality assessment questions used were:\n\n• Diagnosis: Are diagnostic criteria (as defined) for cAVM clearly identified and met?\n\n• Is the method of cerebral angiography described, including the arterial injections, views taken, and what structures are included in a standard view?\n\n• Is the method of calibration described?\n\n• Are the cerebral angiograms reported on by two blinded neuroradiologist(s)?\n\n• Were the patients reported collected over a short period of time in sufficient numbers?\n\n• Is intra-rater reliability reported for each publication?\n\nThe principal summary measures were the number of studies following the JWG terminology and the angioarchitectural fields described.\n\nThis review aimed to assess if the description of cAVM angioarchitecture is standardised according to the JWG criteria and to explore if there are additional features that could be used to describe cAVMs and added to the JWG reporting standards. Additional features could be required to describe cAVMs as shown by some studies. Our objectives were to describe:\n\n1. which of the JWG reporting standards were used,\n\n2. adherence to definitions used in the JWG document,\n\n3. novel angiographic features not mentioned by the JWG, and\n\n4. the profession and experience of those reporting cAVMs.\n\nWe also compared the inter-observer agreement of different studies for the common criteria studied.\n\nPublication and selective reporting biases were assessed.\n\n\nResults\n\nWe identified 4306 publications (Figure 1) and 219 articles were selected for full-text review, reporting the angiogram findings potentially for 54, 148 individuals in total.\n\nMost studies were retrospective (63%), with the remainder being prospective (27.9%), case reports (2.7%), studies that were both prospective and retrospective (2.7%), and educational (3.7%).\n\nThe studies spanned from 2001 to 2020 (the JWG report was published in 2001). The number of patients in each study ranged from 1 to 3923. The median was 120 (interquartile range: 30 to 278). The countries individually publishing the highest number of studies were China (15.5%) and the United States of America (15.1%). Studies from Western Europe, North America and Asia made up 26.5% of studies, with other countries (publishing fewer studies, i.e. one to four studies each) making up 69.9%.\n\nBeijing Tiantan Hospital published more papers than any other centre, with data from this single centre contributing to 26 (74.3%) of the studies from China and 11.9% overall. Several studies used the same study populations, occasionally with a few more cases added due to an extension of study duration by a few years (Table 2). Out of Beijing Tiantan’s 26 studies, the commonest author groups were Lv et al and Tong et al (five studies for each author group) with the same sample population used three times for each of these two author groups (Table 2). The University of California (San Francisco) (18; 8.2%), University of Virginia (Charlottesville) (7; 3.2%), and Columbia University (New York) (6; 2.7%) were the most frequently publishing American institutions.\n\nGiven the clinical importance of predicting haemorrhage, the aim of 65 papers (29.7%) was to test for associations between angioarchitecture and risk of bleeding (including location).1,6–69 Twelve studies tested for an association between angioarchitecture and risk of seizure.70–81\n\nStandard imaging was compared against novel imaging techniques in four studies, and pre-operative imaging was investigated in two studies.82–87 Three studies assessed haemodynamics.28,88,89\n\nEleven papers studied various grading scores.82,90–99 The Spetzler-Martin Grade was the most commonly analysed, but others included the Spetzler-Ponce, Lawton-Young, and Pollock-Flickinger. Out of these 11 studies, seven assessed and proposed different grading systems.92–96,98,99\n\nFour papers assessed the reliability of different cAVM grading scales, and two studies assessed the reliability in describing cAVM angioarchitecture.2,82,90,91,97,100 Agreement ranged from fair to excellent for both inter- and intra-rater comparisons.\n\nAngioarchitectural characteristics were reported in association with treatments: embolisation,17,43,46,92,94,100–129 surgery,6,86,101,110,111,113,114,117,130–145 and stereotactic radiosurgery.44,74,88,51,104,110,113,114,117,120,131,136,146–152\n\nIn those studies that assessed inter-observer agreement, the commonest criteria investigated were size, SMG, venous drainage, and arterial feeders. The lowest scores were 0.62,82 0.46,82 0.56,83 and 0.686 respectively. The highest scores were 0.98,153 0.96,154 0.89,155 and 0.91155 respectively.\n\nOverall, the quality of the reporting studies was poor, with several of the study quality criteria not fulfilled (Table 3). Only 48 out of 219 studies (21.9%) used the definitions recommended by the JWG for some of the features reported (Table 3),7,10,11,14,15,17,19–21,24,26,29,38,40,46–48,52,55,57,58,62,63,66,68,81,143,147,150,156–172 with only 33 publications (15.1%) reporting and specifically mentioning using the JWG standards.\n\nThe list excludes studies which do not describe angioarchitecture in detail e.g. only report location. White boxes indicate criteria fulfilled; dark grey boxes indicate criteria absent. a = JWG standard used; b = cAVM diagnostic criteria; c = DSA method: arterial injections; d = DSA method: views; e = Calibration method; f = Inter-rater reliability assessed; g = Statistics performed.\n\nBiases in the studies were because there was a small population size (less than 100 cases) in 100 studies, a second professional did not independently review angiograms in any of the studies, and there was often a re-analysis of datasets.\n\nThe common angioarchitectural features are listed with the associated number of studies (Figure 2). Most studies described nidus size (175 studies; 78%), location (153; 68%), border (29; 12.9%), venous drainage (173; 76.9%), feeding arteries (88; 39.1%), and the presence of aneurysms (121; 53.8%). No studies described the angiographic features of pial to pial collaterals or Moya-Moya type changes as recommended by the JWG.\n\nMany studies used a variety of the recommended angiographic features, though not necessarily defining these features in the same way as the JWG (Table 4).\n\nThey may have different definitions for these features compared to that stipulated by the JWG.\n\nAlmost all the features described using the JWG guidelines were given different definitions, including, type of feeders, arterial feeders, and haemorrhagic presentation.\n\ncAVM location was not described by the JWG, and this feature had the largest range of definitions. Some specified what constitutes deep, cortical, and/or infratentorial1,15,23,58,173,174 or dichotomised location into supratentorial and infratentorial.20,138,175,176 There were further categorisations into posterior fossa and periventricular by Ma et al.165\n\nVenous ectasia was the feature with the second-most variations of definition. Whereas the JWG defines it as double the calibre change in any draining venous channel, others have described it as 1.5 times larger than the contralateral vessel,177 and two papers are broader in their definitions, describing venous ectasia as a markedly ectatic vein,98 or an abnormal dilatation.59,61\n\nAneurysms were defined as a saccular luminal dilatation of parent feeding vessels by the JWG. Most papers have essentially stated the aneurysm should be double the width of the artery, with only one definition stating the diameter is at least the same as that of the parent vessel.19\n\nNumerous studies described angioarchitectural features which were not mentioned in the JWG report and these are described in Table 5. These features included perinidal angiogenesis, AVM nidus, deep location, and venous varix/pouch.\n\n\n\n• the vascular mass included in the AVM size measurement (Stapf 2003, Stapf 2006, Khaw)\n\n• the junction between the feeding arteries and draining veins, without a capillary bed (Mohr)\n\n\n\n• Vascular network within brain parenchyma between the nidus and feeding artery terminal segment, without visible arteriovenous shunts (Valavanis)\n\n• Indirect supply to the AVM periphery from arterial branches other than the main arterial feeders (Shankar)\n\n• The formation of a new network of arteriocapillaries in the white matter around an AVM in reaction to hypoxia. This is caused by the steal effect from a high flow nidus in the perinidal brain (Taeshineetanakul, Hu)\n\n\n\n• Includes basal ganglia, internal capsule, thalamus, and corpus callosum (Lin)\n\n• The larger portion of the nidus is localised in deep white matter tracts, basal ganglia and thalamus, peri-ventricular regions, or posterior fossa (da Costa 2009)\n\n• Includes the cerebellum, thalamus, basal ganglia, internal capsule, corpus callosum, and brainstem (Hu)\n\n\n\n• Markedly ectatic vein (Lv 2013, Luo)\n\n• Focal dilatations at least twice as large as the vein diameter (Pan 2013)\n\n• Focal aneurysmal dilation in the draining venous system (Daou)\n\n• Proximal draining vein’s focal aneurysmal dilation (Chen 2017)\n\n• Bleb that originates on the nidus venules with no defined relationship with a draining vein (D’Aliberti)\n\n• Change of greater than 200% in the focal venous diameter of any drainage vein (Hu)\n\nThe most common profession conducting these studies were neuroradiologists/neuro-interventionalists (101 studies) and neurosurgeons (60 studies). A neuropathologist was involved in one study.\n\n\nDiscussion\n\nWe have shown that only 33 studies of 219 (15.1%) included in our systematic review explicitly followed the JWG standards since their publication 20 years ago.3 Additionally, most studies reported venous drainage (76.9%), cAVM size (78%), and cAVM location (68%), suggesting these features are frequently considered as cAVM angioarchitecture. These parameters were the most widely used, likely due to their relation to the SMG system.\n\nSince 219 publications were reviewed as providing data on angioarchitecture, it appears that this topic is considered important. Most commonly angioarchitectural features were used to test for associations with outcomes relevant to cAVM such as haemorrhage. Given that overall, the technical quality of publications was low, that most studies were retrospective and from small single centre series, the validity of results from these series could be questioned. Data reported from larger series also lacked the full consideration of angioarchitecture and often the same dataset was used for association studies again compromising the associations reported. In addition, as a large proportion of studies were published by single institutions, the results may not be generalisable to other cAVM populations.\n\nIn those studies that assessed inter-observer agreement, the criteria most frequently used for comparison were size, SMG, venous drainage, and arterial feeders. It is possible that the other criteria were less used as they were more difficult to analyse on imaging.\n\nTwenty years have passed since the publication of the JWG definitions and, not unsurprisingly, several papers have reported on additional aspects of angioarchitecture which the JWG had not considered. These additional features may be helpful in understanding cAVMs and consideration should be given for their inclusion in any future update. These features are perinidal angiogenesis, deep location, venous and arterial dilatation. Angiogenesis is important for the formation and development of a cAVM and its presence may be useful in surgical planning.126 The precise location of a cAVM is crucial with well accepted definitions key for a shared understanding when discussing patient management. Venous dilatation is helpful to describe as it indicates if there may be high or low-pressure flow in the cAVM, with a larger vein reducing the pressure in a cAVM.36,60,152,165,173,174,197 This would be relevant to decide on the management approach. Equally, arterial dilatation20,77,151,177 may imply high-pressure flow in a cAVM, particularly if combined with a single vein of regular dimensions and may have clinical implications.\n\nIn this review, we also observed that pial-pial collaterals and Moya-moya changes were not recorded. This may reflect the difficulty in identifying these features, but also may suggest that they occur infrequently.\n\n\nConclusion\n\nThe JWG publication did clarify that the definitions were parameters to be used in research studies.3 They have also discussed that there were no minimal criteria that should be used, emphasising that the angioarchitectural criteria were based on reasoned speculation. However, given that many of the criteria are likely to be interdependent, and studies are increasingly used to show associations with clinical presentation, this review would support the need to establish another working group to incorporate additional angiographic features and to include more specific and precise definitions for some of the features that were left open to interpretation. We would argue that these recommendations should then be widely publicised and uniformly incorporated into national and local reporting guidelines to help guide research and to ensure that clinicians can appropriately interpret this research with the understanding of the common language.\n\nThis review was not registered as described above. The review protocol can be accessed on BioStudies. The link is https://www.ebi.ac.uk/biostudies/studies/S-BSST1168. The accession number is S-BSST1168.",
"appendix": "Data availability\n\nBioStudies. Review of angioarchitecture literature SD. DOI: https://www.ebi.ac.uk/biostudies/studies/S-BSST1168BioStudies.\n\nThe raw data is in two files titled:\n\n- ‘Review of angioarchitecture literature SD’ and\n\n- ‘Review of angioarchitecture literature quality SD’.\n\nThe content is raw data from the papers used in the systematic review. The accession number is S-BSST1168.\n\nBiostudies. PRISMA checklist. DOI: https://www.ebi.ac.uk/biostudies/studies/S-BSST1168. The flow diagram is in Figure 1.\n\n\nAcknowledgements\n\nThe authors would like to thank the Natalie Kate Moss Trust for their generous support. PK and AP-J are supported by the Stroke Association (TSA LECT 2017/02; SA L-RC 19\\100000).\n\nThere are no competing interests to declare.\n\n\nReferences\n\nYamada S, Takagi Y, Nozaki K, et al.: Risk factors for subsequent hemorrhage in patients with cerebral arteriovenous malformations. J. Neurosurg. 2007; 107(5): 965–972. 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Publisher Full Text\n\nMotebejane M, Royston D, Kabera G, et al.: Demographic and angioarchitectural features associated with seizures presentation in patients with brain arteriovenous malformations in Durban, KwaZulu-Natal, South Africa.Interdiscip. Neurosurg. Adv. Tech. Case Manag.2018; 11: 14–18. Publisher Full Text\n\nNishino K, Hasegawa H, Morita K, Fukuda M, Ito Y, Y. F.: Clinical characteristics of arteriovenous malformations in the cerebellopontine angle cistern.J. Neurosurg.2017; 126(1): 60–68. PubMed Abstract | Publisher Full Text\n\nOulasvirta E, Koroknay-Pál P, Hafez A, et al.: Characteristics and Long-Term Outcome of 127 Children With Cerebral Arteriovenous Malformations. Neurosurgery. 2019 Jan 1; 84(1): 151–159. PubMed Abstract | Publisher Full Text\n\nPatel MC, Hodgson TJ, Kemeny AA, et al.: Spontaneous Obliteration of Pial Arteriovenous Malformations: A Review of 27 Cases. AJNR Am. J. Neuroradiol.2001; 22: 531–536. PubMed Abstract\n\nPekmezci M, Nelson J, Su H, et al.: Morphometric characterization of brain arteriovenous malformations for clinical and radiological studies to identify silent intralesional microhemorrhages. Clin. Neuropathol. 2016 May-Jun; 35(3): 114–121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRobert T, Blanc R, Ciccio G, et al. E-053 Multi-Modality Management of Posterior Fossa Arteriovenous Malformations: Clinical and Angiographic Outcomes. J. Neurointerv. Surg. 2014; 6:A63.1, A6A63. Publisher Full Text\n\nSchwartz ED, Hurst RW, Sinson G, et al.: Complete regression of intracranial arteriovenous malformations. Surg. Neurol.2002; 58: 139–147.\n\nShakur SF, Brunozzi D, Ismail R, et al.: Effect of Age on Cerebral Arteriovenous Malformation Draining Vein Stenosis.World Neurosurg.2018; 113: e654–e658. Publisher Full Text\n\nShakur SF, Valyi-Nagy T, Amin-Hanjani S, et al.: Effects of nidus microarchitecture on cerebral arteriovenous malformation hemodynamics.J. Clin. Neurosci.2016; 26: 70–74. Publisher Full Text\n\nSheng L, Li J, Li H, et al.: Evaluation of cerebral arteriovenous malformation using ‘dual vessel fusion’ technology. J. NeuroIntervent. Surg.2014; 6: 667–671. PubMed Abstract | Publisher Full Text\n\nTogao O, Hiwatashi A, Yamashita K, et al.: Acceleration-selective arterial spin labeling MR angiography for visualization of brain arteriovenous malformations.Neuroradiology.2019; 61: 979–989. Publisher Full Text\n\nTritt S, Ommer B, Gehrisch S, et al.: Optimization of the Surgical Approach in AVMs Using MRI and 4D DSA Fusion Technique. Clin. Neuroradiol. 2017; 27(4): 443–450. PubMed Abstract | Publisher Full Text\n\nUnlu E, Temizoz O, Albayram S, et al.: Contrast-enhanced MR 3D angiography in the assessment of brain AVMs.Eur. J. Radiol.2006 Dec; 60(3): 367–78. PubMed Abstract | Publisher Full Text\n\nWrede KH, Dammann P, Johst S, et al.: Non-Enhanced MR Imaging of Cerebral Arteriovenous Malformations at 7 Tesla. Eur. 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}
|
[
{
"id": "211337",
"date": "02 Nov 2023",
"name": "Nitin Mukerji",
"expertise": [
"Reviewer Expertise Cerebrovascular Neurosurgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors have picked out a standard method of reporting/describing AVMs in literature and attempted to establish compliance via a retrospective review. While the work done is commendable, well researched and drafted appropriately; there are a few criticisms:\nThe reason why there is not much compliance with JWG guidelines is that every publication uses one of the available classifications, Spetzler-Martin, Spetzler-Ponce, Lawton-Young or Flickinger-Pollock - that is enough to give a basic idea of what one is dealing with and the granularity of the JWG is not always required.\n\nWith a lot of papers coming from one institution, in China - whether or not there is awareness of the JWG guidelines there is questionable - the conclusions are probably to be taken with some skepticism. It would help to know if the compliance was better in 'Western' papers.\n\nBias issues and tests such as 'reporting by two independent neuroradiologists' - I think are too harsh; this rarely, if ever happens.\n\nI think this paper fundamentally is missing a 'premise' - what is it that the authors wish to convey? If the aim is to relate the fact that there is an obscure guideline most don't know about and hence nobody follows it - then; it is a wasted effort - most clinicians who deal with AVMs are aware of this. If the aim is to propose a new guideline and hence create the preamble that sufficient chaos exists in reporting - then that is not clear. The results and discussion needs to be written clearly to reflect this premise.\n\nSometimes the reason certain aspects are not reported ie. venous stenosis, ectasia...etc - is that they do not exist; that seems not to have been acknowledged.\nOtherwise, a good manuscript - but the message needs to be clearer.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": [
{
"c_id": "12050",
"date": "07 Oct 2024",
"name": "Suparna Das",
"role": "Author Response",
"response": "We have addressed all the comments and we have modified mainly the introduction and discussion, but also some of the results."
}
]
},
{
"id": "264835",
"date": "08 May 2024",
"name": "Mustafa Ismail",
"expertise": [
"Reviewer Expertise Vascular Neurosurgery",
"General Neurosurgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors reported a systematic review about \"Reporting of angiographic studies in patients diagnosed with a cerebral arteriovenous malformation: a systematic review\" and I congratulate them for this work. There are a few points to consider in this review:\n\nEnhancement of the Introduction:\nThe introduction should be expanded to more clearly articulate the clinical implications of inconsistent reporting standards. Detailing the direct impacts on patient outcomes and treatment efficacy can better highlight the necessity for standardized reporting.\n\nImportance of Citing the JWG Standards:\nThe article should more strongly emphasize the significance of the Joint Writing Group (JWG) standards in establishing a uniform framework for reporting. Additionally, it should address dissenting views regarding the sufficiency of these guidelines by presenting evidence from the review, demonstrating the clarity and comparability brought by adherence to JWG standards.\n\nBroadening the Discussion Section:\nThe discussion should be expanded to incorporate a wider range of arguments regarding the variations in adherence to JWG standards across different medical practices or regions. It should analyze the implications for multi-center studies and longitudinal research and include perspectives from various stakeholders like clinicians, researchers, and healthcare policymakers.\n\nInclusion of a Limitations Section:\nA dedicated section on limitations should be added to discuss both the methodological constraints of the review, such as potential publication bias, and the practical challenges of applying JWG standards universally, like variations in technological access across health systems.\n\nRationale for Mandatory JWG Citations:\nThe article should provide a robust justification for the inclusion of JWG citations in all related studies, explaining how these references enhance the academic rigor and credibility of research publications. It should also critique reasons given by some authors for omitting these standards, suggesting areas where JWG criteria could be expanded or adapted.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": [
{
"c_id": "12051",
"date": "07 Oct 2024",
"name": "Suparna Das",
"role": "Author Response",
"response": "We have addressed all the comments and we have modified mainly the introduction and discussion, but also some of the results."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1252
|
https://f1000research.com/articles/13-25/v1
|
08 Jan 24
|
{
"type": "Research Article",
"title": "Household resilience of women migrant worker sellers of Jamu Gendong",
"authors": [
"Dian Diniyati",
"Ary Widiyanto",
"Sanudin Sanudin",
"Eva Fauziyah",
"Budiman Achmad",
"Endah Suhaendah",
"Aditya Hani",
"Muhtar Muhtar",
"Danarti Danarti",
"Tri Sulistyati Widyaningsih",
"Aji Winara",
"Sri Najiyati",
"Rukmini Nugroho Dewi",
"Dian Diniyati",
"Sanudin Sanudin",
"Eva Fauziyah",
"Budiman Achmad",
"Endah Suhaendah",
"Aditya Hani",
"Muhtar Muhtar",
"Danarti Danarti",
"Tri Sulistyati Widyaningsih",
"Aji Winara",
"Sri Najiyati",
"Rukmini Nugroho Dewi"
],
"abstract": "Background The selling of Jamu Gendong (an Indonesian traditional herbal medicine), is closely associated with the informal work of women who migrate to different regions. In Sukoharjo Regency and Wonogiri Regency, Central Java Province, the pressing need to meet household necessities in their places of origin compels women to assume the role of breadwinners. Therefore, this research aimed to identify the livelihood capital and resilience of migrant women selling jamu gendong.\n\nMethods The study was conducted in Ciamis Regency, West Java Province, Indonesia, in November 2022, using quantitative and qualitative methods. Primary data were collected through structured questionnaires and in-depth interviews. The sample comprised 51 women selected through snowball sampling and actively involved in selling Jamu Gendong, along with six key individuals from relevant agencies.\n\nResults The results showed that the households of migrant women selling jamu gendong survived and adapted to the migration destinations to prevent poverty. This was attributed to the livelihood strategy of business diversification. In this context, migration was exclusively practiced by women without family members who rented accommodation together. This research identified different forms of capital these women possess, including their productive age and skills in preparing jamu gendong, physical capital encompassing road infrastructure, marketplaces, access to health and education facilities, and natural, social, and financial capital.\n\nConclusions The findings contribute to a comprehensive understanding of the resilience demonstrated by migrant women selling jamu gendong. However, further research should be conducted in areas beyond the city center to obtain a holistic view of their resilience.",
"keywords": [
"Jamu",
"livelihood assets",
"resilience",
"women"
],
"content": "Introduction\n\nMigration is the movement of individuals or groups across spatial boundaries, involving a change of residence (Kok, 1999). It is a global phenomenon that has been present throughout human history (Castelli, 2018). People relocate for various reasons, including necessity, personal desire, or coercion, often driven by poverty or the pursuit of better economic opportunities in different locations (Schrover, 2022). Approximately 258 million individuals migrate worldwide alongside considerable migration within individual countries, including Indonesia (Azzam, 2017). Individuals who migrate are commonly referred to as migrants, indicating movement from a customary place of residence, within their country or across international borders (IOM, 2023). Among the various regions in Indonesia, West Java stands out for having the highest number of internal migrants and is established as a prominent migration destination (Badan Pusat Statistik Provinsi Jawa Barat, 2021). Ciamis Regency within West Java has attracted migrants from different origins, including Sukoharjo Regency, Surakarta City, and Wonogiri Regency in Central Java Province. These three regions have significant migrant populations, predominantly engaged in informal sector occupations within the destination areas, such as selling jamu gendong. Jamu gendong is a traditional Indonesian drink, generally made from fresh organic ingredients, in liquid form which is contained in several bottles then arranged neatly in baskets, and sold by carrying them in cloth by women who go around residential areas, markets and bus station (Latifa et al., 2020; Limyati & Juniar, 1998; Pemerintah Kota Surakarta, 2022; Wulandari & Azrianingsih, 2014).\n\nSelling jamu gendong is a form of informal work commonly practiced by women. According to Badan Pusat Statistik (2022b), the proportion of female informal workers (66.36%) surpassed that of their male counterparts (53.68%) in 2021. This phenomenon can be attributed to various factors, such as the husband’s low income, limited capital, low educational attainment, aspirations to improve the family’s economic situation, family business continuation, and social and environmental factors (Mustofa et al., 2022).\n\nJamu gendong sellers migrate to expand their market reach, particularly in densely populated regions of Indonesia, such as West Java Province (Badan Pusat Statistik, 2022a). Migration in Indonesia is motivated by several factors, including the pursuit of better job prospects and higher income to provide sufficient welfare for migrants and families, often in response to the lack of employment opportunities in their hometown (De Royer et al., 2014), a desire to earn cash income (Mulyoutami et al., 2015), greater employment opportunities outside the village, and the presence of friends or family members who extend invitations or have already relocated (Fauziyah et al., 2015). The migration decision is influenced by age, land ownership, and income (Wijaya & Syairozi, 2020).\n\nTo effectively adapt to the circumstances at the migration destination, jamu gendong sellers employ a livelihood strategy known as resilience (Saraswati & Dharmawan, 2014). Resilience is defined as the capacity of a socioecological system to absorb disturbances, undergo changes, and retain its core functions, structure, and identity (Nabin & Sgro, 2013). (Grotberg, 1999) identified several sources of resilience, namely external support (I Have), individual ability (I Am), and social and interpersonal skills (I Can). Resilience encompasses the dimensions of resistance and toughness. It does not entail avoiding or eliminating adversity but rather involves navigating through challenges effectively and emerging stronger.\n\nResilience must be integrated with empowering and sustaining community livelihoods. The strategy encompasses constructing a comprehensive livelihood system of various methods to enhance life circumstances. This system must be supported by various livelihood assets (Dharmawan, 2007a), including human, physical, natural, social, and financial capital (Ellis, 2000a).\n\nThe households of female Jamu Gendong workers must compete with others to meet subsistence needs (Badan Pusat Statistik Kabupaten Ciamis, 2023). The percentage of informal workers in Ciamis Regency is greater (69.48%) than formal workers (30.52%). This research identifies the livelihood capital and resilience possessed by migrant women selling jamu gendong in conducting their livelihood activities. The findings provide valuable insights into the experiences of migrant women, as the existing literature predominantly focuses on male migrants (Schrover & Moloney, 2013). Migrant women remain largely overlooked, despite the significant impact of female migration on various aspects of their public and private lives, including worker participation, occupational distribution, religious beliefs, household responsibilities, and autonomy and self-esteem (Pedraza, 1991).\n\n\nMethods\n\nThis research has applied Ethical approval for research involving respondents. Ethical approval (ethical clearance) measures the ethical acceptability of a series of research processes. We obtained research ethical clearance approval from the BRIN Ethics Commission before the research began as a reference for upholding the values of integrity, honesty, and fairness in conducting research. In ethical clearance, there is informed consent, which guarantees the confidentiality of all information provided by participants. The ethical approval is included in the Ethics Commission for the Social Humanities Decree of the National Research and Innovation Agency No. 454/KE.01/SK/10/2022 dated 12 October 2022.\n\nWe also carried out the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist before conducting the research. Regarding respondents and interviewer, we ensure that 1) there was no relationship established before study commencement; 2) participants know about the researcher’s reasons for collecting data; and 3) There was no bias, assumptions, reasons, or interests in the research topic for the interviewer/facilitator. Consent to be interviewed was given by the respondent in writing, by the respondent signing the questionnaire form, before the interview was conducted.\n\nThis research used quantitative and qualitative methods to obtain more comprehensive, valid, reliable, and objective data (Masrizal, 2012) in Ciamis Regency, West Java Province (Figure 1). In November 2022, Ciamis Regency was selected as the research location because it is a destination for migrating residents outside the area who become informal workers selling jamu gendong, specifically from Sukoharjo Regency, Surakarta City, and Wonogiri Regency, Central Java Province.\n\n(This figure is an original figure produced by the author(s) for this article).\n\nThe data collected comprised primary and secondary data. Primary data were collected through structured questionnaires and in-depth interviews using an interview guide. Structured interviews were conducted with respondents selected purposively by looking for jamu gendong sellers in shops. Secondary data was obtained from various sources such as documents and literature searches through websites related to the research. Literature is searched on several main indexers, namely Scopus and Google Scholar. Articles were searched using keywords such as “jamu gendong”, “herbal medicines”, “household resilience”, “migration”, “female worker”, and “livelihood”.\n\nBased on the research problems mentioned in the introduction, in this study research variables were compiled that influence the level of resilience of herbal medicine sellers as migrants. The level of resilience of households selling jamu gendong is influenced by the household income structure which includes a diversity of income sources. Ownership of assets by sellers of jamu gendong will influence the level of resale. The types of assets that will have an influence are Human Capital, Physical Capital, Natural Capital, Social Capital, Financial Capital.\n\nThis research used 51 participants who were selected by using snowball sampling. The participants were selected because of their experiences in selling jamu gendong for a minimum of two years. The research was conducted for the first time; therefore it used the specific questionnaires which were not used before. The suitability of questionnaires were evaluated before implemented in research activity. The final questionnaire and interview guide are provided as Extended data (Widyaningsih, 2023).\n\nIn-depth interviews were conducted with six informants selected deliberately from related technical agencies, namely, officials at the Agriculture and Food Crops Agency of Ciamis Regency, Cooperatives, Small and Medium Enterprises, the Trade Agency of Ciamis Regency, the Regional Planning and Development Agency (Bappeda) of Ciamis Regency, West Java Regional VII Forest Service Branch with one of the working areas being Ciamis Regency, and the Center for Implementation of Environmental and Forestry Instrument Standards (BPSI LHK) Ciamis. Interviews were conducted with deliberately selected respondents. Determining respondents uses the snowball technique to identify the flow of data needed from one respondent to another.\n\nInterviews were carried out by researchers who have more than 10 years of experience in social research. The total interview time was three months, depending on the respondent’s time availability. The majority of respondents were individuals, only a few were interviewed in groups. The interview media uses audio recordings, with prior approval from the respondent.\n\nThe Household Resiliency Index (HRI) is a simple, user-friendly tool that can be used to assess and classify households. The HRI has a quantitative questionnaire that assigns points to each response. The questionnaire includes variables that were carefully chosen to measure the impact of economic strengthening interventions on household assets, income, expenses, and health outcomes.\n\nThree parameters are measured, i.e., asset and income, expenses, and health outcomes. Indicator for each parameter can be seen in Table 1, Table 2, and Table 3. Each parameter consists of several indicators which are scored according to the HRI guide for measuring household economic resilience developed by the Alliance for Child Protection in Humanitarian Action (2011). Assets and income = 35 points, including the indicator of monthly savings of max 10 points, livestock owned of max 10 points, and an increase in monthly income of max 5 points. Expenses = 35 points, including the number of meals per day max 10 points, ability to pay for basic needs max 10 points, ability to invest in income-generating activities (IGAs) max 15 points. Health outcome = 30 points, including Ability to pay for children’s school fees (level) max 10 points, Household members fully covered by health insurance max 5 points, Household food production level max 15 points. Decision criteria used as follows:\n\n• Score 0-30 = Category 1 (household in destitution)\n\n• Score 31-60 = Category 2 (Households Struggling to Make Ends Meet)\n\n• Score 61-100 = Category 3 (Households Prepared to Grow)\n\n\n\na. No savings\n\n\n\nb. 100–9,999\n\n\n\nc. 10,000–19,999\n\n\n\nd. 20,000–50,000\n\n\n\ne. Above 50,000\n\n\n\na. Don’t have\n\n\n\nb. 1–9\n\n\n\nc. Ten or more\n\n\n\na. Don’t have additional income\n\n\n\nb. Have additional income\n\nAfter all the data was collected, the data was tabulated using the Microsoft Excel program for each parameter. The calculation results are then explained descriptively. Secondary data in related literature was used to strengthen, contrast, or compare research findings.\n\n\nResults\n\nIncome structure is the composition of household income from various livelihood activities carried out by all household members (Dharmawan, 2007b). Based on the results, the average income of respondents is IDR 55,664,492/year. The structure of the respondents’ income is divided into two groups: income from selling jamu gendong and income from spouses. Figure 2 shows that the family’s income is dominated by selling jamu gendong at 62.5%, while the remainder comes from the spouse’s income. Respondents use a dual income pattern in which husband and wife work together to earn a living to meet their needs (Sumersi et al., 2021). According to Ellis (2000b), individuals and households diversify their livelihoods for two reasons, namely, need or choice.\n\n(This figure is an original figure produced by the author(s) for this article).\n\nFurthermore, the couple’s primary occupation revolves around the role of sellers, with a particular emphasis on fast food, specifically meatballs. Five respondents (9.8%) did not have a partner, while nine (17.6%) had unemployed partners, resulting in a lack of supplementary income. The significance of women’s earnings as jamu sellers in bolstering family income is illustrated in Figure 3. By actively participating in the workforce, women effectively assist their husbands in sustaining the family’s economic stability and augmenting the total income (Maradou et al., 2017; Musa et al., 2015), and providing a safety valve or household support to meet basic daily needs (Ramli et al., 2020). Women’s involvement in economic activities must be acknowledged, even though there are differences in work between men and women.\n\n(This figure is an original figure produced by the author(s) for this article).\n\nAccording to Fridayanti and Dharmawan (2015) and Salatalohy (2019), income from a partner is part of a diversification strategy or a double income pattern (Parker & Peterson, 2016; Smith, 2019). Even though the role of women is more dominant, the household income structure of jamu sellers can be categorized as a model of shared responsibility in which all members contribute to family income and share the responsibility for expenses. Each family member may have a source of income and contribute according to their means (Johnson & Williams, 2018; Miller, 2017). The income is used to meet the family’s needs together (Jackson & Davis, 2015; Miller, 2017). This model promotes participation and shared responsibility in managing family finances.\n\nHousehold expenditure refers to all the expenses associated with purchasing goods and services to meet basic needs (Illahi et al., 2018). These expenditures can be broadly categorized into food and nonfood expenditures (Alfrida & Noor, 2017). Food expenditures typically include items such as rice, vegetables, side dishes, oil, etc. Nonfood expenditures include clothing, transportation, health, communication, water, electricity, taxes, LPG for cooking, and other nonfood consumption.\n\nAccording to the data presented in Table 4, the expenditure on food accounts for approximately 49.7% of household expenses, while nonfood slightly surpasses food expenditure at 50.3%. Trihastono et al. (2021) found that as household income increased, the proportion of spending on food tended to decrease, while the percentage allocated to nonfood items became larger. The higher the household income, the smaller the proportion of consumption allocated to food. Several factors influence the amount of household consumption, including economic, demographic, and noneconomic factors (Illahi et al., 2018). Moreover, food expenditure serves as an indicator of economic well-being (Haq, 2009). In societies where the percentage of spending on food is significantly lower than on nonfood items, greater prosperity is often observed. Household expenses for jamu gendong traders are shown in Table 4.\n\nAccording to research conducted by the World Bank (2007), impoverished households in developing nations allocated a significant portion of their income, up to 70%–80%, toward food expenses. Expenditure on food purchased from jamu sellers accounted for nearly 50% of their income. Even though the World Bank (2007) considered this expenditure relatively modest, it remained the most significant component compared to others. The two primary nonfood expenses were directed toward educating children and providing transfers to families in their places of origin. Interestingly, this finding contradicted previous research that identified housing needs, such as rent or mortgage repayments (UN-Habitat, 2003) and health costs (World Health Organization, 2008) as the primary nonfood expenses.\n\nThe relatively smaller amount allocated to these categories can be attributed to the transfer activities directed toward families in their places of origin. Meanwhile, the monetary transfers made by migrant workers residing in cities are crucial in reducing poverty levels in their villages. The recipients of these transfers can utilize them to fulfill basic needs of food, housing, education, and health (Rachmaniah & Suryahadi, 2016). They also underscore the benefits of migration, which provide village families with access to economic resources, information, and expanded social networks.\n\nLivelihood is defined as a means of earning a living (Chamber and Conway, 1991). According to DFID (2001), sustainable livelihoods are needed for resilience, which is supported by five assets: human resources (capital), natural, physical, financial, and social capital. The livelihood assets owned by women selling jamu in Ciamis Regency are as follows.\n\n1. Human Capital\n\nHuman capital encompasses the aptitudes, knowledge, capabilities, and good health that empower individuals to pursue diverse livelihood strategies and attain their objectives (DFID, 2001). It refers to an individual’s intrinsic and acquired assets, including skills, abilities, and competencies (Quandt, 2018). This concept entails proficiency, sound health, and the capacity to engage in various life strategies and endeavors to achieve livelihood goals (Shen et al., 2009).\n\nWithin the jamu-selling community, individuals aged 40–49 years (47.06%) dominate the productive age group. Their education level predominantly comprises high school graduates (Junior High School and Senior High School), accounting for 60.78%, while those who did not attend or complete elementary school make up 39.22%. The level of education did not reduce the respondents’ interest in selling Jamu Gendong, as expressed by Mrs. Wn (54 years), who has been a seller since the age of 14: “I only went to school until I graduated from elementary school, but I have to sell jamu to help the family’s economy.” Therefore, the respondents are enthusiastic and motivated to survive in the face of economic shocks. They also have knowledge and skills in preparing jamu as a legacy from their ancestors that is still maintained. The distribution of respondents based on human capital is presented in Figure 4.\n\n(This figure is an original figure produced by the author(s) for this article).\n\nAssistance to Jamu Gendong sellers is primarily from family members, with 56.86% of respondents indicating that they receive support from their relatives. The remaining sellers handle the business themselves because they do not reside with family members. The absence of hired workers is not solely motivated by cost reduction but also by personal preference and the satisfaction derived from mixing the herbs. Beyene et al. (2023) stated that male-headed households were more resilient at meeting food needs. However, looking at the human capital condition of jamu sellers, women are also tough and play a significant role in meeting family needs. They encounter higher risks compared to their husbands, particularly in marketing. In addition to the necessity to visit customers, women are also susceptible to physical violence, such as robbery and verbal abuse (Perry et al., 2020). Employment within the informal sector often fails to provide favorable conditions for decent work because it lacks security and legal protections. These sellers may lack proper channels or mechanisms to voice their grievances or assert their rights. The jamu sellers encounter challenges while selling that are often not reported to their husbands (Vijayalakshmi et al., 2022).\n\n2. Physical Capital\n\nPhysical capital comprises basic infrastructure and production goods needed to support livelihoods (DFID, 2001). Infrastructure consists of changes in the physical environment that helps people meet their basic needs and become more productive. Produced goods are tools and equipment that people use to function more productively. Physical capital refers to access to services and infrastructure (Adato & Meinzen-Dick, 2002), including skills, knowledge, education, health, and access to the family workforce (Tacoli, 1999). It contributes to the local environment, including housing, public places, industries, bridges, dams, harbors, and shelters, as well as includes vital facilities such as electricity, water, telephone, and gas.\n\nBased on Figure 5, the conditions of some of the Jamu Gendong sellers’ facilities are available at their place of residence, making it easier to live and conduct business. Generally, jamu sellers select to live in downtown Ciamis by renting small houses.\n\n(This figure is an original figure produced by the author(s) for this article).\n\nJamu gendong vendors can capitalize on the existing physical infrastructure, including well-maintained roads and traditional markets that offer a wide range of equipment for producing and marketing jamu. Additionally, nearby health facilities are conveniently accessible, enabling jamu sellers to access necessary healthcare services. Educational institutions, such as schools, are also near their surroundings.\n\n3. Natural Capital\n\nNatural capital refers to the inherent natural resources and elements that contribute to carrying capacity and provide valuable benefits to human livelihoods (DFID, 2001). It holds particular significance for individuals who rely on natural resource-based activities as a primary or partial source of income (Sharafi et al., 2018). These resources comprise various components, including land, water, mines, livestock, and other natural resources. Examples of natural capital are ownership of agricultural land, forests, pastures, water resources, and mineral industries (Nasrnia & Ashktorab, 2021). Natural capital that generates carrying capacity and creates value for the livelihoods of jamu sellers includes the availability of raw materials for making jamu from the surrounding environment. According to 92.16% of respondents, there was no difficulty in obtaining raw materials. Raw materials can be obtained at traditional markets or from the gardens and rice fields of the surrounding community, as stated by 41.18% of respondents. Availability is the main natural capital for the resilience of the jamu business. Furthermore, other assets, such as gardens, rice fields, and livestock, are only owned by a small proportion of jamu sellers, as shown in Figure 6.\n\n(This figure is an original figure produced by the author(s) for this article).\n\n\n\n4. Social Capital\n\nSocial capital is a valuable resource used for pursuing livelihoods, encompassing networking, group affiliations, and mutual trust (DFID, 2001). It comprises networks, groups, associations, relationships, trust, and interactions (Adger et al., 2003). Individuals and communities can access resources and capital through communication and relationships. Social assets are the social resources people leverage to make a living (Nasrnia & Ashktorab, 2021).\n\nFor jamu sellers, the social capital they develop primarily revolves around the community of fellow jamu sellers, which serves as a platform for interaction and problem-solving among peers. The physical proximity of their residences, indicated by 92.16% of respondents, enables close connections and fosters strong ties among jamu sellers (Figure 7).\n\n(This figure is an original figure produced by the author(s) for this article).\n\nFinancial capital refers to the resources that individuals use to achieve their life objectives. These resources encompass reserves or supplies that are owned by individuals or held by financial institutions. Financial capital includes a regular flow of funds, such as income, expenses, savings, accounts payable, and assistance (DFID, 2001). It encompasses various forms of financial resources, including cash, bank accounts, savings, income, investments, credit, current assets, pension rights, allowances, grants, financial remittances, and household property (Nasrnia & Ashktorab, 2021).\n\nAccording to the findings, a significant majority of respondents assist their husbands while also engaging in additional income-generating activities, such as working as masseurs or selling meatballs and food. The financial assets are predominantly allocated toward household expenses, primarily to meet the needs of children and families residing in the area of origin. Furthermore, 76.47% of jamu sellers possess noncash savings, and 84.31% have bank accounts, as shown in Figure 8. Most respondents (80.39%) can access loans or credit from banks and other institutions. Households selling jamu have savings to use as needed. For instance, one of the respondents, Miss St (52 years old), mentioned that she not only saves in a bank account but also allocates a portion of her income toward building a house in her hometown and supporting her children’s education. Additionally, 21.57% own gardens and 31.37% possess rice fields in their hometowns. In addition to their role as natural capital, owning rice fields and gardens significantly contributes to the saving capacity of households.\n\n\nDiscussion\n\nWomen selling jamu not only play a role in generating additional income but also build capital to survive and be able to face various crises. They can do so through access to a job (I Have), utilizing abilities (I Am), and the interpersonal skills developed by the jamu seller. The HRIs are ranked by 43 women jamu sellers (84.31%) in Category 2, eight (15.69%) in Category 3, and zero respondents in Category 1, as shown in Table 5.\n\nThe resilience exhibited by the families of women who sell jamu is closely intertwined with the women’s lifestyles and work ethic. The inhabitants of Central Java are renowned for their strong work ethic and philosophical beliefs, such as “urip kudu dilakoni” (life must be lived) and the necessity of being “gemi” (thrifty). This philosophy reflects an optimistic outlook on life, enabling individuals to thrive in other communities and gradually achieve affluence (Gianawati, 2017; Murdiyastomo, 2015).\n\nThe households of female jamu sellers in Category 2 struggle to make ends meet. These households have been able to meet their basic needs and have saved a limited amount. The savings are primarily in the form of cash, gold jewelry owned by the wife, motorbikes, and portfolio investments. However, these households encounter difficulties when it comes to investing in other productive ventures.\n\nAmong the respondents, eight households fall into Category 3, representing families poised for growth. These households have met their basic needs and also achieved some level of prosperity. The women are not solely focused on increasing their income but on cultivating skills, establishing connections, and possessing the necessary capital to invest in other businesses. They maintain physical assets and savings in their places of origin and engage in ventures in other communities, such as constructing rental properties and establishing savings and loan enterprises. Successful migrants typically expand their businesses promptly after accumulating capital (Mulyoutami et al., 2015).\n\nHousehold members in Categories 2 and 3 can easily access free health services through the Healthy Indonesia Card (KIS) program that aims to ease the burden on people with low incomes to access health services (Simbolon et al., 2019). These households can also finance their children’s education beyond the educational background of their parents. According to Hazani et al. (2020), women’s contributions play a crucial role in family economies. On average, they effectively manage their time, balancing responsibilities within the household and in public settings. Women contribute to increasing the family’s income by assisting in meeting daily expenses, generating additional income, accumulating business and investment capital, saving, and covering costs related to healthcare and education.\n\nEnvironmental changes (Mallick et al., 2023) and limited resources affecting individuals, households, or social groups (Mallick et al., 2023), along with the predominance of dryland agriculture resulting in insufficient agricultural production to meet household needs (Nienkerke et al., 2023), have resulted in a decline in income. Consequently, individuals seek alternative sources of income, with migration being one of them (Sobczak-Szelc & Fekih, 2020). Generally, migration occurs from regions experiencing low economic growth, with individuals seeking better livelihood opportunities to increase their family’s income. The household economic strategy for rural communities migrating to urban areas involves engaging in diverse economic activities among family members to establish multiple alternative sources of income and enhance resilience to change (Hamidah & Santoso, 2021). In such cases, off-farm migration involves pursuing nonagricultural/nonland-based businesses.\n\nJamu sellers, who are predominantly immigrants, employ various strategies to augment their income and optimize household expenditures. This pattern is also evident among Subak farmers in Bali who migrate to cities, employing survival strategies through multiple income streams and developing social networks to bolster income and preserve their cultural heritage (Darmawan et al., 2021). According to Hidayah et al. (2020), livelihood strategies carried out by households entail both economic and social strategies. The economic strategy is conducted by carrying out a double income pattern, using household workers and migration, while the social strategy is based on existing kinship ties.\n\nSome of the strategies for fulfilling a living carried out by women selling jamu include:\n\n1) Diversifying business activities, particularly by establishing dry food businesses, is important for households seeking to diversify their sources of income in both urban and rural areas (Khan & Morrisey, 2023). Despite being engaged in jamu sales, which involve a manufacturing process lasting 1–3 h between 03.30 and 05.00 WIB, with most sales occurring between 06.30 and 11.30 WIB, jamu sellers still have available time to pursue additional income-generating work, such as selling dry food.\n\n2) Migrating from one’s place of origin to another city without family members (husband and children). Family members remain in their place of origin to manage the land and assets, while the women who sell jamu return to their place of origin every month or two. This strategy is implemented to maintain normalcy and ensure that children can continue attending school in their home locality.\n\n3) Living with a jamu seller who is a relative or neighbor from the same place of origin is a deliberate strategy aimed at facilitating coordination and communication. Additionally, it reduces expenses and increases savings that can be sent back to their places of origin as remittances. The presence of friends or relatives who have previously migrated to the same destination area plays a crucial role in establishing a network of migrants (Massey et al., 1993).\n\nIn conclusion, the households of migrant women engaged in the sale of jamu were proven to have the ability to survive, improve their family’s economic conditions, and escape from poverty. Most of the Jamu Gendong sellers had left the impoverished conditions of households struggling to make ends meet, and a small number were ready to grow. This condition was supported by the ability to implement a livelihood strategy through business diversification. Migration was only carried out by women selling jamu, who rented a place to live together and combined it with a dual income strategy. The findings indicated that hard-working women overcame high economic and social pressures by developing strategies for economic survival and dealing with different challenges.\n\nThe living capital of migrant women selling jamu consisted of human capital in the form of productive age and skills in preparing jamu, physical capital in the form of roads, markets, health and education facilities, natural capital in the form of raw materials, social capital in the form of a community of Jamu Gendong sellers, and financial capital in the form of access to financial facilities. These five types of capital were owned and used by migrant women selling jamu in the form of a livelihood strategy.\n\nIt is recommended that the capabilities of these women be enhanced through training and counseling sessions focused on modern jamu processing techniques, disseminating accurate information regarding the proper utilization of jamu, and fostering marketing acumen. These recommendations should not be limited to the migration destination areas but should also extend to stakeholders in home areas.",
"appendix": "Data availability\n\nThe interview transcripts cannot be shared publicly as they cannot be fully deidentified. Readers can request access from the corresponding author (aryw002@brin.go.id).\n\nFigshare: Data Jamu Gendong.xlsx. https://doi.org/10.6084/m9.figshare.23798202 (Widyaningsih, 2023).\n\nThis project contains the following underlying data:\n\n- Research questionnaire of Jamu Gendong.pdf\n\n- Interview guide of jamu gendong research.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe thank Mr Bambang Pudjianto who helped during the data collection.\n\n\nReferences\n\nAdato M, Meinzen-Dick RS: Assessing the impact of agricultural research on poverty using the sustainable livelihoods framework. IFPRI; 2002. No. 581-2016-39396.\n\nAdger WN, Huq S, Brown K, et al.: Adaptation to climate change in the developing world. Prog. Dev. Stud. 2003; 3(3): 179–195. 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SMERU Working Paper, No. 21/2016.2016.\n\nRamli K, Tambani GO, Kotambunan OV: Kontribusi Perempuan Terhadap Pendapatan Keluarga Di Desa Pentadu Timur Kecamatan Tilamuta Kabupaten Boalemo. Akulturasi. 2020; 8(2): 164–168.\n\nSalatalohy A: Strategi dan Struktur Nafkah Rumah Tangga Petani Agroforestri Di Kabupaten Gowa Provinsi Sulawesi Selatan. Jurnal Hutan Dan Masyarakat. 2019; 11(2): 126. Publisher Full Text\n\nSaraswati Y, Dharmawan AH: Resiliensi Nafkah Rumahtangga Petani Hutan. Jurnal Sosiologi Pedesaaan. 2014; 02(01): 63–75.\n\nSchrover M: Migration histories.Scholten P, editor. Introduction to migration studies (IMISCOE Re). Springer; 2022; pp. 25–46. Publisher Full Text\n\nSchrover M, Moloney DM: Gender, Migration and Categorisation: Making Distinctions between Migrants in Western Countries, 1945-2010. Amsterdam University Press; 2013.\n\nSharafi K, Pirsaheb M, Maleki S, et al.: Knowledge, attitude and practices of farmers about pesticide use, risks, and wastes; a cross-sectional study (Kermanshah, Iran). Science of The Total Environment. 2018; 645: 509–517. Publisher Full Text\n\nShen J, Chanda A, D’Netto B, et al.: Managing diversity through human resource management: an international perspective and conceptual framework. The International Journal of Human Resource Management. 2009; 20(2): 235–251. Publisher Full Text\n\nSimbolon NRB, Sihombing M, Kusmanto H, et al.: Implementasi Program Kartu Indonesia Sehat Implementation of the Indonesia Healthy Card Program. Strukturasi: Jurnal Ilmiah Magister Administrasi Publik. 2019; 1(2): 147–155. Publisher Full Text\n\nSmith J: Sharing Financial Responsibilities: A Study of Cooperative Budgeting in Dual-Income Families. Journal of Family Economics. 2019; 35(2): 145–162.\n\nSobczak-Szelc K, Fekih N: Migration as one of several adaptation strategies for environmental limitations in Tunisia: evidence from El Faouar. Comparative Migration Studies. 2020; 8(1): 8. Publisher Full Text\n\nSumersi R, Rahmadani S, Akbar WK: Perubahan Sosial Ekonomi Dan Strategi Nafkah Rumah Tangga (Studi Kasus Covid-19 Dinagari Silaut Kecematan Silaut Kabupaten Pesisir Selatan). Jurnal Pendidikan Tambusai. 2021; 5: 6070–6076.\n\nTacoli C: Understanding the opportunities and constraints for low-income groups in the peri-urban interface: the contribution of livelihood frameworks. Strategic Environmental Planning and Management for the Peri-urban Interface Research Project.1999.\n\nTrihastono I, Marwiyanto J, Ristiono E, et al.: Analisa Gini Rasio Kota Yogyakarta 2020. Dinas Komunikasi Informatika dan Persandian.2021.\n\nUN-Habitat: The Challenge of Slums: Global Report on Human Settlements 2003.2003.\n\nVijayalakshmi A, Dev P, Kulkarni V: Domestic workers and sexual harassment in India: Examining preferred response strategies. World Dev. 2022; 155: 105875. Publisher Full Text\n\nWijaya K, Syairozi MI: Analisis perpindahan tenaga kerja informal Kabupaten Pasuruan. Jurnal Paradigma Ekonomika. 2020; 15(2): 173–182. Publisher Full Text\n\nWorld Bank: Agriculture for Development. World Development Report 2008.2007.\n\nWorld Health Organization: The World Health Report 2008: Primary Health Care Now More Than Ever.2008.\n\nWidyaningsih TS: Figure and dataset of Household Resilience of Women Migrant Workers Sellers of Jamu Gendong. figshare. [Dataset]. Figure. 2023. Publisher Full Text\n\nWulandari RA, Azrianingsih R: Etnobotani Jamu Gendong Berdasarkan Persepsi Produsen Jamu Gendong di Desa Karangrejo, Kecamatan Kromengan, Kabupaten Malang. Jurnal Biotropika. 2014; 2(4)."
}
|
[
{
"id": "309665",
"date": "23 Aug 2024",
"name": "Md Imran Khan",
"expertise": [
"Reviewer Expertise I have observed overall aspect of the study. seem to be good. Need some changes"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper deals with an important area of research but needs some improvement to maintain the quality of work in this journal. 1. The author should indicate the research problem and research questions in the methodology section. 2. How this study contributes to the existing literature. Explain in the discussion section and abstract. 3. The author has used the snowball sampling technique to collect the primary data, Explain in the methodology section how the result of this study is unbiased.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12635",
"date": "29 Oct 2024",
"name": "Ary Widiyanto",
"role": "Author Response",
"response": "The author should indicate the methodology section's research problem and questions. Respond: Research problems and research questions have been added to the manuscript (page 4) Research problems Despite the importance of women's migration and their role in the informal sector, such as selling herbal medicine, for the economic sustainability of families and communities, the current literature tends to focus on men's migration. As a result, essential aspects of women's migration, including livelihood strategies, socio-economic resilience, and the influence of local social and cultural capital on migrant women's economic resilience, have not received adequate attention. Furthermore, there is still a lack of research on how migrant women in the informal sector, such as herbal medicine sellers, develop resilience strategies and use different forms of capital to survive in urban areas. Research Questions 1.What strategies are used by migrant women who sell herbal medicine in urban areas to defend their lives and those of their families? 2.Which types of capital (human, physical, social, natural, and financial) are employed by migrant women who sell herbal medicine to help them maintain their economic resilience? 3.How do social capital and local cultural values influence migrants' livelihood strategies and financial security in the informal sector? How this study contributes to the existing literature. Explain in the discussion section and abstract. Respond: The ways to contribute to the literature were added in discussions and in the abstract. Page 10 (Economic resilience is not solely based on material resources, but also on the cultural values that the community adheres to) Page 11 (This study found that migrant women can exit from the limitation of financial capital by employing human capital, such as the skill to make jamu, physical capital, such as access to facilities and infrastructures, and social capital that links to other jamu sellers) Page 11 (This study provides a new perspective about business diversification in the informal sector (jamu gendong) and also adds insight into the livelihood strategies used by herbal medicine sellers to survive in difficult situations). The author has used the snowball sampling technique to collect the primary data, Explain in the methodology section how the result of this study is unbiased Respond: The steps to avoid bias of snowball sampling have been explained in the methodology section. More detail is showed in the manuscript (page 5)"
}
]
},
{
"id": "326877",
"date": "03 Oct 2024",
"name": "Benni Hasbiyalloh",
"expertise": [
"Reviewer Expertise Migration Studies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nWhile the study tackles an important and underexplored area of migration and gendered resilience, there are key aspects where the article could be improved for clarity, depth, and overall rigor.\n\nConceptual and Theoretical Gaps\nDifferentiation of Migration Types: While the article introduces migration as a concept, it lacks a nuanced discussion of different types, such as circular, temporary, and permanent migration, which are crucial for understanding the mobility patterns and livelihood strategies of the jamu gendong sellers. Including these distinctions would provide greater conceptual clarity and strengthen the study’s theoretical grounding. Coherence Between Theories and Analysis: The article mentions multiple theories and concepts (e.g., resilience, livelihood strategies, gender dynamics), but their connections to each other and to the findings are not always rigorously made. A clear conceptual framework outlining how these theories interlink and how they guide the analysis would enhance the study’s theoretical depth\n\nIntegration of Gendered Dynamics\nWhile the study focuses on women’s experiences in migration, the gendered aspects of resilience and economic roles are not sufficiently explored. A more thorough integration of a gender lens—examining how gender influences resilience strategies, social capital formation, and migration decisions—would provide a deeper understanding of the specific challenges and adaptations of female migrant workers.\n\nMethods and Reproducibility Issues\nDetails on Sampling and Analysis Procedures: The article briefly describes using snowball sampling for both questionnaires and in-depth interviews, but further details on the selection criteria, diversity of respondents, and the flow of data collection would improve reproducibility. For instance, clarifying how initial participants were identified and ensuring diverse representation would strengthen the methodological rigor. Quantitative Sampling: The use of snowball sampling for the 51 participants is noted, but further details would improve replicability. For instance:\nHow was the initial participant identified? Were any inclusion/exclusion criteria besides having two years of experience applied? Were any efforts made to ensure diverse representation (e.g., in terms of age, socioeconomic status)?\n\nQualitative Sampling: Six informants were selected from technical agencies, but the rationale for their selection is unclear. Provide more details on:\nThe specific criteria used to choose these informants. How the snowball technique was applied in practice for the qualitative interviews.\n\nWhile the HRI is explained, the exact process for scoring responses and interpreting results could be made clearer. Suggestions include:\nProviding examples of how indicators are scored and weighted. Explaining how the categories (0-30, 31-60, etc.) were developed and any theoretical or empirical basis for these thresholds.\n\nData Presentation and Analysis\nThe results are predominantly descriptive and do not always effectively link back to the theoretical framework. To provide a more robust analysis, findings should be clearly tied to the concepts of resilience, livelihood capital, and migration strategies, with discussions highlighting how empirical results support or contrast with existing literature. The HRI is a potentially powerful tool for assessing household resilience, but its application is not clearly explained. For example, a step-by-step outline of how HRI scores were calculated and how households were categorized into resilience categories would greatly enhance understanding and enable other researchers to replicate the methodology.\n\nStrengthening the Conclusions and Recommendations\nThe conclusions generally align with the findings but could be strengthened by explicitly stating how they address the research objectives outlined in the introduction. Additionally, the recommendations for practice—such as training and capacity-building for jamu sellers—should be tied directly to the study’s findings to ensure they are contextually relevant and actionable. Highlighting the study’s unique contributions to the field (e.g., by emphasizing the gendered dimensions of informal migration and resilience) would provide a more compelling case for the significance of the research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12634",
"date": "29 Oct 2024",
"name": "Ary Widiyanto",
"role": "Author Response",
"response": "Article introduces migration as a concept, it lacks a nuanced discussion of different types, such as circular, temporary, and permanent migration article introduces migration as a concept, it lacks a nuanced discussion of different types, such as circular, temporary, and permanent migration. Respond: This has been added in the introduction section (page 2) This is known as circular migration, repeated, where herbal medicine sellers will return to their place of origin after temporarily living at their destination (Skeldon, 2012). Herbal medicine sellers in Ciamis frequently perform this type of migration. However, some individuals carry out a temporary migration, namely moving for a certain period. After reaching their goal, they will return to their place of origin. Furthermore, permanent migration means moving to settle permanently in the destination. The last two models occur if the Jamu Gendong seller marries a resident. Coherence between theory and analysis & examining how gender influences resilience strategies, social capital formation, and migration decisions Respond: This has been added in the discussion section (page 11) . This study found that migrant women can exit from the limitation of financial capital by employing human capital, such as the skill to make jamu, physical capital, such as access to facilities and infrastructures, and social capital that links to other jamu sellers. The women who sell jamu gendong in categories 2 and 3 have shown a capacity to handle their livelihood with resilience. Resilience is a significant factor in shaping the livelihood strategies of women selling jamu gendong, often limited by gender dynamics (Tanner et al., 2022). Despite facing social and economic difficulties, women selling jamu gendong have demonstrated the ability to adapt and innovate their livelihood strategies, discovering ways to support their families. Women who sell jamu gendong have shown the capacity to empower themselves and disrupt traditional gender norms by implementing livelihood strategies, leading to fairer gender dynamics and more resilient future generations. The gender norm that women are sufficient to be housewives while household economics are the husband's responsibility (Happel & Becker, 1983), does not apply. Besides, men may have greater access to resources for long-distance migration or employment opportunities outside their immediate communities, whereas women’s networks may focus more on local support and survival strategies (Rica, 2008). This cyclical relationship demonstrates how resilient and livelihood strategies can gradually alter gender roles, resulting in sustainable development and gender equality."
}
]
}
] | 1
|
https://f1000research.com/articles/13-25
|
https://f1000research.com/articles/13-1413/v1
|
22 Nov 24
|
{
"type": "Study Protocol",
"title": "Protocol for Conducting Scoping Review on Reliability and Validity of Low-Stakes Assessments in Medical Education",
"authors": [
"Imran Zafar",
"Susan Waller",
"Lambert Schuwirth",
"Carvalho Filho",
"Mohi Eldin Magzoub",
"Imran Zafar",
"Susan Waller",
"Lambert Schuwirth",
"Carvalho Filho"
],
"abstract": "Low-stakes assessments (LSAs) are widely used in medical education to promote continuous learning by providing formative feedback and minimizing the high-stress environment associated with high-stakes assessments. While LSAs are recognized for their role in supporting student learning, questions remain about their reliability and validity. This scoping review aims to systematically identify and synthesize existing literature on the reliability and validity of LSAs within medical education contexts. This study aims to map the methodologies used to establish psychometric parameters, identify problems, and offer best practices. The review will use the Joanna Briggs Institute methodology, encompassing a comprehensive search across six academic databases and grey literature to identify relevant studies published from 2000 onward. Two reviewers will independently screen and extract data, using the Covidence tool for systematic screening and data extraction. Data will be analyzed using qualitative and quantitative approaches to provide an overview of reliability and validity evidence for LSAs in medical education. Insights into motivational and psychometric theories, such as Self-Determination Theory, Classical Test Theory, and Generalizability Theory, that inform LSA design and implementation will be used to analyse the findings in this review. Expected outcomes include a detailed map of the literature on LSA reliability and validity, identification of key challenges, theoretical underpinnings and recommended strategies for improving LSA practices in medical education. Findings will inform future research and provide guidelines for optimizing the use of LSAs to enhance student learning outcomes, assessment integrity, and the educational experience in medical training.",
"keywords": [
"Low-stakes assessment",
"validity",
"reliability"
],
"content": "Rationale and background\n\nLow-Stakes Assessments (LSAs) in medical education are essential tools that support continuous learning by providing formative feedback and monitoring student progress. These assessments are designed to minimize the anxiety and pressure often associated with high-stakes evaluations, thereby creating an environment conducive to authentic learning and self-regulation. The reliability of LSAs is grounded in their ability to consistently provide accurate feedback that reflects students’ actual learning and competencies, while their validity is ensured by aligning the assessments closely with educational objectives and learning outcomes (Schut et al., 2018).\n\nOne of the key strengths of LSAs is their capacity to foster a continuous flow of information, allowing learners to self-regulate their learning effectively. Schut et al. (2018), emphasized that the formative nature of these assessments enhances their validity by ensuring that the feedback provided is relevant and actionable. Reduced stakes associated with these assessments contribute to their reliability, as they encourage more authentic student engagement and reduce test anxiety, leading to more accurate assessments of student knowledge and skills (Ganesan et al., 2023).\n\nThe design of LSAs also supports the provision of honest and constructive feedback, which is crucial for maintaining the validity of the assessment process. It is argued that using multiple LSAs throughout the educational process allows for a more comprehensive evaluation of student performance, thereby increasing the reliability of the overall assessment system (Schut et al., 2020). This approach mitigates the risk of a single assessment unduly influencing final outcomes, ensuring that students are evaluated based on a broader and more representative sample of their abilities.\n\nDespite the benefits, challenges remain in ensuring the reliability and validity of LSAs. Factors such as student motivation and the novelty of assessment formats can impact performance, affecting the reliability of these assessments (Madrazo et al., 2018). Research by Silm et al. (2013) and Knekta & Eklöf (2015) highlights the importance of understanding test-taker motivation to maintain both the reliability and validity of LSAs, particularly in medical education, where consistent and accurate assessment of competencies is critical.\n\n\nWhat are the types of low-stakes assessment in medical education?\n\nLSAs in medical education encompass a variety of formats and methodologies designed to facilitate learning and provide feedback without the high-pressure consequences associated with traditional high-stakes assessments. These assessments are integral to fostering a supportive educational environment and can take several forms, each serving distinct purposes in the learning process.\n\n1. Formative Assessments: These assessments are designed to monitor student learning and provide ongoing feedback that can be used by instructors to improve their teaching and by students to enhance their learning. Formative assessments, particularly when they are low-stakes, create opportunities for self-regulation and continuous improvement among learners (Schut et al., 2020). Examples of LSAs in this category include quizzes, practice exams, and informal assessments during clinical rotations.\n\n2. Objective Structured Clinical Examinations (OSCEs): While OSCEs can be high-stakes, they are often utilized in a low-stakes format to assess clinical skills in a supportive environment. Low-stakes OSCEs can help students gauge their competencies and identify areas for improvement without the pressure of high-stakes evaluations (Madrazo et al., 2018). This format allows for practical skill assessment in a controlled setting, promoting learning through practice.\n\n3. Peer Assessments: Peer evaluations can give and receive feedback between peers. This method encourages collaborative learning and reflection. Peer assessments can motivate students and enhance their learning experience in low-stakes contexts (Schüttpelz-Brauns et al., 2020).\n\n4. Self-Assessments: Self-assessment tools enable students to evaluate their own knowledge and skills, fostering a sense of ownership over their learning. These assessments can help identify gaps in knowledge and encourage students to take proactive steps toward improvement. Self-regulated learning is significantly influenced by the stakes associated with assessments (Ganesan et al., 2023).\n\n5. Progress Committees: The use of progress committees introduces an independent third party into the assessment process, allowing for a more holistic view of a student’s progress over time. This approach can help mitigate the pressure associated with individual assessments and provide a supportive framework for student development (Schut et al., 2020).\n\n6. Reflective Journals: Encouraging students to maintain reflective journals can promote critical thinking and self-reflection. This method allows students to document their learning experiences, challenges, and growth throughout their medical education journey (Paloniemi et al., 2024).\n\n7. Quizzes and Short Tests: Frequent low-stakes quizzes can help reinforce learning and provide immediate feedback. These assessments can be administered in various formats, such as online quizzes or in-class tests, and are designed to assess knowledge retention and understanding of key concepts (Bains et al., 2023).\n\n\nImportance of reliability and validity\n\nThe reliability and validity of LSAs are critical in ensuring that these assessments accurately reflect student abilities and knowledge. Reliable assessments consistently yield the same results under similar conditions, while valid assessments accurately measure what they are intended to measure. Without these qualities, LSAs cannot effectively inform educational decisions or contribute to meaningful learning.\n\nThe importance of reliability and validity in LSAs within medical education cannot be overstated.\n\nReliability in low-stakes assessments is essential for maintaining the integrity of the evaluation process. According to Schut et al., reliable assessments provide consistent results across different contexts and times, which is particularly important in medical education where competencies must be accurately gauged to ensure patient safety and effective care (Schut et al., 2020). These assessments, while designed to be less stressful for students, still require rigorous standards to ensure that they effectively measure the competencies and knowledge of learners. Both reliability and validity are crucial for ensuring that LSAs contribute positively to the educational process.\n\nReliable LSAs can help educators identify areas where students may need additional support, thereby enhancing the overall learning experience (Schüttpelz-Brauns et al., 2020). The reliability of assessment tools can be bolstered through careful design and the use of multiple assessors, in a programmatic approach that incorporates various low-stakes assessments to provide a more comprehensive evaluation of student performance (Schut et al., 2020).\n\nValidity, on the other hand, ensures that the assessments are measuring the intended constructs. The necessity of establishing validity evidence for assessment tools in medical education is integral to ensuring that the results of these assessments accurately reflect student competencies (Hoover et al., 2013). This is particularly relevant in LSAs, where the goal is to foster learning rather than merely to evaluate.\n\nThe interplay between reliability and validity is critical. If an assessment is not reliable, it cannot be valid and inconsistent results undermine the credibility of the assessment process.\n\n\nTheoretical framework for assessing the reliability and validity\n\nThe theoretical framework for assessing the reliability and validity of LSAs in medical education is multifaceted and encompasses several psychometric theories and motivational frameworks. It emphasizes the importance of structured assessment frameworks that align with educational outcomes, thereby enhancing the reliability and validity of the assessments used (Pearce et al., 2015). The concept of validity in medical education has evolved, necessitating a consensus on its definition and application within assessments (Royal, 2017). This is particularly relevant for LSAs, which often face challenges related to students’ test-taking behaviors and motivation (Royal, 2017). Strategies that promote serious engagement, such as mentorship discussions and clear consequences for non-participation, can enhance the effectiveness of these assessments (Royal, 2017). Thus, integrating these elements into a cohesive framework can significantly improve the quality and impact of low-stakes assessments in medical education (Schuwirth et al., 2022).\n\n\nKey theories in assessment\n\nUnderstanding student motivation is crucial for enhancing the effectiveness of LSAs. The following theories provide insights into how to increase student engagement and effort during these assessments:\n\n1. Self-Determination Theory (SDT) emphasizes the role of intrinsic motivation and the need for autonomy, competence, and relatedness. Strategies derived from SDT, such as providing feedback and discussing performance with mentors, have been shown to increase the seriousness with which students approach LSAs (Deci & Ryan, 1985; El Boghdady & Alijani, 2017).\n\n2. Expectancy-Value Theory posits that students’ motivation is influenced by their expectations of success and the value they place on the task. Incorporating elements that enhance the perceived value of LSAs can lead to increased engagement and effort from students (Schüttpelz-Brauns et al., 2018).\n\n\n\n1. Classical Test Theory (CTT) focuses on the reliability of test scores, emphasizing the consistency of measurements across different instances. In CTT, observed scores are composed of true scores and measurement error, making it crucial for ensuring that LSAs yield reliable results(Schuwirth & van der Vleuten, 2011).\n\n2. Generalizability Theory (GT) extends CTT by examining how various sources of error affect test scores. GT allows for a more nuanced understanding of reliability by considering multiple facets of measurement, such as different raters or test forms, which is particularly relevant in LSAs where variability in student engagement can influence results (Schuwirth & van der Vleuten, 2011). G-Theory can be applied to performance-based assessments, allowing educators to evaluate the reliability of their assessments more rigorously (Peeters, 2021). This approach can help identify areas for improvement in assessment design and implementation.\n\n3. Item Response Theory (IRT) analyzes the relationship between an individual’s latent traits (abilities) and their item responses. It is beneficial for developing assessments that can adapt to different levels of student ability, thereby enhancing the validity of low-stakes assessments by ensuring they accurately reflect student knowledge (Schuwirth & van der Vleuten, 2011).\n\n4. Validity Theory: Validity encompasses the degree to which an assessment measures what it is intended to measure. The framework for establishing validity can be based on the five sources of validity evidence proposed by the Standards for Educational and Psychological Testing. These sources include content validity, criterion-related validity, construct validity, consequential validity, and face validity, providing preliminary validity evidence for LSAs, particularly in clinical settings, ensuring assessments accurately reflect the competencies being measured (Sireci & Rodriguez, 2022). This evidence is critical for building trust in the assessment process among students and educators alike.\n\n5. Programmatic Assessment: The concept of programmatic assessment integrates multiple assessment methods to provide a comprehensive evaluation of student competencies. Multiple LSAs, especially those without numerical grades, can enhance the reliability and validity of the assessment process (Schut et al., 2020). This approach allows for a more holistic view of student performance and encourages continuous feedback, which is essential for fostering a learning-oriented environment.\n\n6. Feedback and Learning Theory: The role of feedback in the assessment process is crucial for enhancing learning outcomes. There is a catalytic effect of assessment, where feedback generated from assessments leads to improved learning and competency development (Heeneman et al., 2015) This aligns with the principles of formative assessment, which emphasize the importance of using assessment as a tool for learning rather than merely of learning.\n\n7. Psychometric principles are vital for ensuring the reliability and validity of LSAs. These include the careful design of assessment items, the training of raters, and the use of statistical methods to analyze assessment data. In simulation-based assessments rater training has been shown to enhance both reliability and validity (Mackenzie et al., 2023). Ensuring that raters are well-trained can mitigate biases and improve the consistency of assessment outcomes.\n\n8. Student Perceptions and Motivation: The perceptions of students regarding the stakes of assessments can significantly influence their engagement and performance (Schut et al., 2018). Understanding the psychological dynamics at play can help educators design assessments that motivate students and encourage genuine learning.\n\nElements of the above theories will be applied to examine how various factors, such as item design, scoring methods, and test administration conditions, influence the reliability and validity of LSAs. The review will particularly consider how the principles of CTT and IRT can be adapted to the unique context of LSAs in medical education.\n\n\nMethods\n\nThe review will use the Joanna Briggs Institute’s framework for scoping review studies, searching six databases and grey literature. A presearch will be done in PubMed, Scopus, and Google Scholar using terms related to LSAs, formative assessment, continuous assessment, and programmatic assessment within the context of medical education. The Covidence Systematic Review tool will aid in screening and conflict resolution.\n\nThe reference lists of included studies will be checked manually for other relevant literature. Two research team members will independently screen and extract data, resolving discrepancies with a third team member. Inclusion and exclusion criteria will be refined iteratively based on key research themes.\n\nData will be qualitatively and quantitatively analyzed and presented in diagrams or tables with a narrative synthesis. The synthesis will map data related to low-stakes assessment in medical education, identify challenges and opportunities of this assessment approach. The review will follow PRISMA guidelines, focusing on the reliability and validity of the LSAs in medical education.\n\n\n\n— What are the most used methods for establishing the reliability and validity of LSAs in medical education?\n\n— How do different factors, such as test format, item type, and scoring procedures, affect the reliability and validity of LSAs?\n\n— What are the challenges in maintaining reliability and validity in low-stakes assessments, and how are these challenges addressed in the literature?\n\n— What best practices are recommended for enhancing the reliability and validity of LSAs in medical education?\n\n— What are the underpinning theories, frameworks or models cited in the literature which support the reliability and validity of LSAs?\n\nInclusion criteria:\n\n1. Topic: The study must primarily focus on LSAs’ reliability and validity in medical education.\n\n2. Study Population: Participants should include medical students, interns, or residents (junior doctors in training) completing LSAs.\n\n3. Assessment Type: Assessments must be low-stakes, meaning they do not significantly affect final grades or academic standing.\n\n4. Publication Date: Only studies published after January 2000 will be considered.\n\n5. Language: Studies must be published in English.\n\n6. Methodology: Studies employing quantitative, qualitative, or mixed-methods approaches are eligible.\n\nExclusion criteria:\n\n1. High-Stakes Assessments: Studies focused on high-stakes assessments that significantly impact grades or academic standing will be excluded.\n\n2. Non-Medical Education: Studies from non-medical education settings or involving non-medical students will be excluded.\n\n3. Non-English Language: Studies not published in English will be excluded.\n\n4. Non-Primary Focus on Reliability and Validity: Studies that do not explicitly investigate LSAs’ reliability and validity will be excluded.\n\n5. Pre-2000 Publications: Studies published or grey literature dated before 2000 will not be included.\n\nThe review will consider a wide range of study types, including quantitative research (e.g., randomized controlled trials, quasi-experimental studies, cohort studies, cross-sectional studies, and pre-post studies), qualitative research (e.g., interviews, focus groups, and case studies), and mixed-methods studies that combine both data types. Systematic reviews, meta-analyses, and surveys will also be included to capture broader trends, summarize existing research, and highlight gaps.\n\nThis scoping review will adhere to the Joanna Briggs Institute (JBI) methodology, specifically utilizing the PCC framework (Population, Concept, and Context) to clearly define the review’s focus. In line with the JBI Scoping Review checklist, the review will incorporate these elements explicitly to ensure comprehensive coverage and alignment with the protocol requirements. Additionally, the review will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The planned start date for this review is December 2024, with an expected completion date in March 2025.\n\nThe review will search six key databases, including PubMed, MEDLINE, ERIC, PsycINFO, Scopus, and Web of Science.\n\nA detailed search strategy will be developed with the guidance of a medical librarian, using a combination of keywords and Medical Subject Headings (MeSH) terms relevant to LSAs, student learning, and medical education. Boolean operators (AND, OR, NOT) will be used to refine the search results.\n\nAn initial screening of titles and abstracts will be conducted by two independent reviewers to identify studies that meet the inclusion criteria. Studies passing this screening will undergo a full-text review to confirm their relevance.\n\nData extraction will be conducted using a standardized form to systematically capture essential information from each included study. This form will record details such as study title, authors, publication year, objectives, study design, theoretical framework, participant characteristics, types of low-stakes assessments (LSAs) used, outcome measures related to student learning, and key findings. To ensure accuracy, two reviewers will independently extract data, resolving any discrepancies through discussion or, if needed, consultation with a third reviewer. Extracted data will be presented in a summary table and accompanied by a narrative explanation.\n\n\n\n— A comprehensive map of the current literature on the reliability and validity of LSAs in medical education.\n\n— Identification of common challenges and effective strategies for enhancing reliability and validity in LSAs.\n\n— Recommendations for future research directions related to the validity and reliability of LSAs, based on identified gaps.\n\n— Underpinning theories associated with reliability and validity of LSAs.\n\n\nEthics and dissemination\n\nAs this review will involve only published, and grey literature, no ethical approval is required. Findings will be disseminated through academic conferences and publications in peer-reviewed journals.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\nRepository: PRISMA-P checklist for ‘Protocol for conducting scoping review on reliability and validity of low-stakes assessments in medical education’. DOI: 10.6084/m9.figshare.27627834.v2 (Zafar et al., 2024).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors would like to thank the support staff and colleagues who provided insight and expertise that greatly assisted the research, as well as the library services for assistance with the literature search.\n\n\nReferences\n\nBains M, Goei K, Kaliski D: Implementation and effects of low stakes quiz feedback on exam performance in a health professional program. Physiology. 2023; 38(S1). Publisher Full Text\n\nDeci EL, Ryan RM: Intrinsic Motivation and Self-Determination in Human Behavior. US: Springer; 1985. Publisher Full Text\n\nEl Boghdady M, Alijani A: Feedback in surgical education. Surgeon. 2017; 15(2): 98–103. Publisher Full Text\n\nGanesan I, Cham B, Teunissen PW, et al.: Stakes of Assessments in Residency: Influence on Previous and Current Self-Regulated Learning and Co-Regulated Learning in Early Career Specialists. Perspect. Med. Educ. 2023; 12(1): 237–246. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeeneman S, Oudkerk Pool A, Schuwirth LWT, et al.: The impact of programmatic assessment on student learning: theory versus practice. Med. Educ. 2015; 49(5): 487–498. PubMed Abstract | Publisher Full Text\n\nHoover MJ, Jung R, Jacobs DM, et al.: Educational Testing Validity and Reliability in Pharmacy and Medical Education Literature. Am. J. Pharm. Educ. 2013; 77(10): 213. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKnekta E, Eklöf H: Modeling the Test-Taking Motivation Construct Through Investigation of Psychometric Properties of an Expectancy-Value-Based Questionnaire. J. Psychoeduc. Assess. 2015; 33(7): 662–673. Publisher Full Text\n\nMackenzie MJ, Hagel C, Lin Y, et al.: The Reliability of the Resuscitation Assessment Tool (RAT) in Assessing Emergency Medicine Resident Competence in Pediatric Resuscitation Scenarios: A Prospective Observational Pilot Study. Cureus. 2023; 15: e35869. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMadrazo L, Lee CB, McConnell M, et al.: Self-assessment differences between genders in a low-stakes objective structured clinical examination (OSCE). BMC. Res. Notes. 2018; 11(1): 393. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPaloniemi E, Hagnäs M, Mikkola I, et al.: Reflective capacity and context of reflections: qualitative study of second-year medical students’ learning diaries related to a general practice course. BMC Med. Educ. 2024; 24(1): 222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPearce J, Edwards D, Fraillon J, et al.: The rationale for and use of assessment frameworks: improving assessment and reporting quality in medical education. Perspect. Med. Educ. 2015; 4(3): 110–118. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeeters M: Moving beyond Cronbach’s Alpha and Inter-Rater Reliability: A Primer on Generalizability Theory for Pharmacy Education. Innov. Pharm. 2021; 12(1): 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoyal K: Four tenets of modern validity theory for medical education assessment and evaluation. Adv. Med. Educ. Pract. 2017; 8: 567–570. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchut S, Driessen E, van Tartwijk J , et al.: Stakes in the eye of the beholder: an international study of learners’ perceptions within programmatic assessment. Med. Educ. 2018; 52(6): 654–663. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchut S, Heeneman S, Bierer B, et al.: Between trust and control: Teachers’ assessment conceptualisations within programmatic assessment. Med. Educ. 2020; 54(6): 528–537. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchüttpelz-Brauns K, Hecht M, Hardt K, et al.: Institutional strategies related to test-taking behavior in low stakes assessment. Adv. Health Sci. Educ. 2020; 25(2): 321–335. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchüttpelz-Brauns K, Kadmon M, Kiessling C, et al.: Identifying low test-taking effort during low-stakes tests with the new Test-taking Effort Short Scale (TESS) – development and psychometrics. BMC Med. Educ. 2018; 18(1): 101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchuwirth L, Colliver J, Gruppen L, et al.: Research on Assessment Practices. International Best Practices for Evaluation in the Health Professions. CRC Press; 2022; pp. 59–75. Publisher Full Text\n\nSchuwirth LWT, van der Vleuten CPM : General overview of the theories used in assessment: AMEE Guide No. 57. Med. Teach. 2011; 33(10): 783–797. PubMed Abstract | Publisher Full Text\n\nSilm G, Must O, Täht K: TEST-TAKING EFFORT AS A PREDICTOR OF PERFORMANCE IN LOW-STAKES TESTS. Trames - J. Humanit. Soc. Sci. 2013; 17(4): 433. Publisher Full Text\n\nSireci SG, Rodriguez G: Validity in Educational Testing. Validity in Educational Testing. Routledge; 2022. Publisher Full Text\n\nZafar I, Waller SA, Schuwirth L, et al.: Protocol for conducting scoping review on reliability and validity of low-stakes assessments in medical education. figshare. Journal contribution. 2024. Publisher Full Text"
}
|
[
{
"id": "355767",
"date": "20 Jan 2025",
"name": "Eva Mukurunge",
"expertise": [
"Reviewer Expertise Assessment in Medical education",
"Communication in Medical Education"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nA well written protocol for an essential study in assessment in Medical education. You need to revise your list of types of Low-Stakes Assessments (LSAs) in the view that assessments are generally either formative or summative. You have listed formative assessments as an example of LSAs which then limits your list since all LSAs fall under formative assessments. In order to clear the confusion, a definition of what you are referring to as LSAs would be essential. Your list of LSAs includes Progress Committees, which should rather be mentioned as quality assurance checks in the implementation of LSAs.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1413
|
https://f1000research.com/articles/13-1412/v1
|
22 Nov 24
|
{
"type": "Case Report",
"title": "Case Report: Case report: Hepatic and pulmonary echinococcosis with reactivated tuberculosis",
"authors": [
"Yousif Mohamed",
"Sohaib Arbab",
"Ali Mohamed",
"Sohaib Arbab",
"Ali Mohamed"
],
"abstract": "The co-infection of Pulmonary Tuberculosis (TB) and hydatid disease is rare. Diagnosis and treatment of this co-infection may be challenging as both diseases present with overlapping clinical manifestations, especially in war zones where the health system is destroyed. We are reporting a 45-year-old female police officer transferred to Sinnar Sudan due to ongoing conflict. She was admitted with chronic cough, shortness of breath, and weight loss. The preliminary diagnosis of pulmonary TB was made based on chest X-ray examination and sputum analysis. Further imaging showed cystic lesions in both the liver and the lungs, and thus a diagnosis of Echinococcosis was made. Surgical intervention was done successfully followed by the courses of Albendazole and anti-TB medication. The clinical condition of the patient improved, with the disappearance of all symptoms. This case represents the diagnostic dilemma of dual infections in the areas of their endemicity because of the symptomatology overlap that might occur and result in an erroneous diagnosis. It does demand an appropriate diagnostic approach, thus, with advanced imaging applications, and once more, emphasizes the interdisciplinary attitude in its treatment for the best possible result.",
"keywords": [
"Echinococcosis",
"Tuberculosis",
"Co-infection",
"Hepatic cysts",
"Pulmonary cysts",
"Reactivation."
],
"content": "Introduction\n\nEchinococcosis is a disease that primarily affects developing nations with poor medical infrastructure, where cohabitation with domesticated animals is common.1 It poses distinct difficulties because of the complicated nature of its diagnosis and treatment; moreover, it can metastasize similarly to cancer due to its elevated recurrence rate after therapy.2\n\nThe simultaneous presence of tuberculosis (TB) and hydatid disease in a person with a healthy immune system is a very uncommon situation. Due to the overlapping symptoms and complications associated with both conditions, accurately diagnosing individuals who are coinfected can be challenging.3 Many factors may influence the co-infection of TB and parasitic diseases, including sociodemographic factors related to gender and age, underlying diseases, and residency in co-endemic areas with a higher prevalence of M. tuberculosis and parasitic infection.4 Further research into the immunological interactions between the two diseases is needed, with the hope of improving therapeutic strategies.\n\n\nCase report\n\nDue to the conflict in Khartoum, a 45-year-old woman was compelled to relocate to Sinnar, Sudan, an area known for its abundance of domestic animals such as sheep, dogs, and goats. After two months of residence, she began experiencing symptoms of shortness of breath, chronic cough, and weight loss. The patient presented with fever and was found to have an erythrocyte sedimentation rate of 130 mm per hour, a C-reactive protein level of 88 mg per liter, and a white blood cell count of 33750 per cubic millimeter with 88% neutrophils (Table 1). A lung abscess was detected on her chest X-ray, leading to empyema, pneumothorax, and pleural effusion in the right lung (Figure 1A). Additionally, an unidentified round-shaped lesion was observed in the left lung (Figure 1A). Due to the limited resources in the area, including a lack of radiologists, technicians, and reliable power supply, physicians diagnosed the patient clinically with pulmonary tuberculosis and this was further confirmed by sputum analysis yielding acid fast bacilli. The appropriate treatment was initiated, including intravenous antibiotics and chest tube insertion for draining the empyema. She was discharged with anti-tuberculous medication and advised to return for a follow-up in two weeks.\n\nThe patient was readmitted due to upper abdominal fullness and a palpable mass in the liver. Abdominopelvic ultrasound indicated the presence of a cystic lesion in the left liver lobe, which was further confirmed by computed tomography showing a solitary thin-walled cystic lesion at segments two and four (Figure 1B). Evaluation of chest Computed tomography (CT) revealed loculated pneumothorax, round lung collapse, and adjacent pleural thickening (Figure 1C). A test using enzyme-linked immunosorbent assay revealed an anti-echinococcus IgG antibody index of 16.8 in the patient’s serum supporting the diagnosis of Echinococcosis, as well as reactivation of pulmonary Tuberculosis. The patient responded well to Albendazole treatment, and her symptoms resolved. Surgical intervention was done, and a follow-up ultrasound sound showed no signs of recurrence. The possibility of pleural decortication was considered to facilitate lung re-expansion.\n\n\nDiscussion\n\nWe reported a case of co-infection with Echinococcosis and TB, this combination of Echinococcosis and reactivated TB is definitely a diagnostic challenge and requires comprehensive diagnostic strategies in endemic areas.5 Overlapping clinical manifestations include cough and systemic symptoms which would render the differential diagnosis very extensive with the aid of imaging and microbiological investigations.6 Immunosuppressive effects due to parasitic infections are one of the predisposing factors for the reactivation of TB.7 Patients with risk factors for immunodeficiency conditions or those taking immunosuppressive drugs have a greater risk of opportunistic infection or coexistence. Co-infections should always be considered by physicians and investigated in those whose symptoms are resistant to treatment.4\n\nMany Civilians in Sudan suffer from malnutrition due to the ongoing war there which started in 2023, malnutrition heightens the likelihood of contracting tuberculosis (TB) and can lead to the reactivation of dormant pulmonary TB. Conversely, TB is known to contribute to malnutrition. Assessing the nutritional health and anemia of patients with active tuberculosis is a crucial aspect of managing the disease.8\n\nTreatment should be done for both the infections simultaneously, keeping drug interactions and their adverse effects in mind: Albendazole-a benzimidazole acting against Echinococcosis9 and standard ATT given for TB. Monitoring for hepatotoxicity is an important issue in view of hepatic involvement and drug interaction.10\n\nThe medical imaging modalities provide the keystones to diagnose the hydatid cysts. Among all, first line diagnosis, differential diagnosis, staging, establishing the role in interventional management, and follow-up is given by high-resolution ultrasound imaging. Unenhanced CT is useful where or when the ultrasound is unsatisfactory, as may be seen with chest and brain hydatid cysts, detection of calcification, and in obese patients.11 These modalities delivery may further deteriorate and become unavailable, especially in war-torn areas. Areas affected by conflict usually face a lack of radiologists and equipment, a situation worsened by violent events. This is contrary to the increasing need for radiology services during such conflicts.,12 which in turn makes confirming the diagnosis more difficult.\n\nThis case brings into consideration the importance of recognition of co-infection in the endemic regions. Interdisciplinary management and vigilant follow-up may result in successful clinical outcomes therapeutically. Further research in immunological interplay between these two infections could provide better therapeutic approaches.\n\nWritten informed consent was obtained from the patient for publication of this case report and accompanying images.\n\nNo data are associated with this article.",
"appendix": "References\n\nThys S, Sahibi H, Gabriël S, et al.: Community perception and knowledge of cystic echinococcosis in the High Atlas Mountains, Morocco. BMC Public Health. 2019; 19: 118. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWen H, Vuitton L, Tuxun T, et al.: Echinococcosis: Advances in the 21st Century. Clin. Microbiol. Rev. 2019; 32(2): e00075–18. Published 2019 Feb 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVerma PK, Rohilla R, Natarajan V, et al.: A rare case of coexisting tuberculosis with hydatid disease from North India with review of literature. BMJ Case Rep. 2020; 13(9): e235301. Published 2020 Sep 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJalayeri MHT, Sharifi far RA, Lashkarbolouk N, et al.: The co-infection of pulmonary hydatid cyst, lophomoniasis and tuberculosis in a patient with resistant respiratory symptoms; a case report study. BMC Infect. Dis. 2024; 24: 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang YR, Gray DJ, Ellis MK, et al.: Human cases of simultaneous echinococcosis and tuberculosis - significance and extent in China. Parasit. Vectors. 2009; 2(1): 53. Published 2009 Nov 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaron EJ, Michael Miller J, Weinstein MP, et al.: A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM) a, Clinical Infectious Diseases.15 August 2013; 57(4): e22–e121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKotton CN, Lattes R: Parasitic Infections in Solid Organ Transplant Recipients. Am. J. Transplant. 2009; 9: S234–S251. 1600-6135. Publisher Full Text\n\nElfaky IO, Merghani TH, Elmubarak IA, et al.: Nutritional Status and Patterns of Anemia in Sudanese Adult Patients with Active Pulmonary Tuberculosis: A Cross-Sectional Study. Int. J. Mycobacteriol. Jan–Mar 2023; 12(1): 73–76. PubMed Abstract | Publisher Full Text\n\nEl-On J: Benzimidazole treatment of cystic echinococcosis. Acta Trop. 2003; 85(2): 243–252. Publisher Full Text\n\nReich R, Mulvaney P, Robinson-Bostom L: Chapter 31 - Antihelminthic Drugs.Sidhartha D, editors. Ray, Side Effects of Drugs Annual. Vol. 36. . Elsevier; 2014; pp. 457–464. 0378-6080. 9780444634078. Publisher Full Text\n\nAlshoabi SA, Alkalady AH, Almas KM, et al.: Hydatid Disease: A Radiological Pictorial Review of a Great Neoplasms Mimicker. Diagnostics (Basel). 2023; 13(6): 1127. Published 2023 Mar 16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRosenberger A, Adler O, Braun Y, et al.: Diagnostic radiology in wartime. Isr. J. Med. Sci. 1984; 20(4): 330–332. PubMed Abstract"
}
|
[
{
"id": "343283",
"date": "06 Feb 2025",
"name": "Alin Mihetiu",
"expertise": [
"Reviewer Expertise General Surgery",
"Liver Surgery",
"Hydatid Abdominal Surgery",
"Oncological Surgery",
"Laparoscopy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAlthough a clear causal link cannot be established between hydatid infection and the activation of tuberculosis, the association of these pathologies in the context of a precarious economic framework can still be noted. The decrease in immunity may be due to the demands of the immune mechanisms given by the echinococcus infection, and may predispose to the activation of the tuberculosis disease, but a clear causal link, both physio pathologically and statistically, cannot be affirmed.\nData are needed to detail the type of surgical intervention used in the approach to the hepatic hydatid cyst and the challenges that anesthesia and the postoperative evolution of such a case entail.\nWithout such details, the article lacks the practical side, it being more of a report with a unique character but without a direct causal link and remains only in the area of a unique association.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1412
|
https://f1000research.com/articles/12-1413/v1
|
26 Oct 23
|
{
"type": "Research Article",
"title": "Mobile applications (apps) for tobacco cessation: Behaviour change potential and heuristic analysis using the Mobile Application Rating Scale (MARS)",
"authors": [
"Bhargav Bhat",
"Prajna Pramod Nayak",
"Ramprasad Vasthare",
"Deepak Kumar Singhal",
"Bhargav Bhat",
"Ramprasad Vasthare",
"Deepak Kumar Singhal"
],
"abstract": "Background Given the high prevalence of tobacco use, India presents a significant challenge in tobacco control. Yet, the support received for tobacco cessation is suboptimal. Hence, the aim was to identify and heuristically evaluate ‘high-quality’ and ‘engaging’ tobacco cessation mobile apps using the Mobile Application Rating Scale (MARS). Also, to categorize and analyse their features with respect to engagement, functionality, aesthetics, and information quality.\n\nMethods A systematic search of tobacco cessation apps was done within app stores of prominent smartphone platforms developed by Apple and Android. The following search terms: ‘quit smoking,’ ‘smoking cessation, ‘stop smoking,’ ‘smoking therapy,’ ‘quit tobacco,’ ‘cigarette cessation,’ ‘cold turkey,’ and ‘quit cigarette.’ Pearson’s correlations were used to analyse correlations between app scores (Total score app-quality/mean score) and downloads/ratings and number of downloads with the overall MARS score. A Chi-square test was performed to analyse any association between app focus and app release dates.\n\nResults Total MARS scores ranged from 3.1 to 4.9. Quitsure app (4.9), Craving to Quit! app (4.8) and Stop Tobacco Mobile Trainer: Quit Smoking App (4.74) were ranked the highest according to the MARS overall mean score. Older apps focussed more on mere goal setting or substance use, as compared to behaviour change; whereas, recently developed apps are now focussing more on behaviour change.\n\nConclusions The content and functionality of behaviour change-focused apps were of higher quality than those of other app categories. These recently developed mHealth apps can effectively supersede the traditional smoking cessation methods.",
"keywords": [
"smoking cessation",
"mobile health",
"mHealth",
"tobacco use cessation",
"mobile app",
"oral health"
],
"content": "Introduction\n\nTobacco use is the world’s most significant threat that is responsible for numerous preventable morbidities, most of which have the potential to kill consumers prematurely. Six of the top eight causes of mortality have smoking as a risk factor. The 20th century has seen an estimated 100 million fatalities worldwide as a result of the tobacco epidemic.1 India is currently experiencing a second-stage tobacco pandemic. Each year, 800,000 to 900,000 people in India die from diseases linked to tobacco use. It is crucial to act swiftly to stop this preventable disease.2\n\nGiven the high prevalence of tobacco use, India represents a significant challenge in tobacco control. According to the latest Global Adult Tobacco Survey (GATS) India (2016–17), 28.6% of smokers in India use tobacco, with male smokers having a greater prevalence (42.4%) than female smokers (14.2%). According to this nationally representative survey, 52% of tobacco users are ready to give up the habit.3,4 Tobacco cessation programs run at hospitals and rehabilitation centres provide face-to-face and telephone-based behavioural interventions (e.g., brief motivational advice, group or individual counselling, telephone counselling and quit lines) and pharmacotherapy (e.g., nicotine replacement therapies, bupropion) to support smoking cessation. Yet, tobacco cessation support is suboptimal owing to the lack of access to smoking cessation resources, lack of clinician knowledge or skills, and lack of clinician time. The majority of people making independent attempts fail to maintain their quit status for even one month. Hence, use of mHealth intervention for smoking cessation represents one of the best methods to curb the global public health threat of the tobacco epidemic.5\n\nIn the recent times, mobile phones, the Internet and mobile communication have become an inevitable part of our lives. According to estimates, 3.5 billion smartphones were in use worldwide as of June 2020, providing a sizable number of users to help coordinate and conduct mobile interventions to distribute information.6 An “app” is the most frequent term for a mobile application that is created to run on portable wireless mobile phones like smartphones.7,8 With over three billion downloads of mHealth apps worldwide in 2015, an effective, high-quality smoking cessation app can be an easy-to-use resource that can provide personalized smoking cessation support to thousands of people, including remote smokers, at the right time and location. Past reviews show that mobile apps have tremendous behavioural change potential.6,7–9\n\nThe utilization of mobile applications in healthcare can offer a range of benefits, including ease of access to information and the potential for enhanced patient engagement and adherence to treatment. However, there are some drawbacks to the use of mobile applications, particularly as the information on apps may not be regulated. As a result, some of the apps that patients access may contain substantial inaccuracies.8\n\nThe use of smoking cessation interventions utilizing smartphone technology is on the rise globally. However, the effects on cessation rate and prevention of relapses are not often evaluated.10 Moreover, few studies are reporting the effectiveness of smartphone apps for tobacco cessation. What’s more, rankings within the leading app stores are highly volatile and primarily based on the usability of apps. Hence, the behaviour change potential of apps cannot be solely judged based on app ‘ratings’ or ‘popularity’ in app stores.\n\nRecently many evaluation criteria/scales have been developed to evaluate app efficacy. Evaluation based on addressing the 5 As (Ask, Advise, Assess, Assist and Arrange) of tobacco cessation, App Behaviour Change Scale (ABACUS), adherence to clinical practice guidelines for tobacco control, Mobile Application Rating Scale (MARS) have been commonly used in recent studies.11–15 The latter evaluation method, MARS was developed by Stoyanov SR, is widely used and validated by many studies (Figure 1).15–18 Hence, we aimed to identify and heuristically evaluate ‘high-quality’ and ‘engaging’ tobacco cessation mobile apps using MARS. The objectives were to identify tobacco cessation apps on Apple and Android app stores and to categorize and analyse their features as regards to engagement, functionality, aesthetics, and information quality. Thereby recommending directions for the improvement of these apps.\n\n\nMethods\n\nThe study was registered with Kasturba Hospital ethics committee, approval number [IEC2 – 19 (2022), dated 21/06/2022.\n\nA systematic search of tobacco cessation apps was done within the Apple and Android app stores. The following search terms were used: ‘smoking cessation, ‘quit smoking,’ ‘stop smoking,’ ‘smoking therapy,’ ‘quit tobacco,’ ‘cigarette cessation,’ ‘cold turkey,’ and ‘quit cigarette.’ All the apps rated 4* and above, with downloads of more than 10,000 were included in the study. Apps that did not target tobacco cessation and those not in English were excluded from the study. We also eliminated the duplicate apps, including earlier versions. To begin with, we identified all apps based on their focus area:\n\n• Substance use: information about the ill-effects of tobacco and thereby motivating users to quit.\n\n• Goal setting: monitoring and tracking the process of quitting.\n\n• Behaviour change: using therapeutic techniques such as cognitive behaviour therapy (CBT), acceptance commitment therapy (ACT) and mindfulness.\n\nSubsequently, extracted data from each app were assessed using the MARS rating scale. The MARS evaluation tool is divided into three broad sections: App overall quality, App subjective quality, and App specific quality. It consists of 23 questions designed to help analyse the mobile applications' engagement, functionality, aesthetics, information, and subjective quality. In addition, there are six additional app-specific questions that can be customized to represent the goal health behaviour/function of the application/study. The average scores for each of these four sub-schemes were calculated, and the average scores of these sub-quotas used to evaluate the overall quality score of the application ranged from 0 to 5. Therefore, the total score of these sub-categories would be 0 to 5 and the average score would be calculated by dividing the total score by 4, i.e., four domains. The subjective quality section of the App and the App-specific section of the App were calculated similarly. These, however, were considered as separate from the app quality score. (Figure 1)\n\nData regarding the App’s features were entered in a Microsoft Excel sheet v 2019 and subjected to statistical analysis to conclude. The two reviewers were trained in the use of MARS using a 37-minute video on YouTube. Subsequently, they conducted an independent assessment of a standard application and discussed their scores.\n\nData were analysed using descriptive and analytical statistics. Quantitative variables were expressed as means and standard deviations. Kendall’s coefficient of concordance was used to calculate the interrater agreement between two raters. Pearson’s correlations were used to analyse correlations between app scores (Total score app-quality/mean score) and downloads/ratings and number of downloads with the overall MARS score. A Chi-square test was performed to analyse any association between app focus and app release dates with a p-value of <0.05 considered as significant.\n\n\nResults\n\nA total of 670 apps were retrieved from within the Apple and Android App stores (Android 482; iOS 188). After screening the description available on the web page, 48 apps were excluded as they were duplicate apps present in both the Play stores. [19] Of the 622 apps filtered, 558 apps didn’t meet the inclusion criteria and were excluded from the study. After all the exclusions, 20 apps (Android,17; iOS, 3) were subjected to analysis. A flowchart illustrating the selection and exclusion of apps at various stages of the study is shown in the Figure 2. Interrater agreement between two raters showed high reliability (0.804).\n\nAll apps were free in their basic version, but 14 required payments to view their upgraded versions. As per their primary focus area, two apps targeted only substance use, while 14 apps focused on goal setting and four apps were aimed at behaviour change (Figure 3). Five apps had an app-based community that allowed virtual help. All apps were available for general age groups (Table 1). Fifteen apps had second or higher versions and the last update of most apps was after June 2023. The mean app rating by consumers in the Google Play store was more than 4 (according to the inclusion criteria) (Table 2).\n\nTable 3 gives the mean app quality ratings scored under engagement, functionality, aesthetics and information domains. The Craving To Quit! and QuitSure apps recorded a score of 4.75 and above in all four domains. Whereas, the SmokeFree: Quit smoking slowly and Qwit apps had scores of 3.7 or below in all the domains. The average score of the above four domains, that is the App quality mean score, was highest for the QuitSure app (4.88) and Craving To Quit! app (4.83).\n\nThe MARS overall mean score was then calculated by calculating an average of App quality mean score, App subjective mean score and App specific mean score. We observed that the QuitSure app (4.9), Craving To Quit! app (4.8) and Stop Tobacco Mobile Trainer: Quit Smoking App (4.74) were ranked the highest according to the MARS overall mean score. Whereas, Smokefree: Quit smoking slowly (3.1) and Qwit (3.2) scored the least (Table 4).\n\nWe examined if there was any correlation between average review scores and overall MARS scores. There was a moderate, positive correlation seen, which was statistically significant (r = 0.395, n = 20, p = 0.038). Also, a moderate, positive correlation between the number of downloads and the overall MARS score was seen (r = 0.480, n = 20, p = 0.013).\n\nA Chi-square test was performed to analyse any association between app focus and app release dates. Older apps focussed more on mere goal setting or substance use, as compared to behaviour change. Apps that have been recently developed are now focussing more on behaviour change and these results were statistically significant (P value = 0.000).\n\n\nDiscussion\n\nThis study reviewed mobile applications for quitting smoking and used the MARS scale to rate the apps' quality. It is one of the most popular scales for evaluating the value and content of mHealth apps. It is a multidimensional tool for assessing the quality using semantic analysis and synthesis of existing literature.15 Engagement, functionality, aesthetics, and information quality are the four main dimensions that are assessed (Figure 1). The initial validation study demonstrated strong objectivity and reliability for the overall scale and subscales.16,17 The MARS' applicability for quality assessment was proved by a validation study with metric evaluation.17 As a result, MARS might be utilised to make the quality of apps transparent to patients and healthcare stakeholders.\n\nOur study found more than 622 smoking cessation apps in both platforms. It is concerning that the app stores for smoking cessation applications is saturated with apps of low quality, perhaps making it difficult for users who aren't the most selective to find higher-quality apps. This study reviewed 20 of these apps aimed at helping people quit smoking in order to evaluate their quality and distinguishing characteristics.\n\nIn this study, we classified apps based on their primary goals: goal setting, substance use, and behaviour change. Most of apps with the primary focus as goal setting functioned as trackers for cravings, calendars, number of cigarettes not smoked and the amount of money saved. These results are similar to the study conducted by Vilardaga et al.,9 and Hoeppner et al.,11\n\nThe results of our study are consistent with the results of earlier reviews. Education and behavioural methods are the two areas that most frequently appear in mHealth apps.5,9,18 By changing their behaviour, people can better their prognosis, lessen pain or suffering, and take control of their health. According to the findings of our study, the apps that focus on behaviour modification had higher user ratings and overall MARS scores with many features.\n\nGoal-setting and substance use are two additional crucial components of tobacco cessation applications. These apps function by asking users to enter their cigarette consumption before creating their own objective goals for quitting. The app also offers resources and data to help users track their progress towards their goals and maintain their motivation to stop using tobacco. However, it has been noted that the number of goal-setting apps has dropped over time.\n\nOur study thus points to a potential market for developing behaviour change targeting apps that offer knowledge and expertise for controlling the quitting process. Like in previous studies, apps that utilize behaviour change and cognitive techniques, which are evidence based, such as the 5 A’s, acceptance and commitment therapy and hypnosis were having the highest MARS score among all the apps.5,13,14\n\nThe aesthetic and information subscales had slightly lower mean scores than the engagement and functionality subscales, which shows that even though the apps had good graphics, a pleasing visual appearance, and accurate descriptions and information, it is still crucial that the target audience is well-engaged and is persuaded to use the apps. The results of previous studies using MARS for quality assessment of mobile apps for the management of tinnitus20 and asthma management21 showed the engagement and aesthetic scores were lower, which indicates that these factors are less important in the design of health management apps. These noticeable features could be improved and developed in the next version of the apps.\n\nGenerally, while creating an app, developers must take into account both intriguing and crucial features as well as high-quality, fact-based material. The typical mean scores for engagement and functionality point to prospective areas that could be improved. Further research like randomised controlled trials need to be done to determine whether these apps result in behaviour change, and not just improvement in knowledge.\n\nThis study contains some limitations. First, popularity is the basis for app store rankings. As a result, the top apps that each search displayed did not always represent the best apps. We did not have access to numerous international apps created exclusively for use within each nation as phone numbers were required for registration and app usage. Applications go through upgrades and modifications frequently. Several apps assessed may have been upgraded to newer versions since the MARS evaluation was conducted. The most recent version and these updates could change the outcome of this research. Also, given that the apps were only used once and the quality ratings were based on brief usage, it's probable that some features were overlooked by the reviewers while evaluating the apps. The strength of our study is that the raters paid for the upgraded version of a number of apps to access the full version so as to not miss any distinguishable features of those apps.\n\n\nConclusions\n\nThe content and functionality of behaviour change-focused applications were of higher quality than those of other app categories. These recently developed mHealth apps can effectively supersede the traditional smoking cessation methods. This study can be a reference for those who use and create smoking cessation apps. Users can select the best smoking cessation app for their needs by using the classification of the application.",
"appendix": "Data availability\n\nOpen Science Framework: Underlying data for ‘Mobile applications (apps) for tobacco cessation: Behaviour change potential and heuristic analysis using the Mobile Application Rating Scale (MARS)’, https://www.doi.org/10.17605/OSF.IO/JNBPF. 19\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nChhabra A, Hussain S, Rashid S: Recent trends of tobacco use in India. J. Public Health. 2021 Feb; 29: 27–36. Publisher Full Text\n\nTobacco Cessation in Dental Settings- Reference Manual for Dental Professionals: Reference Source\n\nNagpal R, Nagpal N, Mehendiratta M, et al.: Usage of betel quid, areca nut, tobacco, alcohol and level of awareness towards their adverse effects on health in a north Indian rural population. Oral Health Dent Manag. 2014 Mar 1; 13(1): 81–86. PubMed Abstract\n\nTobacco dependence treatment guidelines: Reference Source\n\nBustamante LA, Ménard CG, Julien S, et al.: Behavior change techniques in popular mobile apps for smoking cessation in France: content analysis. JMIR Mhealth Uhealth. 2021 May 13; 9(5): e26082. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUdugama B, Kadhiresan P, Kozlowski HN, et al.: Diagnosing COVID-19: The Disease and Tools for Detection. ACS Nano. 2020; 14(4): 3822–3835. Publisher Full Text\n\nNayak P, Nayak S, Vikneshan M, et al.: Smartphone apps: A state-of-the-art approach for oral health education. Journal of Oral Research. 2019 Oct 31; 8(5): 386–393. Publisher Full Text\n\nParker K, Bharmal RV, Sharif MO: The availability and characteristics of patient-focused oral hygiene apps. Br. Dent. J. 2019 Apr 26; 226(8): 600–604. PubMed Abstract | Publisher Full Text\n\nVilardaga R, Casellas-Pujol E, McClernon JF, et al.: Mobile applications for the treatment of tobacco use and dependence. Curr. Addict. Rep. 2019 Jun 15; 6: 86–97. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWallace S, Clark M, White J: “It’s on my iPhone”: attitudes to the use of mobile computing devices in medical education, a mixed-methods study. BMJ Open. 2012; 2(4): e001099. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHoeppner BB, Hoeppner SS, Seaboyer L, et al.: How smart are smartphone apps for smoking cessation? A content analysis. Nicotine Tob. Res. 2016 May 1; 18(5): 1025–1031. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRobinson CD, Seaman EL, Grenen E, et al.: A content analysis of smartphone apps for adolescent smoking cessation. Transl. Behav. Med. 2020 Feb; 10(1): 302–309. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThornton L, Quinn C, Birrell L, et al.: Free smoking cessation mobile apps available in Australia: a quality review and content analysis. Aust. N. Z. J. Public Health. 2017 Dec 1; 41(6): 625–630. PubMed Abstract | Publisher Full Text\n\nSeo S, Cho SI, Yoon W, et al.: Classification of smoking cessation apps: quality review and content analysis. JMIR Mhealth Uhealth. 2022 Feb 17; 10(2): e17268. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStoyanov SR, Hides L, Kavanagh DJ, et al.: Mobile app rating scale: a new tool for assessing the quality of health mobile apps. JMIR Mhealth Uhealth. 2015 Mar 11; 3(1): e3422. Publisher Full Text\n\nStoyanov SR, Hides L, Kavanagh DJ, et al.: Development and validation of the user version of the Mobile Application Rating Scale (uMARS). JMIR Mhealth Uhealth. 2016 Jun 10; 4(2): e5849. Publisher Full Text\n\nTerhorst Y, Philippi P, Sander LB, et al.: Validation of the Mobile Application Rating Scale (MARS). PLoS One. 2020 Nov 1; 15(11 November): e0241480. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoy A, Nayak PP, Shenoy PR, et al.: Availability and Content Analysis of Smartphone Applications on Conservative Dentistry and Endodontics Using Mobile Application Rating Scale (MARS). Current Oral Health Reports. 2022 Dec; 9(4): 215–225. Publisher Full Text\n\nNayak PP: Underlying data for ‘Mobile applications (apps) for tobacco cessation: Behaviour change potential and heuristic analysis using the Mobile Application Rating Scale (MARS)’. [Dataset]. Open Science Framework. 2023. Publisher Full Text\n\nRamsey RR, Caromody JK, Voorhees SE, et al.: A Systematic Evaluation of Asthma Management Apps Examining Behavior Change Techniques. Journal of Allergy and Clinical Immunology: In Practice. 2019 Nov 1; 7(8): 2583–2591. Publisher Full Text\n\nSereda M, Smith S, Newton K, et al.: Mobile apps for management of tinnitus: Users’ survey, quality assessment, and content analysis. JMIR Mhealth Uhealth. 2019; 7(1): e10353. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "236779",
"date": "25 Jan 2024",
"name": "Cristina Rey-Reñones",
"expertise": [
"Reviewer Expertise mhealth",
"tobacco",
"nursing"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Author's,\nI trust this message finds you well. I recently read your article titled \"Mobile Applications (Apps) for Tobacco Cessation: Behavior Change Potential and Heuristic Analysis Using the Mobile Application Rating Scale (MARS) [Version 1; Peer Review: Awaiting Peer Review].\" I commend you on addressing a pertinent contemporary need in your research.\nThe work is presented with clarity and precision. Notably, a total of 21 bibliographic citations are included, with 13 (61%) sourced from the last five years.\nIn light of the commendable effort, I would like to offer a couple of constructive suggestions for consideration. Firstly, it would be beneficial to specify which of the applications studied have scientific evidence supporting their efficacy, effectiveness, and efficiency. This additional detail would enhance the comprehensiveness of your analysis.\nAdditionally, I would like to suggest broadening the scope of your study by incorporating other forms of tobacco consumption, such as \"vaping\" or \"e-cigarette,\" in addition to traditional tobacco use. This expansion would contribute to a more comprehensive understanding of the subject matter.\nOnce again, congratulations on your valuable contribution to the field. I appreciate your dedication to advancing research in this area.\nKind regards,\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12832",
"date": "22 Nov 2024",
"name": "Prajna Nayak",
"role": "Author Response",
"response": "We thank the reviewer for their suggestions, we have now made the following corrections: 1. As mentioned by the reviewer to add scientific evidence available for the applications studied, we have now added a column in table 2 on the sources of information if available. This will enable readers on the legitimacy of the source. 2. We could not add the incorporate other forms of tobacco consumption, such as \"vaping\" or \"e-cigarette,\" in addition to traditional tobacco use. Because, we had not used these terms in our ‘Search strategy’. Addition of these would have resulted in apps designed to assist in quitting e-cigarettes too. Hence, we are afraid we will not be able to incorporate them, now."
}
]
},
{
"id": "327336",
"date": "18 Oct 2024",
"name": "Ranjani Harish",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral Comments: The aim of the study was to identify tobacco cessation apps on Apple and Android app stores and to categorize and analyse their features as regards to engagement, functionality, aesthetics, and information quality. Thereby recommending directions for the improvement of these apps.\nSpecific Comments: Title:\n\nPlease specify the type of review in the title to facilitate better understanding of the article.\n\nAbstract:\nMARS (Mobile Application Rating Scale) could have been incorporated into the keywords to enhance the specificity.\nIntroduction\nKindly give reference for the following lines in the introduction section: “The majority of people making independent attempts fail to maintain their quit status for even one month.” The second para of this section provides statistics on tobacco cessation from India. However, the following paragraph discusses global statistics on smartphone users, which appears to be out of sync with the flow of information. To maintain coherence, it would be better to align the information properly. The rationale of the review was well articulated in the introduction although a little more background on MARS and its scoring system and how it helps in heuristically evaluating the mhealth applications could be provided to strengthen the foundation of the study.\nMethodology:\nThe introduction highlights that rankings in app stores are highly volatile and primarily influenced by app usability, meaning that an app's behaviour change potential cannot be fully assessed based on its ratings or popularity alone. However, the inclusion criteria in the methods section focus on selecting apps with a rating of 4 stars or higher and more than 10,000 downloads. Justify. The inclusion of only apps with a rating of 4 stars or higher and over 10,000 downloads might exclude newer or less popular apps that could still be effective. This introduces a bias towards more established apps. Kindly justify. The reviewers were trained using a 37-minute YouTube video. Please answer the following questions: a) It may not be sufficient for thorough, expert-level assessment using the MARS tool. Kindly comment. b) While a high interrater reliability (0.804) is reported, no additional details are provided on how discrepancies between reviewers were resolved. This could affect the validity of the scoring and analysis if disagreements were not consistently addressed. Justify. c) How reliable and authentic was the video? It is suggested to include the link for the video in the references.\n\nThere’s no mention of how frequently the apps were updated or if the study accounted for updates during the research period in the methods section. App features and functionalities can change significantly with updates, which could affect the evaluation. It is suggested to include details regarding the same. Less information is provided on the availability of the mhealth application, especially if is it limited to India (developed) or Indian context. This may be an important factor as some of the apps belonging to the western population could not be practical for lifestyle or behaviour change therapies among Asian Indians. Statistical analyses used in the review seem basic thus undermining the actual benefits of the application and how it could be practically applied. Although the review outlines the combined effects of all the 20 applications, additional specifications or features of at least the top 5 applications could be briefed out to demonstrate how pragmatic these apps are for everyday practise.\nResults:\nIt is recommended to provide a separate breakdown in Figure 2 for each reviewer, rather than presenting an overall summary. For example, indicate how many apps were identified by Reviewer 1 and how many were identified by Reviewer 2 using the search terms. While the study title emphasizes behaviour change, \"Mobile applications (apps) for tobacco cessation: Behaviour change potential and heuristic analysis using the Mobile Application Rating Scale (MARS),\" the majority of the apps reviewed (14) primarily focused on goal-setting, with only 4 targeting behaviour change directly. Justify. The final number of apps subjected to analysis (20 out of 670) is very small (only 3 apps from iOS). The sample size may be too small to yield reliable or meaningful statistical significance. This limits the generalizability of the findings \"Chi-square test was performed to analyse any association between app focus and app release dates. Older apps focused more on mere goal setting or substance use, as compared to behaviour change. Apps that have been recently developed are now focusing more on behaviour change and these results were statistically significant (P value = 0.000).\"\nWhat is the definition of older apps? According to table 1, 50% apps were release between years 2019-2023 and an equal number were updated in 2023. This contradicts the results where the authors have mentioned that there were only 4 apps targeting behaviour change.\n\nTable showing correlation and chi square test is missing. It is suggested to remove pie chart as this is not adding any value to the manuscript. Further explanation of statistical tests, confidence intervals, and potential confounding factors would enhance the clarity and rigor of the analysis. Additionally, providing more detail on the interpretation of correlations and the significance of app focus trends would strengthen the discussion of results.\nDiscussion:\nThis is the line from discussion section: “According to the findings of our study, the apps that focus on behaviour modification had higher user ratings and overall MARS scores with many features.” a) Since, authors are talking a lot about these apps. In the results section as well It is suggested to include the app names based on this categorisation in the results section for clearer reference. b) Also, while the study notes that most apps focussed on goal setting. There is little exploration of the implications of having a majority of apps focused on goal setting rather than behaviour change.\n\nSome points mentioned in other sections of the study are repeated, such as the focus on the MARS scale and its dimensions. Kindly avoid such repetitions. \"Our study found more than 622 smoking cessation apps in both platforms. It is concerning that the app stores for smoking cessation applications is saturated with apps of low quality, perhaps making it difficult for users who aren't the most selective to find higher-quality apps.\"\nFor the above statement, What criteria were used to determine low quality of an app?\n\nThe discussion mentions similarities with previous studies but does not provide a detailed comparison or analysis of how the current findings add to or differ from existing literature. The recommendation for developing more behavior change-focused apps lacks specificity and concrete suggestions on features. Kindly review the calculation for the apps excluded. The number mentioned in results (558) and the number mentioned in fig 2 (54) gives a difference of 10 which is missed out in the review. Recheck and update the table or the count. While the discussion does a great job of highlighting the importance of behavior change apps, it could benefit from a deeper exploration of why behavior change techniques (e.g., cognitive-behavioral therapy, acceptance and commitment therapy) are more effective in driving smoking cessation. A more detailed explanation of the mechanisms behind these techniques, backed by literature, would strengthen the argument and provide additional value to readers who may be unfamiliar with these approaches.\nFinal Comments:\n\nThe study aimed to evaluate tobacco cessation apps on Apple and Android app stores, analyzing their features related to engagement, functionality, aesthetics, and information quality. However, it faces issues with justifying its inclusion criteria, addressing the small sample size, and providing specific recommendations for improving behaviour change-focused apps.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12833",
"date": "22 Nov 2024",
"name": "Prajna Nayak",
"role": "Author Response",
"response": "General Comments: The aim of the study was to identify tobacco cessation apps on Apple and Android app stores and to categorize and analyze their features as regards to engagement, functionality, aesthetics, and information quality. Thereby recommending directions for the improvement of these apps. Specific Comments: Title: Please specify the type of review in the title to facilitate better understanding of the article. Author Response : We thank the reviewer for their suggestion, the ‘abstract’ has been edited to make it clear. We could not add the type of review in the title, as it can lengthen the title further (19 words). Abstract: MARS (Mobile Application Rating Scale) could have been incorporated into the keywords to enhance the specificity. Author Response : We have now added it ma’am. Introduction Kindly give reference for the following lines in the introduction section: “The majority of people making independent attempts fail to maintain their quit status for even one month.” The second para of this section provides statistics on tobacco cessation from India. However, the following paragraph discusses global statistics on smartphone users, which appears to be out of sync with the flow of information. To maintain coherence, it would be better to align the information properly. The rationale of the review was well articulated in the introduction although a little more background on MARS and its scoring system and how it helps in heuristically evaluating the mhealth applications could be provided to strengthen the foundation of the study. Author Response : We have now added the reference, ma’am. .We have now provided India statistics to synchronize with the tobacco cessation statistics. We have now provided details on the MARS scale. More details are available in the methodology section ma’am. Methodology: The introduction highlights that rankings in app stores are highly volatile and primarily influenced by app usability, meaning that an app's behavior change potential cannot be fully assessed based on its ratings or popularity alone. However, the inclusion criteria in the methods section focus on selecting apps with a rating of 4 stars or higher and more than 10,000 downloads. Justify. The inclusion of only apps with a rating of 4 stars or higher and over 10,000 downloads might exclude newer or less popular apps that could still be effective. This introduces a bias towards more established apps. Kindly justify. The reviewers were trained using a 37-minute YouTube video. Please answer the following questions: a) It may not be sufficient for thorough, expert-level assessment using the MARS tool. Kindly comment. b) While a high interrater reliability (0.804) is reported, no additional details are provided on how discrepancies between reviewers were resolved. This could affect the validity of the scoring and analysis if disagreements were not consistently addressed. Justify. c) How reliable and authentic was the video? It is suggested to include the link for the video in the references. There’s no mention of how frequently the apps were updated or if the study accounted for updates during the research period in the methods section. App features and functionalities can change significantly with updates, which could affect the evaluation. It is suggested to include details regarding the same. Less information is provided on the availability of the mhealth application, especially if is it limited to India (developed) or Indian context. This may be an important factor as some of the apps belonging to the western population could not be practical for lifestyle or behavior change therapies among Asian Indians. Statistical analyses used in the review seem basic thus undermining the actual benefits of the application and how it could be practically applied. Although the review outlines the combined effects of all the 20 applications, additional specifications or features of at least the top 5 applications could be briefed out to demonstrate how pragmatic these apps are for everyday practice. Author Response : We have now added the justification in the 1st para of Discussion, ma’am. We have now added the justification in the 1st para of Discussion and also mentioned in the limitations, ma’am. Since the video was uploaded by the developer of the scale himself, we used it as a reference for understanding the scale better. We have also added on how the discrepancies were resolved in the Methods section. (13) MARS training video - YouTube , we have now added the link to the video, ma’am. As the study was conducted in a relatively short period of time, we have not mentioned updates during study period. Since the Apple and Android App stores both show all the apps, irrespective of the country that developed the app, we could not isolate the Indian apps. Also, we did not have access to numerous international apps created exclusively for use within each nation as phone numbers were required for registration and app usage. As this could lengthen the manuscript, we could not brief on top 5 apps. Instead, we have tried to summarize the results of top 20 apps distinctly. Results: It is recommended to provide a separate breakdown in Figure 2 for each reviewer, rather than presenting an overall summary. For example, indicate how many apps were identified by Reviewer 1 and how many were identified by Reviewer 2 using the search terms. While the study title emphasizes behavior change, \"Mobile applications (apps) for tobacco cessation: Behavior change potential and heuristic analysis using the Mobile Application Rating Scale (MARS),\" the majority of the apps reviewed (14) primarily focused on goal-setting, with only 4 targeting behavior change directly. Justify. The final number of apps subjected to analysis (20 out of 670) is very small (only 3 apps from iOS). The sample size may be too small to yield reliable or meaningful statistical significance. This limits the generalizability of the findings \"Chi-square test was performed to analyze any association between app focus and app release dates. Older apps focused more on mere goal setting or substance use, as compared to behavior change. Apps that have been recently developed are now focusing more on behavior change and these results were statistically significant (P value = 0.000).\" What is the definition of older apps? According to table 1, 50% apps were release between years 2019-2023 and an equal number were updated in 2023. This contradicts the results where the authors have mentioned that there were only 4 apps targeting behavior change. Table showing correlation and chi square test is missing. It is suggested to remove pie chart as this is not adding any value to the manuscript. Further explanation of statistical tests, confidence intervals, and potential confounding factors would enhance the clarity and rigor of the analysis. Additionally, providing more detail on the interpretation of correlations and the significance of app focus trends would strengthen the discussion of results. Author Response : Though both authors downloaded, selected and excluded apps together and then reviewed each app independently. Since we had to unbiasedly select the apps out of 54 apps, we included only the highly rated and most downloaded apps. Focus of the apps were checked later during the study. Nevertheless, other 14 apps, though had primary focus as goal setting, also had behavior counselling in their content. Hence, we have included them. Though we initially got 670 apps, the actual tobacco cessation apps were only 54. (Figure 2 flowchart for app identification). Hence, 20 out of 54 were selected, ma’am. We have now added a table mentioning the app release dates and app primary focus. (Table 6). We have now added it ma’am (Table 5) We have removed the pie chart now. We have now mentioned. Discussion: This is the line from discussion section: “According to the findings of our study, the apps that focus on behavior modification had higher user ratings and overall MARS scores with many features.” a) Since, authors are talking a lot about these apps. In the results section as well It is suggested to include the app names based on this categorization in the results section for clearer reference. b) Also, while the study notes that most apps focused on goal setting. There is little exploration of the implications of having a majority of apps focused on goal setting rather than behavior change. Some points mentioned in other sections of the study are repeated, such as the focus on the MARS scale and its dimensions. Kindly avoid such repetitions. \"Our study found more than 622 smoking cessation apps in both platforms. It is concerning that the app stores for smoking cessation applications is saturated with apps of low quality, perhaps making it difficult for users who aren't the most selective to find higher-quality apps.\" For the above statement, What criteria were used to determine low quality of an app? The discussion mentions similarities with previous studies but does not provide a detailed comparison or analysis of how the current findings add to or differ from existing literature. The recommendation for developing more behavior change-focused apps lacks specificity and concrete suggestions on features. Kindly review the calculation for the apps excluded. The number mentioned in results (558) and the number mentioned in fig 2 (54) gives a difference of 10 which is missed out in the review. Recheck and update the table or the count. While the discussion does a great job of highlighting the importance of behavior change apps, it could benefit from a deeper exploration of why behavior change techniques (e.g., cognitive-behavioral therapy, acceptance and commitment therapy) are more effective in driving smoking cessation. A more detailed explanation of the mechanisms behind these techniques, backed by literature, would strengthen the argument and provide additional value to readers who may be unfamiliar with these approaches. Author Response : We have now named those apps focusing on behavior change in the results section. Although the primary focus of majority of apps was goal setting, they also had behavior modification components in them. We have now removed the repetitions, ma’am. Most of the other apps had mere goal setting or basic details of health affects before and after quitting tobacco. Hence we had mentioned like so. We thank the reviewers for drawing attention on this, and we have now corrected the sentence. We have now added. We have now added ma’am. We have corrected it. We have now briefly explained important behavior change techniques for smoking cessation."
}
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}
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https://f1000research.com/articles/12-1413
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https://f1000research.com/articles/12-117/v1
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01 Feb 23
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{
"type": "Research Article",
"title": "Kidney and liver histology in tumour-induced rats exposed to non-contact electric fields",
"authors": [
"Firman Alamsyah",
"Nisrina Firdausi",
"Subekti Evi Dwi Nugraheni",
"Ahmad Ghitha Fadhlurrahman",
"Luthfi Nurhidayat",
"Rarastoeti Pratiwi",
"Warsito Purwo Taruno",
"Nisrina Firdausi",
"Subekti Evi Dwi Nugraheni",
"Ahmad Ghitha Fadhlurrahman",
"Luthfi Nurhidayat",
"Rarastoeti Pratiwi",
"Warsito Purwo Taruno"
],
"abstract": "Background: There were an estimated 2.1 million breast cancer diagnoses in 2018 worldwide, which is about 11.6% of the total cancer incidence. A novel modality of cancer treatment based on exposure to non-contact electric fields has been developed to reduce cancer incidence. However, the safety of the electric field exposure was not fully investigated. Therefore, the purpose of this study is to observe the safety of the electric field exposure on renal and liver structure. Methods: Female Sprague-Dawley rats were divided into one control group and three treatment groups. Animals were treated with 7,12-dimethylbenz[a]anthracene for mammary tumour induction and exposed to non-contact electric fields individually for 10 hours a day for three weeks. Fresh samples of the kidney and liver were collected for observing structural damage in both organs. The two organs were prepared for histopathological cross-sectioning using the paraffin method and Hematoxylin & Eosin staining followed by histological scoring using the post-examination masking method. Results: The damages found in the kidney were the following: thickening of Bowman capsule, karyolysis, karyorrexhis, pyknosis, cloudy swelling, epithelial sloughing, inflammation, haemorrhage, and congestion. The number of inflammation and haemorrhage in the kidney structure of the placebo group was the lowest and significantly different from the three other groups. All damages in the kidney were also found in the liver, but each showed different levels of damage. The damages in the kidney and liver caused by the exposure were not significant. Conclusions: The non-contact electric fields were not harmful to renal and liver structure in tumour-induced rats. Instead, it may increase the renal function in normal rats.",
"keywords": [
"damages",
"histology",
"kidney",
"liver",
"non-contact electric field",
"ECCT"
],
"content": "Introduction\n\nThe knowledge that electric fields can induce biological effects was revealed in the 19th century. Many studies were conducted which provided evidence that exposure to electric fields can generate alterations within living things.1 Some studies have examined the effects generated by electric fields on cell functions.2 Kirson et al.3 also reported that electric field intensity within a cell is less than 10 V/cm, but in a cell membrane, it may gain 105 V/cm. At the organ level, the kidney and liver have the dielectric property that exhibits a time-temperature dependence.4–6 Therefore, they possess electrical conductivity and permittivity.5,6\n\nPorter et al.7 explained that the knowledge of dielectric properties of biological tissues is valuable and useful in several applications of medical device, including cancer detection and treatment. As proof of that, the proliferation of cancer cells was successfully inhibited under exposure to intermediate frequency and low-intensity electric fields.3,8–11 They use intermediate frequency to treat cancer because it specifically targets cancer cells and does not affect normal cells due to their higher membrane potential than that of cancer cells.12,13 In our preliminary study, mammary tumour-induced mice that were exposed to intermediate frequency (100 kHz) and low-intensity (18 Volt peak to peak/Vpp) non-contact electric fields showed no histological alterations in mammary and skin tissues.8 Furthermore, we developed non-contact electric fields to avoid dermatitis due to the direct contact between the electrodes and the skin, as reported by Kirson et al.3 This novel modality has the potential to decrease the global cancer burden; 2.1 million people around the world were diagnosed with breast cancer in 2018, which is 11.6% of the total cancer incidence.14\n\nAlthough non-contact electric fields-based therapy has the potential to treat cancer, the safety of this kind of therapy when treating healthy tissues should be investigated. This is because injuries may occur after exposure to electric fields due to the dielectric property of the kidney and liver, which may interact with electrostatic waves. Therefore, it is important to investigate the abnormalities in the kidney and liver under exposure to electric fields during cancer treatment. The aim of this work was to investigate the safety of non-contact electric fields of strength 100 kHz-18 Vpp on the kidney and liver in the animal tumour model, with a focus on possible histological alterations in the organs. We hypothesised that exposure to non-contact electric fields would not affect the structure of the kidney and liver significantly. According to our knowledge, this is the first study investigating the abnormalities in the kidney and liver under exposure to 100 kHz intermediate frequency and low-intensity non-contact electric fields.\n\n\nMethods\n\nThe experimental design and procedures, experimental animals, animal care and monitoring, housing and husbandry, sample size, inclusion and exclusion criteria, randomisation and blinding in this study were the same as the ones that have been previously reported.9 For this study, 40 5-week-old healthy female Sprague Dawley (SD) rats (Rattus norvegicus, Berkenhout 1769) weighing 50−80 g were used. This rat strain is one of the animals used as animal tumor models to study human breast cancer, since it has 98% genetic homology with humans.15 These rats were provided by the Integrated Research and Testing Laboratory (LPPT) of Universitas Gadjah Mada (UGM), and never used for other studies. Rats that were sick or showing symptoms of disorder were excluded from the study. The rats were placed into polypropylene cages for one week of acclimatization. The cages were communal home cages with a size 50 × 40 cm2 and the base was covered with rice hulls bedding. We prepared eight communal cages with each cage consisted of 5 animals. The lighting conditions in the animal’s room during the day came from light from the lamp, while at night it was total darkness (12L:12D photoperiod). We maintained room temperature to avoid dehydration during exposure to the electric field at 23–26°C with an average relative humidity of 81.09%.\n\nWe divided the animals into one control group (non-induction and non-therapy or NINT) and three treatment groups, namely placebo (non-induction and therapy or NIT), DMBA-induced mammary tumours without therapy (induction and non-therapy or INT), and DMBA induced mammary tumours with therapy (induction and therapy or IT) group. Using the Federer formula, the sample size in each group was calculated, in which 6 biological replicates were used for each group11 and they were randomly selected to be assigned to the control and treatment groups.9\n\nWe administered a single dose of 7,12-dimethylbenz[a]anthracene (DMBA), 20 mg/kg body weight, to induce mammary tumours in rats in INT and IT groups. The administration of DMBA was conducted twice weekly for five weeks. This carcinogenic agent has been widely used in many mammary tumour studies using SD rats.16,17 Furthermore, the rats in the NIT and IT groups were treated with exposure to intermediate frequency (100 kHz) and low-intensity (18 Vpp) electric fields for 10 hours daily for 21 days in modified individual cages.9 Mammary tumours were palpated every two days with a digital caliper and their size (cm2) was tabulated. Nodule size were not measured in volume due to tool limitations. All tumour measurements were performed by the same investigator (NF). The therapy was terminated once the mammary tumours increased to 2.25 cm2 in size or therapy was completed on day 21. All rats were returned to their communal cages every day after therapy had completed.\n\nIndividual cages were cleaned daily by removing rat droppings and changing feed and water.9 Rat fur was given picric acid as an individual marker to avoid potential confounders, while rat cages were labeled with paint markers as group markers. Each work in this study, such as DMBA administration, euthanised rat dissection, kidney and liver sample fixation and data analysis, was carried out by different investigators. One investigator (FA) controlled and monitored all works in this study.\n\nAfter completion of the treatment, all animals were euthanised under anaesthesia using an overdose of ketamine (150 mg/kg of body weight) via intramuscular injection. The animals were dissected ventrally side up on a dissected box by the same surgeon (AGF).9 Two kidneys and two liver organs from different rats were collected randomly from each group. These 16 organs were used for histological examination. The number of samples used for histopathological examination was representative.\n\nSamples of the left kidney were taken from all groups by necropsy, washed using physiological saline (0.9% NaCl) and then fixed using 10% neutral buffered formalin (NBF). This organ was prepared for histopathological cross-sections using the paraffin method and hematoxylin and eosin (H&E) staining with a slightly modified protocol adapted from Bancroft and Cook.18 A piece of the organ that has been fixed then dehydrated using ethanol with a grade of 70%, 80%, 90%, and 100% for 2-3 repetitions, then followed by 4 hours clearing process with xylol at room temperature. Furthermore, the organ was infiltrated by putting it in the liquid paraffin at 60oC for 50 minutes with 3 repetitions. The next step was embedding which is putting the organ in a paraffin mold that contain liquid paraffin, then cooling it at room temperature. Then paraffin block which contains the organ was sectioned with 4-5 μm thickness. Then the organ slices were placed on a glass slide and deparaffinized by dipping them in xylol for 3x5 minutes. Then dehydration was performed using graded alcohol 96%, 90%, 80%, 70%, 50%, and distilled water for 1 minute each. The slides were then dipped in a solution of hematoxylin dye for 2-5 minutes, and dehydrated with 50% and 70% alcohol. Furthermore, it was dipped in eosin dye for 5-10 minutes, and dehydrated with 70%, 80%, 90%, and 96% alcohol. The last step was clearing for 15 minutes in xylol, and finally covered the slide using a cover glass.\n\nHistopathological scoring of the kidneys was performed using the post-examination masking method combined with the ordinal scoring method.19 The scoring referred to the endothelial-glomerular-tubular-interstitial (EGTI) system20 that adjusted to the research requirements by replacing the endothelial parameter with the number of congestions (Table 1). The scoring was performed on the renal cortex and medulla in 100 fields per group with 40x objective lens magnification. Microphotographs were taken using Leica DM750 photomicrographic microscope. Kidney sample fixation and histopathological analysis were performed by the same researcher (NF).\n\nThe liver was washed in physiological saline (0.9% NaCl) and immersed in a fixative solution (10% NBF). The histological preparation of the liver was carried out using the paraffin method of haematoxylin and eosin staining following Bancroft and Cook18 with the same steps as for kidney preparation. Histopathological scoring was performed using the ordinal post-examination masking method. Scoring was carried out in 100 fields per group using 40x objective lens magnification. Three parameters of damage, namely cellular damage, haemorrhage, and congestion were determined for the histopathological scoring system21–23 (Table 2). Liver sample fixation and histopathological analysis were performed by the same researcher (SEDN).\n\nAll measured data were analysed using the appropriate methods and without any exclusion. Data were analysed qualitatively and quantitatively. Qualitative data analysis was carried out descriptively. For quantitative data analysis, normality test was carried out first using the Shapiro-Wilk test (α=0.05). The scoring results were then analysed statistically using the Kruskal-Wallis test, which was followed by the Mann-Whitney test (α=0.05), since the data were not normally distributed, to find significant differences among the group (p<0.05). All data were analysed statistically using the SPSS version 16 (RRID:SCR_002865) program by the same researcher (NF).\n\n\nResults\n\nThe outcome of this research was the comparison of the histological characteristics of the kidney and liver under exposure to non-contact electric fields, which will be explained coherently in the sections below.\n\nThe effects of exposure to non-contact electric fields on renal histopathology and the ordinal scoring results of kidney damages are illustrated in Figure 1 and Figure 2, respectively. The main damage found in the kidney glomerular was the thickening of the Bowman capsule whose scores were significant in all treatment groups (1.12±0.56 for NIT, 1.16±0.74 for INT, and 1.24±0.59 for IT groups) compared to the control (NINT) group (0.88±0.56). In the kidney tubules, more damages were found, including karyolysis, karyorrexhis, pyknosis, cloudy swelling, and epithelial sloughing. However, the scores of these injuries were not significantly different among groups. In the kidney interstitial tissues, inflammation and haemorrhage were identified and the score of both damages in the placebo (NIT) group was the lowest (1.0±0.55) and significantly different to three other groups (1.19±0.51for NINT, 1.35±0.63 for INT, and 1.31±0.63 for IT groups). Congestion was found as a common injury in all parts of the kidney structure, and the number of congestions in the kidney structure of the placebo (NIT) group was also the lowest among treatment groups, but were not significantly different from the three other groups.\n\nKL=Karyolysis, KR=karyorrexhis, PK=pyknosis, CS=cloudy swelling, ES=epithelial sloughing, Co=congestion, In=inflammation, Hm=haemorrhage, TBC=thickening of Bowman’s capsule, NINT=non-induction and non-therapy group, NIT=non-induction and therapy group, INT=induction and non-therapy group, and IT=induction and therapy group.\n\n(a) Tubular damages, (b) interstitial damages, (c) glomerular damages, and (d) number of congestions.\n\nThe histopathological structure of the liver in the four groups had the same damage pattern but with different levels of damage as shown in Figure 3 and Figure 4. All groups had the same type of damage, namely cellular damage (pyknosis, karyolysis, karyorrhexis), haemorrhage and congestion, as well as reversible damage (cellular swelling and fatty change). No significant cellular damages were found after exposure to non-contact electric fields. Instead, the score of cellular injuries and hemorrhage was the highest after DMBA administration in INT group (1.96±0.51 and 0.88±0.46, respectively) and significantly different to control (NINT) group (1.75±0.43 and 0.63±0.48, respectively). The significant difference of hemorrhage score between IT group (0.87±0.56) and control (NINT) group (0.63±0.48),due to DMBA administration. Exposure to electric field in IT group slightly decreased hemorrhage, cellular injuries and congestion in liver (0.87±0.56, 1.82±0.48, 0.37±0.56, respectively) after DMBA administration as compared to INT group (0.88±0.46, 1.96±0.51, 0.52±0.66, respectively). The scores of congestion were also not significantly different among groups. The histology of the liver tissue in all groups did not show fibrosis, so it can be said that the congestion that occurred was not at a chronic level. Since there was no significant difference in the score of congestion among groups and fibrosis were not found, the congestion in all groups was still considered normal.\n\nHr=Haemorrhage, Cg=congestion, Pn=pyknosis, Kr=karyorrhexis, Kl=karyolysis, Cs=cell swelling, Fc=fatty change, NINT=non-induction and non-therapy group, NIT=non-induction and therapy group, INT=induction and non-therapy group, and IT=induction and therapy group.\n\n(a) Cellular damages, (b) haemorrhage, and (c) number of congestions.\n\n\nDiscussion\n\nIn the present study, the safety of the non-contact electric fields was revealed in the results of the histopathological analysis of kidney and liver in mammary tumour-induced rats, as discussed below.\n\nThe thickening of Bowman’s capsule as the main damage in the glomerulus (Figure 1) may be a result of glomerular hyperfiltration,24 nephrotoxicity caused by DMBA administration,25 and exposure to electric fields.26 Since the significant damages of the glomerulus were observed in the kidneys of the placebo (NIT), non-therapy (INT) and therapy (IT) groups, both DMBA administration and non-contact electric field exposure affected the thickening of Bowman’s capsule. Sharma and Paliwal27 reported that kidneys are one of the major target organs of DMBA (nephrotoxicity) and that the epithelial cells of Bowman’s capsule and the proximal convoluted tubules appear to be more susceptible to DMBA. Whereas the electric fields affected this damage by changing the transmembrane potential and distribution of ion channels and dipoles following changes in the membrane structure.28 Although both DMBA administration and exposure to non-contact electric fields affected the thickening of Bowman’s capsule, the individual toxicity effect of the electric field exposure was lower than the one with DMBA administration, as shown in Figure 2. Additionally, some biological effects of exposure to electric fields (0.6 and 340 kV/m) were revealed in humans and vertebrates, but no histological abnormalities were found in the organs, including the kidneys.29 Therefore, DMBA administration would have a greater risk of inducing renal impairment.\n\nThe nephrotoxicity effect of DMBA did not occur only in the glomerulus, but also in the tubules. Moreover, DMBA caused substantive nephrotoxicity that is depicted by renal tubular necrosis including karyolysis, karyorrexhis and pyknosis,30 as shown in Figure 1. Additionally, DMBA created obvious reversible histological changes in the tubules, such as epithelial sloughing and cloudy swelling, as illustrated in Figure 1. The epithelial sloughing represented the progressive disintegration of the tubules,29 and the cloudy swelling may lead to cell necrosis.4 However, since the score of each injury in the renal tubules was not significantly different among the groups, the nephrotoxicity effect of DMBA and the exposure to non-contact electric fields were not harmful to renal tubules. No reports have revealed necrosis or reversible injuries in renal tubules under exposure to the intermediate frequency and low-intensity electric fields, except exposure to 100 electric pulses resulting in high-intensity 575±67 V/cm electric fields for irreversible electroporation.31 Therefore, the exposure to intermediate frequency and low intensity non-contact electric fields was not harmful to the renal tubules.\n\nIn renal interstitial tissues, the nephrotoxicity effect of DMBA significantly caused inflammation and haemorrhage, as shown in Figure 2. This inflammation can be affected by oxidative stress and may induce renal function impairment, including endothelial dysfunction, atherosclerosis, and glomerular injury.32 Oxidative stress activates transcription factors including NF-kB, which activate the inflammatory response gene expression.33 Moreover, Kandeel et al.34 reported that oxidative stress may change the renal structure and function due to the effect of reactive oxygen species (ROS) on mesangial and endothelial cells. Oxidative injury happens when ROS, including O2, H2O2 and -OH, ruin the antioxidant defence systems of the cells.35 This ROS may be produced due to DMBA administration36 and it can spread from the site of production to other sites inside the cells or even extend the injury outside the cells.37 Additionally, de Oliveira et al.38 revealed that DMBA administration to develop a tumour in an animal model also causes haemorrhage. No reports have revealed inflammation and haemorrhage as well as congestion under exposure to intermediate frequency and low-intensity electric fields. Therefore, the exposure to non-contact electric fields was also not harmful to renal interstitial tissues. In fact, non-contact electric fields decreased the number of inflammations and haemorrhages in the placebo (NIT) group, as shown in Figure 2.\n\nAlmost the same as in kidney histology, there was no significant damage to the liver after exposure to electric fields (Figure 4). The results in the non-therapy (INT) group with the highest significant rate of hepatocellular damage and hemorrhage indicated that DMBA as a carcinogenic substance can increase the presence of intercellular haemorrhage in the hepatic tissue.23 Duarte et al.23 reported mild hepatotoxicity in the liver, including the presence of a pyknotic phase of nuclei of hepatocytes due to DMBA induction. However, haemorrhage in the hepatic tissue has not yet shown symptoms of acute haemorrhage, including cellular hypoxia, decreased tissue perfusion, organ damage, and death.39 The results in the therapy (IT) group with a lower rate of hepatocellular damage compared to the non-therapy (INT) one suggested that exposure to non-contact electric fields had lesser damaging effects than DMBA administration. Additionally, since the value of the congestion of blood vessels was still within the normal condition and not at the chronic level, the exposure to non-contact electric fields was not harmful. It was found that the intensity, frequency, and duration of exposure to non-contact electric fields and the dose of DMBA administered causes changes in the different parameters evaluated, although not very significant ones. However, these changes could be considered as a sign of metabolic alterations under the effect of the exposure to the non-contact electric fields and DMBA administration.\n\nBased on the evidence for the efficacy and safety of normal tissues and organs,8,9 including kidney and liver as reported in this study, we will be conducting a phase I clinical trial of ECCT for healthy volunteers using a 100 kHz 18 Vpp electric field as used in this study. Moreover, since this electric fields exposure may decrease the number of inflammations and haemorrhage in kidney, this therapy may be used to treat kidney injury or related diseases.40\n\n\nConclusions\n\nThe non-contact electric fields were not harmful to the renal and liver structure of tumour-induced rats. Instead, it may optimise the renal function in normal rats.\n\n\nEthical approval\n\nThis research was carried out at the LPPT UGM and at the Animal Structure and Development Laboratory of the Faculty of Biology, UGM. LPPT UGM has been awarded ISO/IEC 17025:2000 accreditation for competence in testing and calibration.11 Experimental protocol in this research was performed following approval by the Ethical Clearance Committee of LPPT UGM with ethical clearance number: 00015/4/LPPT/IV/2017, that has been previously reported.9 The Ethical Clearance Committee stated that this research met the ethical requirements for the study on experimental animals and that the Ethical Clearance Committee had the right to conduct monitoring during the research.",
"appendix": "Data availability\n\nOpen Science Framework: Kidney and liver histology in tumour-induced rats exposed to non-contact electric fields, https://doi.org/10.17605/OSF.IO/54BYF. 41\n\nThis project contains the following underlying data:\n\n‐ Kidney and liver histological images\n\n‐ Kidney scoring and statistical analysis\n\n‐ Liver scoring and statistical analysis\n\n‐ Kidney and liver charts\n\nOpen Science Framework: Kidney and liver histology in tumour-induced rats exposed to non-contact electric fields, https://doi.org/10.17605/OSF.IO/54BYF. 41\n\nThis project contains the following extended data:\n\n‐ Ethical clearance document\n\nOpen Science Framework: ARRIVE checklist for ‘Kidney and liver histology in tumour-induced rats exposed to non-contact electric fields’, https://doi.org/10.17605/OSF.IO/54BYF. 41\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nMany thanks to Sugianto and Fadlil for making the device performed in this study.\n\n\nReferences\n\nZhang Y, Ding J, Duan W, et al.: Influence of Pulsed Electromagnetic Field with Different Pulse Duty Cycles on Neurite Outgrowth in PC12 Rat Pheochromocytoma Cell. 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Histo. Histopathol. 2016; 3(1): 1–7. Publisher Full Text\n\nEl-Gerbed MSA: Silymarin, Protects Against 7,12Dimethyl-benz [A] anthracene–Induced Hepatotoxicity in Albino Rats. RJPBCS. 2013; 4(3): 1534–1548.\n\nElbaz A, Ghonimi WAM: Exposure Effects of 50 Hz, 1 Gauss Magnetic Field on the Histoarchitecture Changes of Liver, Testis and Kidney of Mature Male Albino Rats. J. Cytol. Histol. 2015; 06(4): 1–6. Publisher Full Text\n\nDuarte R, Jesus P, Farinha R, et al.: Adipose Tissue and Liver in DMBA Experimental Intoxication. Exp. Pathol. Health Sci. 2016; 8(1): 59:66.\n\nKotyk T, Dey N, Ashour AS, et al.: Measurement of the Glomerulus Diameter and Bowman’s Space Thickness of Renal Albino Rats. Comput. Methods Prog. Biomed. 2016; 126: 143–153. PubMed Abstract | Publisher Full Text\n\nPaliwal R, Sharma V, Pracheta, et al.: Anti-Nephrotoxic Effect of Administration of Moringa oleifera Lam in Amelioration of DMBA-Induced Renal Carcinogenesis in Swiss Albino Mice. Biol. Med. 2011; 3(2): 27–35.\n\nLee JS, Ahn SS, Jung KC, et al.: Effects of 60 Hz Electromagnetic Field Exposure on Testicular Germ Cell Apoptosis in Mice. Asian J. Androl. 2004; 6(1): 29–34. PubMed Abstract\n\nSharma V, Paliwal R: Chemo Protective Role of Moringa oleifera and Its Isolated Saponin Against DMBA Induced Tissue Damage in Male Mice: A Histopathological Analysis. Int. J. Drug Dev. Res. 2012; 4(4): 215–228.\n\nRems L, Kasimova MA, Testa I, et al.: Pulsed Electric Fields Can Create Pores in the Voltage Sensors of Voltage-Gated Ion Channels. Biophys. J. 2020; 119: 190–205. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPetri AK, Schmiedchen K, Stunder D, et al.: Biological Effects of Exposure to Static Electric Fields in Humans and Vertebrates: A Systematic Review. Environ. Health. 2017; 16(41): 1–23.\n\nSharma V, Paliwal R, Janmeda P, et al.: Renoprotective Effects of Moringa oleifera Pods in 7,12-Dimethylbenz [a]anthracene-Exposed Mice. J. Chin. Integr. Med. 2012; 10(10): 1171–1178. Publisher Full Text\n\nNeal RE, Garcia PA, Kavnoudias H, et al.: In Vivo Irreversible Electroporation Kidney Ablation: Experimentally Correlated Numerical Models. IEEE Trans. Biomed. Eng. 2015; 62(2): 561–569. Publisher Full Text\n\nCachofeiro V, Goicochea M, Vinuesa SG, et al.: Oxidative Stress and Inflammation, A Link Between Chronic Kidney Disease and Cardiovascular Disease. Kidney Int. 2008; 74: S4–S9. Publisher Full Text\n\nLi N, Karin M: Is NF-kappaB the Sensor of Oxidative Stress? FASEB J. 1999; 13(10): 1137–1143. Publisher Full Text\n\nKandeel M, Abdelaziz I, Elhabashy N, et al.: Nephrotoxicity and Oxidative Stress of Single Large Dose or Two Divided Doses of Gentamicin in Rats. Pak. J. Biol. Sci. 2011; 14: 627–633. Publisher Full Text\n\nKesba HH, El-Belagi HS: Biochemical Changes in Grape Rootstocks Resulted from Humic Acid Treatments in Relation to Nematode Infection. Asian Pac. J. Trop. Biomed. 2012; 2(4): 287–293. Publisher Full Text\n\nBharali R, Tabassum J, Azad MRH: Chemomodulatory Effect of Moringa oleifera, Lam, on Hepatic Carcinogen Metabolising Enzymes, Antioxidant Parameters and Skin Papillomagenesis in Mice. Asian Pac. J. Cancer Prev. 2003; 4(2): 131–139. PubMed Abstract\n\nKoul A, Arora N, Tanwar L: Lycopene Mediated Modulation of 7,12 Dimethlybenz(A) anthracene Induced Hepatic Clastogenicity in Male Balb/c Mice. Nutr. Hosp. 2010; 25(2): 304–310. PubMed Abstract\n\nde Oliveira KD , Avanzo GU, Tedardi MV, et al.: Chemical Carcinogenesis by DMBA (7,12-Dimethylbenzanthracene) in Female BALB/c Mice: New Facts. Braz. J. Vet. Res. Anim. Sci. 2015; 52(2): 125–133. Publisher Full Text\n\nGutierrez G, Reines HD, Wulf-Gutierrez ME: Clinical Review: Hemorrhagic Shock. Crit. Care. 2004; 8: 373–381. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen W, Wang L, Liang P, et al.: Reducing ischemic kidney injury through application of a synchronization modulation electric field to maintain Na+/K+-ATPase functions. Sci. Transl. Med. 2022; 14(635): eabj4906. Publisher Full Text\n\nAlamsyah F: Kidney and Liver Histology in Tumour-induced Rats Exposed to Non-contact Electric Fields. [Dataset]. OSF. 2022 October 22. Publisher Full Text"
}
|
[
{
"id": "162015",
"date": "27 Feb 2023",
"name": "Chandran Nadarajan",
"expertise": [
"Reviewer Expertise Interventional oncology",
"interventional and diagnostic radiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nEditorial Note from F1000Research – 06/03/2023:\nThis report has been updated after the reviewer informed the editorial team that they had further comments after their initial review was published. The changes are due to some factors which were not assessed in the initial review and were picked up when the reviewer read the article again. This update has not changed the ‘Approved’ status that the reviewer originally assigned.\nThis study touches on the effect of a new technology being introduced in oncology and answers some of the questions regarding the safety issue of the device. This information is critical to further utilize this device in the general public.\n\nSome additional information from the authors could elevate the write-up:\nWhy do the authors choose the voltage 100kHz and 18v, specifically? Were the preliminary results referred to published? Are there any other articles supporting the usage of this voltage and frequency?\n\nIs there any statistical analysis done? This will help strengthen the conclusion.\n\nWhy was there damage in the kidney interstitial tissue and liver damage in the NINT group?\nIn addition, some of the articles referred to use different voltage and frequency levels; therefore, it couldn't be a direct comparison of this study. Such correlation needed to be taken with caution.\nOverall, this study tries to answer the safety aspect of this non-contact electrical field therapy and highlights some promising changes.\n--------------------------------------------------------------------------\nFirst of all, I maintain that the paper is quite impressive and constructive with a novel idea. However, I would suggest a few additional points:\nFigures 1 and 3 are very small, with many icons. Please enhance them.\n\nFigures 2, and 4 suggest changing to the Whisker box plot and being made bigger. It will be better.\n\nUtilization of rank order, like Mann Whitney, might help to bring forward the idea better.\n\nConclusion is a little too short and needs to be improved. Adding limitations and further direction might help. This can be done in the discussion.\n\nIRB date, number, and place should be shown.\n\nIn several places, language is unclear, ambiguous, or confusing. It is necessary to use a professional editing service to improve it before indexing.\n\nI think the title \"Effects of non-contact electric fields on kidney and liver histology in tumour-induced rats.\" Might be more appropriate.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9411",
"date": "01 Mar 2023",
"name": "Firman Alamsyah",
"role": "Author Response",
"response": "I will answer the reviewer's comments sequentially in the order of the comments. 1. We have conducted an in vitro study using various frequencies and intensities, but this study has not been published. We used 100 kHz and 18 Vpp for in vivo study because this frequency and intensity gave the best results in in vitro study, where 28-39% of breast cancer cells died (Alamsyah et al., 2015). In the preliminary in vivo study using 9 mice, the frequency of 100 kHz and intensity of 18 Vpp also gave good results, where the tumor size was reduced by more than 67% and the results of histopathological analysis on normal skin and breast tissue, showed no damage (Alamsyah et al., 2015). 2. Yes, we did the statistical analysis and it has been written in the article in the Data Analysis section. Kidney and liver scoring data, as well as statistical analysis can be seen in the links provided in the Data Availability section of the article. 3. Damage to the kidneys and liver of the rats in the control group (NINT) cannot be predicted, because we have excluded rats with symptoms of illness as stated in the article. Rats were also randomly selected for each group as stated also in article. For damage in the renal interstitial tissue of the NINT group, a score below 2 indicated that there was little inflammation or hemorrhage. Inflammation is part of the activation of the immune system in response to acute or chronic kidney injury which can be caused by pathogens that enter the rat’s body (Imig & Ryan, 2013). For damage in the liver of the NINT group, if we look at the hemorrhagic and congestion scores which are below 1, this indicated that there was little or no damage to the liver. For a cellular damage score below 2, this indicated reversible damage with less than 15% necrosis. Liver hepatocytes have many vital functions, so they can proliferate extensively, which allows efficient regeneration of the liver for reversible damage (Chen et al., 2020). In addition, the liver itself is a very vulnerable organ due to its size and is the organ most frequently injured after abdominal trauma (Bilgic et al., 2014). Rats are active animals and may chase or fight each other in communal cages which can cause trauma to their body (Steimer, 2011). 4. We found no reference to kidney or liver damage at intermediate frequency and low intensity electric fields, especially 100 kHz and 18 Vpp. We have also stated this in the article. In the Introduction section, we have also stated that this is the first study to investigate abnormalities in the kidney and liver under exposure to a intermediate frequency of 100 kHz and a low intensity non-contact electric field. We will add necessary information to our article from the answers to the reviewer's questions. Thank you. References Alamsyah F, Ajrina IN, Dewi FN, et al.: Antiproliferative Effect of Electric Fields on Breast Tumor Cells In Vitro and In Vivo. Indones. J. Cancer Chemoprev. 2015; 6(3): 71–77. Bilgiç I, Gelecek S, Akgün AE, et al.: Evaluation of liver injury in a tertiary hospital: a retrospective study. Ulus Travma Acil Cerrahi Derg. 2014; 20(5): 359-365. Chen F, Jimenez RJ, Sharma K, et al.: Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration. Cell Stem Cell. 2020; 26(1):27-33 Imig JD, Ryan MJ: Immune and Inflammatory Role in Renal Disease. Compr. Physiol. 2013; 3(2): 957-976. Steimer T: Animal models of anxiety disorders in rats and mice: some conceptual issues. Trans Res. 2011; 495-506."
},
{
"c_id": "9486",
"date": "21 Mar 2023",
"name": "Firman Alamsyah",
"role": "Author Response",
"response": "We thank you for the additional suggestions and we will revise our paper. Below are our answers to the suggestions provided in order. 1. We will enhance Figure 1 and Figure 3 in our revision. 2. We will consider to use the Whisker box plot in Figure 2 and Figure 4. 3. We have conducted Mann-Whitney test (α=0.05) in our statistical analysis. 4. We will improve the conclusions of our study and we will discuss the limitations of this study. We have written further directions of this study at the end of the discussion section. 5. IRB date, number, and place have been written in the ethical approval section. 6. We have used a professional editing service (PaperTrue) before submitting this article. We will do one more proofreading. 7. We will improve the title of this article."
}
]
},
{
"id": "162014",
"date": "02 Mar 2023",
"name": "Michael Staelens",
"expertise": [
"Reviewer Expertise Electromagnetic interactions with biological systems",
"microtubules",
"biophysics",
"high energy physics",
"particle physics."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript, “Kidney and liver histology in tumour-induced rats exposed to non-contact electric fields”, by Alamsyah et al., reports new results on the effects of 100 kHz low-intensity non-contact electric fields on the histological profiles of kidney and liver samples taken from Sprague Dawley rats exposed to such fields (with and without tumour induction). Alternating electric fields with these particular parameters (low intensity and intermediate frequency) have become topical in oncology, especially over the last decade, due to the earlier discovery that these fields (also known as TTFields) greatly hinder the division of cancer cells. Several successful clinical trials on treating different types of cancer with TTFields have led to the subsequent FDA-approval of TTFields therapy for various cancers, such as glioblastoma. Consequently, many in vivo and in vitro studies on the efficacy of alternating electric field therapy have been conducted; however, safety studies are lacking in number and should grow in tandem with the efficacy studies. Thus, the study reported in the manuscript by Alamsyah et al. is both interesting and valuable to the scientific community (and a cancer research audience in particular); however, substantial major issues with the manuscript make the conclusions and, ultimately, the value and impact of the study uncertain. While I do believe the study has potential, the authors must revise the manuscript substantially before it should be indexed. Particularly, the literature review with regards to the Introduction and Discussion sections needs to be revisited and refocused; the statistical analysis used to determine the significance of the results does not apply, and a new analysis is required; and the very limited and overly general conclusions that do not appear to follow from the results and discussion presented in the manuscript must be stated more clearly to accurately reflect the results of the study. A complete list of my comments and concerns that must be addressed, both general and specific, are provided below.\nGeneral Comments:\nThere are many problems with the writing regarding grammar, punctuation, missing spaces, article usage problems, misspelled words, incorrect verb forms, faulty tense sequences, incomplete sentences, and several other sentences that simply do not make sense. In aggregate, these errors severely hinder the readability and clarity of the manuscript. I strongly recommend that the authors consider sending the manuscript to a professional English editing service, or at the very least, use one of the numerous free grammar and writing tools available online to assist with correcting many of the writing issues.\n\nThe manuscript mixes both U.S. and U.K. spellings, e.g., “tumor” and “tumour” are both used, as are “acclimatization” and “randomisation” (z vs. s). Please maintain one choice consistently in your writing.\n\nThe manuscript lacks coherence and does not communicate a cohesive story. Here are some examples of inconsistencies that negatively affect the cohesion:\n- In the “Results” part of the Abstract, it reads, “The damages in the kidney and liver caused by the exposure were not significant.”, but then in the Discussion section, the following is stated “Since the significant damages of the glomerulus were observed in the kidneys of the placebo (NIT)…”, followed by, “both DMBA administration and exposure to non-contact electric fields affected the thickening of Bowman’s capsule”, which certainly sounds like there were significant damages observed in the kidney samples taken from the group that only received exposure to the electric fields (NIT).\n- The need for studying the effects of electric fields-based cancer therapies on healthy tissues was motivated in the Introduction by pointing out that there might be interactions between the kidney/liver and electrostatic waves; however, the electric fields-based cancer therapies referenced and discussed in the manuscript (and that are actually used in a clinical setting) do not employ static fields, but rather alternating electric fields.\n- Several of the references cited in the Discussion section that are discussed with regards to the interpretation of the results studied vastly different parameters for the electric fields than those employed in the experiments reported in the manuscript and that are typically used to treat cancers with alternating electric field therapy (e.g., 575 V/cm in one of the studies cited vs. the low-intensity of only a few V/cm maximum for alternating electric field therapy).\n\nThe manuscript often mentions the significance of results/effects; however, none of these statements include the supporting quantitative results that suggest the differences obtained are, in fact, significant (or not). Consequently, the level of significance associated with these statements is also not clear to the reader (without reading through the data files provided alongside the manuscript). Please revise all these statements to include the quantitative results of the statistical analyses that support the stated significances. For example, the following sentence on page 5, “The main damage found in the kidney glomerular was the thickening of the Bowman capsule whose scores were significant in all treatment groups (1.12±0.56 for NIT, 1.16±0.74 for INT, and 1.24±0.59 for IT groups) compared to the control (NINT) group (0.88±0.56).”, should be revised to include the corresponding H-values (or p-values, etc.) that supports the statement that these differences between scores were significant (“in all treatment groups compared to the control group”). This makes it both clear to the reader that the differences between groups are indeed significant based on the statistical analysis results obtained and provides the reader with the quantitative results, so they also get a sense of how significant (or insignificant) each particular result is without having to dig through spreadsheets of data while reading the article.\n\nThe quality of the plots provided in Figures 2 and 4 is quite low. Additionally, the dots used to represent the data are very small and difficult to distinguish (when reading the article on a tablet at 100% magnification). Please consider reproducing these plots at a higher quality (600 DPI or greater) and with the points used to represent the data enlarged and spread out more clearly, so the individual points are distinguishable without needing to zoom in (which also leads to substantial blurring due to the low quality of the plots).\nSpecific Comments: Major concerns:\nThe data analysis section states that the scoring results were analyzed statistically using the Kruskal–Wallis test; however, the scoring results were obtained for four different groups that differed independently in two ways (i.e., there were two independent variables involved—tumour induction (or not) and treatment (or not)). Consequently, the Kruskal–Wallis test, which is only applicable in the one-factor case, cannot be used. Due to this problem, the actual statistical significance of the obtained differences between the various groups studied is not clear, and the soundness of the conclusions drawn is uncertain. If you do require a non-parametric rank-based method, then consider the Scheirer–Ray–Hare extension of the Kruskal–Wallis test, which can be used in the case where a measure may be affected by two or more factors. Alternately, the (two-factor) aligned rank transform analysis of variance (ART-ANOVA) may also be suitable.\n\nMoreover, the conclusions do not appear to be clearly supported by the results. This concern is not only due to the previous major comment noted but also due to the following:\n- The first conclusion drawn is that “The non-contact electric fields were not harmful to the renal and liver structure of tumour-induced rats\"; however, one of the outcomes described in the Results and Discussion sections was that the non-contact low-intensity electric fields significantly \"affected the thickening of Bowman's capsule\" (NINT versus NIT), which is apparently indicative of renal damage. Consequently, I am not sure that this general conclusion is completely supported by the results of this study.\n- The second conclusion drawn is that non-contact electric fields “may optimise/increase the renal function in normal rats”. What results obtained in this study demonstrate an optimization and/or increase in renal function in normal rats exposed to low-intensity non-contact electric fields? The only discussion in the manuscript regarding renal function appears to be that provided on page 8; however, the discussion there mentions renal function impairment as a possible result of DMBA-induced inflammation and does not discuss electric fields. At the end of this paragraph, non-contact electric fields are mentioned: “non-contact electric fields decreased the number of inflammations and haemorrhages in the placebo (NIT) group, as shown in Figure 2”; however, the statistical significance of this difference is not stated. Is the decrease being mentioned here actually meaningful statistically? And if so, how statistically significant was this decrease, and how exactly does this marginal decrease in observed inflammations and haemorrhages connect to the conclusion that renal function has been optimized due to treatment with non-contact electric fields? As far as I can tell, no tests or metrics that could be used to accurately evaluate any changes in kidney and/or liver function and that would support this particular conclusion were included in the experiments and analyses reported in the manuscript.\n\nWhy were damages also exhibited in the control (NINT) group? Naively, I would not have expected this outcome, and it is not explained or discussed in the manuscript.\nDue to these major concerns, I do not believe that the conclusions stated in the manuscript are clearly supported by the results.\nMinor concerns:\nMore details regarding both the electric field used in the experiments and how it was applied should be provided for clarity and reproducibility of the study:\n- How were the electric fields generated? What device was used (make, model, etc.)?\n- Were the electric fields static or alternating?\n- What was the duty cycle?\n- Given that the rats were exposed to non-contact electric fields, I assume that the electrodes were not fixed to the skin of the rats and that they received whole-body exposure to the electric fields. Is this true? Additionally, how many electrodes were used? where were they placed/attached? and with what orientation? In other words, how many electric fields were there, were they uniform or non-uniform, and with what directionality(ies)?\n\nPlease provide this information in the manuscript.\n\nWhile the exposures were being performed, were there any other sources of electromagnetic radiation in the room that could be considered a source of interference?\n\nOn page 3, the last sentence in the Introduction states, “According to our knowledge, this is the first study investigating the abnormalities in the kidney and liver under exposure to 100 kHz intermediate frequency and low-intensity non-contact electric fields”, which does appear to technically be true; however, a very similar1 study was recently published that reports the results of analyzing histological profiles of vital organs of Sprague Dawley rats exposed to 150 kHz low-intensity non-contact electromagnetic radiation. It would be valuable and interesting to revise the discussion in the manuscript to compare and contrast your results and conclusions obtained versus those reported in this very similar study in the literature.\n\nOn page 3, a value of 18 Vpp is noted after stating that the electric fields used in the study are low intensity. The electric field intensity has units of electric potential per distance (V/m in SI units), not simply volts, which is the unit of electric potential. Please revise accordingly (including at the bottom of page 3, where the same issue occurs again).\n\nOn page 3, it is stated that “Although non-contact electric fields-based therapy has the potential to treat cancer, the safety of this kind of therapy when treating healthy tissues should be investigated. This is because injuries may occur after exposure to electric fields due to the dielectric property of the kidney and liver, which may interact with electrostatic waves. Therefore, it is important to investigate the abnormalities in the kidney and liver under exposure to electric fields during cancer treatment.” The second sentence quoted here does not connect to the previous or subsequent sentences; the electric fields used in cancer treatment that this article alludes to, so-called TTFields, are alternating electric fields (time-varying), whereas electrostatic always refers to time-invariant electric fields. Please revise.\n\nAdditionally, on page 3, the sentence “the proliferation of cancer cells was successfully inhibited under exposure to intermediate frequency and low-intensity electric fields” should be revised to read “low-intensity alternating electric fields”. This statement would also benefit from more specificity, i.e., what types of cancer cells was this inhibition demonstrated for in the studies cited here and with what parameters for the electric fields employed (frequency, intensity, duration of exposure)?\n\nShould the y-axis label for Figure 2d read “Congestion score” instead? (To maintain consistency with the other subfigures presented in Figure 2 and with Figure 4c.)\n\nIn Figure 4, the values of mean ± SD noted in each of the subfigures use inconsistent numbers of significant digits. Specifically, the values of the uncertainties are reported with greater precision than the mean values themselves, which indicates that the errors are known more precisely than the values and is very unusual.\n\nFigures 2 and 4 include a footnote partially describing the meaning of the labels “a”, “b”, etc. as indicating significance; however, the difference between each of these labels is not clear. The exact meaning of “a”, “b”, etc. should be clarified in the notes provided under Figures 2 and 4. Additionally, while it is clear that, for example, in Figure 2a, the NINT group has the label “a” to denote that it is significant, it is not clear what it is being compared to, i.e., significant compared to which group(s)? Lastly, please change “different words a, b, c” to read “different letters” or “different labels”.\n\nIn the second paragraph of the Discussion on page 7, it is mentioned that “some biological effects of exposure to electric fields (0.6 and 340 kV/m) were revealed in humans and vertebrates, but no histological abnormalities were found in the organs, including the kidneys.” Comparing with this study does not make much sense for the following reasons:\n- The particular study cited here evaluated the biological effects of static electric fields, which are not the same as the alternating electric fields exploited in cancer therapy, and that the manuscript purportedly studies the effects of.\n- The parameters stated (0.6 and 340 kV/m) corresponding to this particular study that is being referenced are NOT consistent with the low-intensity electric fields used in cancer therapy (approx. 1–3 V/cm) and, again, that the manuscript appears to be studying.\n\nThe abbreviation ECCT is not defined anywhere in the manuscript.\n\nThe first sentence in the last paragraph of the Discussion section (page 9) does not make sense. Specifically, what does “Based on the evidence for the efficacy and safety of normal tissues and organs...” mean? I believe that rather than describing evidence on the “efficacy and safety of a normal tissue”, what is trying to be said here is something like, “Based on the evidence for the efficacy and safety of non-contact low-intensity electric fields regarding normal tissues and organs...”, or something along these lines. Please rephrase this sentence accordingly.\n\nThe statement regarding the role of the funders, “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”, should also mention the role of the funders regarding the interpretation of the data/results.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9496",
"date": "23 Mar 2023",
"name": "Firman Alamsyah",
"role": "Author Response",
"response": "We thank you for all the comments and suggestions and we will revise our paper. Below are our answers to the comments and suggestions provided in order. General comments 1. We have used a professional English editing service (PaperTrue) before submitting this article. We will do one more proofreading. 2. We will use UK spelling in our revised article. 3. We will revise the abstract so that it is coherent with the contents of the paper. We will replace some of the references in the Discussion section. Previously, we did not find any references in accordance with the study conducted. 4. In the Data Analysis section and in the Figures, we have mentioned a p<0.05 value for a significant difference among groups. We will rewrite it for each data in the Results section. 5. We will fix Figures 2 and 4. Specific comments Major concerns 1. We will evaluate the statistical tests performed. 2. We will revise the Conclusions section to suit the Results and Discussion sections. 3. Damage to the kidneys and liver of the rats in the control group (NINT) cannot be predicted because we have excluded rats with symptoms of illness as stated in the article. Rats were also randomly selected for each group as stated also in article. For damage to the kidney in the NINT group, if we look at the interstitial tissue, a score below 2 indicates that there is little inflammation or hemorrhage. Inflammation is part of the activation of the immune system in response to acute or chronic kidney injury which can be caused by pathogens that enter the rat’s body (Imig & Ryan, 2013). For damage to the liver in the NINT group, if we look at the hemorrhagic and congestion scores which are below 1, this indicates that there is little or no damage to the liver. For a cellular damage score below 2, this indicates reversible damage with less than 15% necrosis. Liver hepatocytes have many vital functions, so they can proliferate extensively, which allows efficient regeneration of the liver for reversible damage (Chen et al., 2020). In addition, the liver itself is a very vulnerable organ due to its size and is the organ most frequently injured after abdominal trauma (Bilgic et al., 2014). Minor concerns 1. We will provide more detailed information about the electric fields used in the experiment in our revised article. 2. The experiment was carried out in a special room which only contained experimental animal cages. 3. We will revise the Discussion section using the appropriate references. 4. We will include electric fields intensity data in our revised article. 5. We will revise this section (page 3). 6. We will revise this section (page 3). 7. We will revise Figure 2d. 8. We will revise Figure 4. 9. We will revise Figures 2 and 4. 10. We will revise the Discussion section using the appropriate references. 11. We will write what ECCT stands for in our revised article. 12. We will rephrase this sentence. There may be phrases lost in the editing process. 13. We will add the statement regarding the role of the funders in the interpretation of the data/results. References Bilgiç I, Gelecek S, Akgün AE, et al.: Evaluation of liver injury in a tertiary hospital: a retrospective study. Ulus Travma Acil Cerrahi Derg. 2014; 20(5): 359-365. Chen F, Jimenez RJ, Sharma K, et al.: Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration. Cell Stem Cell. 2020; 26(1):27-33 Imig JD, Ryan MJ: Immune and Inflammatory Role in Renal Disease. Compr. Physiol. 2013; 3(2): 957-976."
}
]
}
] | 1
|
https://f1000research.com/articles/12-117
|
https://f1000research.com/articles/13-822/v1
|
23 Jul 24
|
{
"type": "Research Article",
"title": "Analysis of internet educational websites on tobacco cessation: A content analysis",
"authors": [
"B R Avinash",
"Kaveri Chengappa",
"Ramya Shenoy",
"Ashwini Rao",
"Mithun Pai",
"G Rajesh",
"B R Avinash",
"Kaveri Chengappa",
"Ramya Shenoy",
"Ashwini Rao",
"G Rajesh"
],
"abstract": "Background There have been significant changes in the lifestyles of individuals in the past few decades, which has led to increased morbidity and mortality worldwide. Both smoking and chewing forms of tobacco are highly prevalent, especially in India, and are implicated as causes of diseases, including oropharyngeal carcinomas. Effective tobacco cessation techniques and sources can help overcome addiction and reduce the disease burden in society. The aim was to evaluate the quality and readability of contents of various sources on an internet website about tobacco cessation.\n\nObjectives i) To evaluate the readability of internet content (Google) regarding tobacco cessation using Flesch–Kincaid readability tests and the quality of internet content (Google) by using the JAMA benchmark, HONcode and DISCERN questionnaire.\n\nMethods A content review was employed to screen the content of the Google search engine for educational tobacco cessation websites, and the top 50 websites were selected according to criteria and reviewed by two reviewers. The readability of the internet content (Google) regarding tobacco cessation was evaluated using Flesch–Kincaid readability tests. The quality of the screened sites was evaluated by using the JAMA benchmark, HONcode and DISCERN questionnaire, and the readability and quality of the screened websites were correlated using the above instruments.\n\nResults FK readability ease was found to be 49% standard and 30% easy. The FK grade test found that 33% of the content could be easily understood by < 5th grade. All 4 JAMA benchmarks were met by 23% of websites, and authorship was the least fulfilled criterion. Correlation analysis revealed a significant association between FK ease score and FK grade score.\n\nConclusions The Read-ability Ease and Read-ability Grade Levels of the websites related to tobacco cessation were not standard, and few websites fulfilled the JAMA benchmarks and had HONcode certification.",
"keywords": [
"Oral cancer",
"Oral health",
"Online resources",
"readability tests",
"Smokeless tobacco",
"Tobacco cessation"
],
"content": "Introduction\n\nThere have been significant changes in the lifestyles of individuals in the past few decades, which has led to increased morbidity and mortality worldwide.1 Habits such as tobacco use, alcohol, diet and other lifestyle factors have been implicated as cause of diseases such as cancers of the body, including oropharyngeal cancer.2–4 The disease burden is higher in underdeveloped and developing countries than in their economically stable counterparts. The hallmark of these diseases is their preventability. With effective motivation and implementation of programs aimed at tobacco control, the burden of such deadly diseases can significantly be decreased. Effective tobacco cessation techniques and sources can help overcome addiction and reduce the disease burden in society.5,6\n\nRecent decades have also witnessed a substantial rise in the number of individuals using mobile and smartphones and, with it, the internet. Everyone with a smartphone now has easy access to information on the internet, which can have a significant impact on an individual’s lifestyle.7 Regardless of the background of individuals, they can now browse the internet for information related to various health-related issues and conditions.8,9\n\nVarious web resources can provide information about tobacco cessation to general population.7 This raises concerns about the quality of information on tobacco cessation and the contents of the same information on the internet, which may or may not be optimal, credible and standardized. There are very few investigations reported in the literature that have explored the content, quality and readability (comprehensibility) of internet resources on tobacco cessation. They can provide valuable information paving the way for standardizing this content on tobacco cessation on various websites, which are specifically tailored to reach common men.\n\nHence, the aim of the present study was to evaluate the quality and readability of the contents of various resources on internet websites about tobacco cessation. Objectives: i) To evaluate the readability of internet content (Google) regarding tobacco cessation using Flesch–Kincaid readability tests. ii) Evaluate the quality of the internet content (Google) regarding tobacco cessation by using the JAMA benchmark, HONcode and DISCERN questionnaire.\n\n\nMethods\n\nThe present study was performed using a review of the internet content on tobacco cessation. Google, a common search site, was deployed to search for content on tobacco cessation. Fifty websites that appeared first on the specific day were reviewed for their content, readability & quality. The inclusion criteria were websites that are patient focused and websites that do not involve any cost or subscription. Websites that were password protected and contained only videos and journals were excluded.\n\nSelected websites after screening were evaluated for their quality, content and readability. Flesch–Kincaid readability tests10,11 evaluated the readability of the internet source. Flesch–Kincaid readability tests include Flesch readability ease and Flesch–Kincaid grade level. The JAMA benchmark,12,13 HONcode,13,14 and DISCERN questionnaire were used to assess website quality.15\n\nEthical approval was obtained prior to the study process from Institutional Ethics Committee. (Protocol ref no. 19051).\n\nThe parameters were entered in excel sheet and Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc, Chicago IL).16 P value <0.05 was considered to be significant. Mean was used for descriptive data. Percentage was used to interpret FK readability tests. Mean and median was taken for DISCERN-16 questionnaire. Student’s t test was employed to evaluate HONcode Scores with DISCERN tool and FK readability scores. Pearson’s correlation was done to assess the relationship between DISCERN, FK scores and HONcode values.\n\n\nResults\n\nForty-three websites were reviewed. Seven websites were not included because they did not fulfil the inclusion criteria; hence A total of 21 (49%) websites were of standard Readability with an Ease Score of the Flesch–Kincaid readability test. Overall, 13 (30%) websites had a fairly easy readability ease score. Readability Grade Level analysis of the Flesch–Kincaid readability test indicates that a majority of 14 (33%) websites could be read by individuals lower than 5th grade, while 13 (30%) websites could be read by individuals belonging to 6th grade. A total of 5 (12%) websites could be read by individuals belonging to 8th grade (Table 1).\n\nThe findings of the current study indicate that a total of 10 (23%) of the websites satisfied all 4 JAMA benchmarks. Overall, the number of websites satisfying 1, 2 and 3 of the JAMA benchmarks was 6 (14%), 7 (16%) and 19 (44%), respectively. A total of 41 (95%) websites satisfied the JAMA benchmark of disclosure, while a total of 15 (35%) websites satisfied authorship criteria. It was also observed that a total of 8 (19%) websites did not have HONCODE certification, while a total of 35 (81%) websites had HONCODE certification.\n\nThe median and mean scores for questions in DISCERN-16. It can be observed that the mean score was maximum for item number 1 and was minimum of 2.91 for item numbers 5, 6 and 8. A majority of 21 (49%) of the websites as assessed by DISCERN-16 belonged to the fair category, while none of the websites belonged to the very poor and excellent categories.\n\nThe results of the correlation analysis indicate that there were significant associations between HonCODE certification and DISCERN total scores (p=0.021), DISCERN S1 (p=0.033) and DISCERN S2 (p=0.021). It can also be observed that there were statistically significant associations between DISCERN-S1 and DISCERN-S2, DISCERN-S1 and DISCERN-S3, DISCERN-S1 and DISCERN-16 total, DISCERN-S2 and DISCERN-S3, DISCERN-S2 and DISCERN-16 total, DISCERN-S3 and DISCERN-16 total. There were also statistically significant associations between HonCODE certification and DISCERN S1, DISCERN-S2 and DISCERN-16 total scores. Additionally, significant associations were found between FK ease and FK grade scores (Table 2).\n\n* Significant at 5 % level of significance.\n\n** Significant at 1% level of significance.\n\n\nDiscussion\n\nThere have been significant advancements in the field of information technology and mobile phone services. These developments are very dynamic and are witnessing tremendous growth every passing day.9\n\nThe present study employed F–K readability, consisting of Flesch ease and grade level in place of a similar index such as the SMOG index. One of the issues with the use of the SMOG index has been its tendency to forecast readability 2 grades higher than the other estimates. The SMOG index depends upon the strict criteria of 100% accurate answers by participants. The findings of the current study indicate that the Ease Score was standard and fairly easy for the majority of the content included in the study. The current study contrasts with those reported by Wiriyakijja et al.,17 for websites on oral leukoplakia and Diniz-Freitas et al.,18 for tobacco cessation net-contents.\n\nMaterial in the current study was primarily readable by individuals lower than 5th grades and in agreement with the study conducted by Joury et al.19 The National Institutes of Health recommended readability age is between 7th and 8th grades. However, reduced reading grades lead to dilution of contents.\n\nThe results of the present study indicate that 23% of the websites fulfilled all the JAMA benchmarks. In a similar study conducted by Wiriyakijja et al., it was noted that 17% of websites on oral leucoplakia fulfilled all four JAMA benchmarks,17 and Ni Riordain et al., observed that 45% of websites on head and neck cancer fulfilled all four JAMA benchmarks.20 Diniz-Freitas et al.,18 who observed that none of the websites related to tobacco cessation services by dentists fulfilled all 4 JAMA benchmarks. A majority of the JAMA benchmarks fulfilled in the present study include disclosure (95%) and attribution (79%). The findings are in concordance with those reported by Wiriyakijja et al.,17 for websites on oral leucoplakia but in disagreement with those observed by Diniz-Freitas et al.,18 for websites on tobacco cessation services by dentists. Authorship and currency were the frequently fulfilled JAMA benchmark in websites on adult orthodontics, as reported by McMorrow et al.21\n\nIt can also be observed that 81% of the sites lacked HONcode certification, which is in agreement with those observed by Wiriyakijja et al., Diniz-Freitas et al.,,18 and Joury et al.19 and in disagreement with the reports of McMorrow et al.21 It has been reported by Ni Riordain et al., that 39% of websites had HON code seals.20 HON code assesses ethics and reputation rather than quality and information.\n\nThe number of subjects browsing internet sources for health information has considerably increased in the recent decade.22 This finding sheds light on the importance of the ease and readability of available content.17 Reliability of information in the field of oral cancer in different languages is also not standardized.23\n\nReading readily available internet content pertaining to tobacco increases anxiety due to the realization of unmet health needs.24 Increased levels of anxiety may also be related to poor health outcomes, and low compliance with treatment regimens and instructions. Therefore, there is a definite need for accurate information related to tobacco cessation on the internet.\n\nVarela-Centelles et al., observed that the overall quality for oral cancer in health care professionals (HCP) addressed websites were of good standards.25 There needs to be a consensus on what constitutes good information for patients who are seeking information on the internet on tobacco cessation.\n\nOn the other hand, it can be observed that there is information overload on the internet, and there can be information that is conflicting in nature.26 The subjects need to be sensitized about the issues related to information overload, such as dubious information sources and the availability of too much information for one’s perusal. Patients may specifically be interested in the treatment outcomes associated with tobacco cessation services in particular. This may shape the patients’ expectations to be more realistic in nature, and the patients may be more receptive of various treatment outcomes.27\n\nVarious factors might influence the diverse nature of information available on the internet. Various websites are fabricated by a wide variety of individuals hailing from diverse philosophical backgrounds. The purpose of website preparation may also be very different. Moreover, health literacy levels, and access to the internet may vary among patients.\n\nLimitations of the present study will have to be borne in mind. The cross-sectional design of the study and the inclusion of a limited number of websites are its limitations. Internet content is very dynamic and is constantly changing by day. Further studies that consider a greater number of websites need to be conducted. The assessment of the content of the websites was performed by using a checklist prepared specifically for the present study. All the issues related to tobacco cessation may not be encompassed by this checklist. The websites excluded in the present study might be viewed by the patients. The present study also excluded scientific articles and books, which might be good sources of accurate information. The websites were evaluated by a dentist who was qualified and specifically trained for the purpose of the study. This type of dentist might have greater knowledge than those who check the websites. The trained dentist may also be more critical in analysing the contents of the websites than the common person.\n\n\nConclusions\n\nIt can be observed that the read-ability ease and read-ability grade levels of the websites related to tobacco cessation were not up to the mark. Very few websites fulfilled all the JAMA benchmarks and had HONcode certification. There is a definite need for stricter rules and regulations for websites providing information related to tobacco cessation. There is a need for policy change to reinforce stricter regulation.\n\nEthical clearance was obtained from the Institutional Ethics Committee of Manipal College of Dental Sciences, Mangalore (Ref No. 19051).\n\nInformed consent: Ethical committee permission was taken and was exempted (Ref No. 19051).",
"appendix": "Data availability\n\nFigshare: Analysis of internet Educational websites on tobacco cessation health sciences. https://doi.org/10.6084/m9.figshare.24933876. 28\n\nThis project contains the following underlying data:\n\n- EQIP (2).xlsx\n\n- How to quit tobacco (2).xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nNaghavi M, et al.: Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 385: 117–171. Publisher Full Text\n\nPetersen PE, Bourgeois D, Ogawa H, et al.: The global burden of oral diseases and risks to oral health. Bull. World Health Organ. 2005 Sep; 83(9): 661–669. PubMed Abstract\n\nPetersen PE: World Health Organization global policy for improvement of oral health-World Health Assembly 2007. Int. Dent. J. 2008; 58(3): 115–121. PubMed Abstract | Publisher Full Text\n\nPetersen PE: Global policy for improvement of oral health in the 21st century-implications to oral health research of World Health Assembly 2007, World Health Organization. Community Dent. Oral Epidemiol. 2009; 37(1): 1–8. PubMed Abstract | Publisher Full Text\n\nSiegel R, Ma J, Zou Z, et al.: Cancer statistics, 2014. CA Cancer J. Clin. 2014; 64(1): 9–29. PubMed Abstract | Publisher Full Text\n\nInternational Telecommunications Union: The World in 2014: ICT Facts and Figures. Accessed on April 26, 2022. Reference Source\n\nSmoke free: Quitting is a Journey. Accessed on 26th April 2022. Reference Source\n\nHarris CE, Chestnutt IG: The use of the Internet to access oral health-related information by patients attending dental hygiene clinics. Int. J. Dent. Hyg. 2005 May; 3(2): 70–73. PubMed Abstract | Publisher Full Text\n\nPatton LL, George SF, Hollowell RP Jr: Content, quality, and readability of website information on dental care for patients with cancer. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2014 Jul; 118(1): 78–83. PubMed Abstract | Publisher Full Text\n\nFlesch R: A new readability yardstick. J. Appl. Psychol. 1948; 32: 221–233. PubMed Abstract | Publisher Full Text\n\nSilberg WM, Lundberg GD, Musacchio RA: Assessing, controlling, and assuring the quality of medical information on the Internet. JAMA. 1997; 277: 1244–1245. Publisher Full Text\n\nHealth on the net foundation. Chêne-Bourg – Switzerland: Health on the net foundation; 2015. Accessed on 2022 April 26. Reference Source\n\nBoyer C, Baujard V, Geissbuhler A: Evolution of healthweb certification through the HONcode experience. Stud. Health Technol. Inform. 2011; 169: 53–57. PubMed Abstract\n\nSilberg WM, Lundberg GD, Musacchio RA: Assessing, controlling, and assuring the quality of medical information on the Internet: Caveant lector et viewor--Let the reader and viewer beware. JAMA. 1997; 277(15): 1244–1245. Publisher Full Text\n\nCharnock D: Discern Handbook. The DISCERN instrument. Oxon: Radcliffe Medical Press; 1998.\n\nlast accessed 09/04/2024. Reference Source\n\nWiriyakijja P, Fedele S, Porter S, et al.: Web-based information on the treatment of oral leukoplakia – quality and readability. J. Oral Pathol. Med. 2016; 45: 617–620. PubMed Abstract | Publisher Full Text\n\nDiniz-Freitas M, Insua A, Keat R, et al.: Web-Based Information on the Treatment of Tobacco Dependence for Oral Health Professionals: Analysis of English-Written Websites. J. Med. Internet Res. 2017; 19: e349. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJoury AU, Alshathri M, Alkhunaizi M, et al.: Internet Websites for Chest Pain Symptoms Demonstrate Highly Variable Content and Quality. Acad. Emerg. Med. 2016; 23: 1146–1152. PubMed Abstract | Publisher Full Text\n\nNi Riordain R, McCreary C: Head and neck cancer information on the internet: Type, accuracy and content. Oral Oncol. 2009; 45: 675–677. PubMed Abstract | Publisher Full Text\n\nMcMorrow SM, Millett DT: Adult orthodontics: a quality assessment of Internet information. J. Orthod. 2016; 43: 186–192. PubMed Abstract | Publisher Full Text\n\nKummervold PE, Chronaki CE, Lausen B, et al.: eHealth trends in Europe 2005-2007: A population-based survey. J. Med. Internet Res. 2008; 10: 1–16.\n\nVivien A, Kowalski V, Chatellier A, et al.: Information quality in general public French-speaking websites dedicated to oral cancer detection. J. Stomatol. Oral Maxillofac. Surg. 2017; 118: 20–28.\n\nLin HY, Chen SC, Peng HLCM: Unmet information needs and clinical characteristics in patients with precancerous oral lesions. Eur. J. Cancer Care. 2015; 24: 911–919. PubMed Abstract | Publisher Full Text\n\nVarela-Centelles P, Insua A, Seoane-Romero JM, et al.: Available web-based teaching resources for health care professionals on screening for oral cancer. Med. Oral Patol. Oral Cir. Bucal. 2015; 20: e144–e149. PubMed Abstract | Publisher Full Text\n\nKiley R: Quality of medical informationon the internet. J. R. Soc. Med. 1998; 91: 369–370. PubMed Abstract | Publisher Full Text\n\nRogers SN, Hogg ES, Cheung WKA, et al.: The use of health related quality of life data to produce information sheets for patients with head and neck cancer. Ann. R. Coll. Surg. Engl. 2015; 97: 359–363. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPai M, Avinash BR, Rajesh G, et al.: Analysis of internet Educational websites on tobacco cessation. [Dataset]. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "306334",
"date": "16 Aug 2024",
"name": "Venkitachalam Ramanarayanan",
"expertise": [
"Reviewer Expertise Dental Public Health. Evidence synthesis",
"Dental Education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction Effective tobacco cessation techniques and sources: Kindly use a different terminology for sources.\n\nSome information on the prevalence or burden of tobacco use especially among adolescents or adults could add more context to the introduction.\n\nVarious web resources - could add a few examples here.\n\nMethods There is no mention of study design. I feel it can be closely related to, though purely not, a \"Health Technology Assessment\"\nGoogle, a common search site, was deployed to search for content on tobacco cessation - What were the search words used in Google. It is very important to mention this as it determined the \"hits\" obtained. Was the wording used in tune with what a layman would use? How did the team come to a consensus on which words to use?\n\nThe manuscript could explain a bit more on the different scales used to assess the quality and readability ... Why were these scales chosen and what aspect it measures? .. Even though citations have been provided, it would be beneficial for the reader if a brief idea is given about these scales.\n\nThe parameters were entered - Parameters would be more clear if the above comment is incorporated.\n\nHow many investigators evaluated the websites? As some of the parameters seem subjective, How was reliability ensured?\nWould be interesting and informative to note how readability score levels were assessed.\n\nThe findings of the current study indicate that a total of 10 (23%) of the websites satisfied all 4 JAMA benchmarks. Overall, the number of websites satisfying 1, 2 and 3 of the JAMA benchmarks was 6 (14%), 7 (16%) and 19 (44%), respectively. - 1, 2 and 3 of JAMA benchmarks need to be named. There is no table for this which would help the uninitiated reader to understand the tool.\n\nThe median and mean scores for questions in DISCERN-16. It can be observed that the mean score was maximum for item number 1 and was minimum of 2.91 for item numbers 5, 6 and 8. A majority of 21 (49%) of the websites as assessed by DISCERN-16 belonged to the fair category, while none of the websites belonged to the very poor and excellent categories. - Need a table for this. Item numbers 5,6 and 8 needs to be elaborated.\n\nDiscussion\nAdd more information on HONcode certification. How will a layman be able to identify it ?\nThe assessment of the content of the websites was performed by using a checklist prepared specifically for the present study. - Provide checklist as an attachment\n\nWould have been more interesting to explain more on the websites which were selected. Was it government websites? professional bodies? or blogs etc, ... who were the authors .. what was the content .. all of this in brief at least ..\n\nWhat guidance do you offer to a layman to ensure that the website he reads is of good quality. Any red-flags you can propose based on your analysis?\nConclusion\nwere not up to the mark.- Reframe using scienfic language\nOverall comments\n- The study is interesting and relevant. But the information provided is too short, superficial and generic. There is scope for explanation in all sections of the manuscript which would help the reader follow the article better. The quantum of work done in evaluating all 41 websites using various scales is not reflecting in the manuscript.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "312908",
"date": "26 Aug 2024",
"name": "Tarakant Bhagat",
"expertise": [
"Reviewer Expertise Dental public health",
"epidemiology",
"oral health",
"health literacy"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract and Introduction Whenever using an abbreviation, please mention it along with the full form for the first time; e.g: Flesch–Kincaid (FK), JAMA, HONcode, DISCERN etc. Methods i. Who all were involved in the screening process? Incase multiple person were involved, how was the dispute resolved, if there was any? ii. Various tools were used, please mention how the scores of each tool was calculated. Also, mention the number of questions used in each tool; e.g. DISCERN-16. Results i. What does \"satisfied all 4 JAMA benchmarks\" indicate? ii. Please make the short-terms uniform. e.g: HONcode v HONCODE. iii. Table 2: Is it necessary to mention 1% significance level when in the methods section it is mentioned as 5%? Will it make any difference? Discussions i. \"Moreover, health literacy levels, and access to the internet may vary among patients\" - Please provide references. ii. \"Further studies that consider a greater number of websites need to be conducted\" - What is the minimum or maximum number of websites required for content analysis? Conclusions \"It can be observed that the read-ability ease and read-ability grade levels of the websites related to tobacco cessation were not up to the mark\" - but the results showed that 49% were standard content. Please justify.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-822
|
https://f1000research.com/articles/13-246/v1
|
04 Apr 24
|
{
"type": "Research Article",
"title": "Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations",
"authors": [
"Haruna Luz Barazorda-Ccahuana",
"Eymi Gladys Cárcamo Rodriguez",
"Angela Emperatriz Centeno-Lopez",
"Margot Paco-Chipana",
"Luis Daniel Goyzueta-Mamani",
"Miguel Angel Chavez-Fumagalli",
"Haruna Luz Barazorda-Ccahuana",
"Eymi Gladys Cárcamo Rodriguez",
"Angela Emperatriz Centeno-Lopez",
"Margot Paco-Chipana",
"Luis Daniel Goyzueta-Mamani"
],
"abstract": "Background The coronavirus disease (COVID-19) pandemic continues to be a public health problem worldwide. Several therapeutic targets of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, whereas the main protease (Mpro) is necessary for virus replication. Since SARS- CoV-2 Mpro mutation rates are inherently high, searching for new inhibitors remains challenging. Herein, this work aimed to evaluate 84 natural compounds from Peruvian sources against different mutations on the Mpro target.\n\nMethods We applied virtual screening, all-atom molecular dynamics simulations, and binding free energy estimation by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA).\n\nResults The virtual screening results helped us identify rutin as the top compound against different Mpro mutations. Likewise, the computational simulations demonstrated the high structural stability of the Mpro-rutin system.\n\nConclusions his research evaluated the antiviral capacity of Peruvian sources against SARS-CoV-2 Mpro and its mutations, which could be important in preventing and treating SARS-CoV-2 infection.",
"keywords": [
"Main protease",
"mutations",
"SARS-CoV-2",
"Peruvian sources",
"rutin"
],
"content": "Introduction\n\nAt the end of 2019, the world observed the outbreak of the coronavirus disease (COVID-19) pandemic, which began to spread within communities and hospitals, causing numerous persons to become infected.1 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for triggering the pandemic known as COVID-192,3 and until today, the virus transmission is wreaking on public health4 and the world economy.5 Several countries had reported variants of SARS-CoV-2, and by the end of the second half of 2020, they had rapidly spread.6,7\n\nThe SARS-CoV-2 main protease (Mpro) is a key enzyme that plays a fundamental role in mediating viral replication and transcription.8 Mpro processes the polyprotein 1ab at multiple cleavage sites and hydrolyses the Gln-Ser peptide bond in the Leu-Gln-Ser-Ala-Gly recognition sequence. This cleavage site in the substrate is distinct from the peptide sequence recognized by other human cysteine proteases known to date.9 It is also considered a potential therapeutic target since its inhibition could help block the virus’s translation and replication.10 Mpro comprises three domains: domains I, II, and III, composed of 8-101, 102-184, and 201-306 amino acid residues, respectively.8\n\nLikewise, several researchers had highlighted the importance of studying the stability of Mpro structure taking to account the mutations, since it would be challenging to identify specific inhibitors.11 These variants are characterized by changes in the amino acid sequence of the virus when compared with the first sequenced strain Wuhan-Hu-1 (Gen- Bank accession: NC_ 045512.2); the variants may have one or more mutations that differentiate them from the wild type.12 The SARS-CoV-2 genetic variations are crucial to track and evaluate their spread in countries. It must be considered that the registered mutations can change the binding mechanisms of possible inhibitors developing a potential resistance.13 Therefore, it is crucial to anticipate the effect and identify new inhibitors that counteract these effects. In the absence of a specific drug and the appearance of new mutations, different studies evaluate the potency of many phytochemicals to restrict the multiplication of SARS-CoV-2 and other viral infections.14 Phytocompounds might be the most promising drug candidate in the current need since they have high bioavailability and low toxicity.15 Likewise, in silico studies have shown the potent inhibitory action against SAR-CoV-2 Mpro of taraxerol from Clerodendrum spp. used in traditional medicine in Asia tropical regions16 and the β-amyrin and stigmasta-5,22-dien-3-ol present in Cyperus rotundus L. used in traditional medicine in India.17\n\nPeru is one of the 12 nations with the largest percentage of biodiversity, and because of this, a living legacy of traditional medicine has been able to grow and endure over time.18 The Vavilov Institute views this region as a global hub for floral biodiversity.19 The 20,000–30,000 plant species found in the various locations make up roughly 10% of all the plants used as medicine worldwide.20\n\nThis study used the Peruvian Natural Products Database (PeruNPDB) dataset for docking-based virtual screening. Subsequently, the best compound was analyzed by molecular dynamics simulations and binding free energy estimation from eight SARS-CoV-2 Mpro mutated (Y54C,21 N142S,21 T190I,21 A191V,21 S139A,22 R298A,22 R60C,13 and G11A23).\n\n\nMethods\n\nThe SARS-CoV-2 Mpro crystal structure was selected. To sample the mutations, they were obtained of the native sequence only for the Mpro reported in the Protein Data Bank by the access code PDB ID: 5RE4, which each amino acid was replaced for eight mutations in search of new challenges (R298A, N142S, A191V, R60C, G11A, Y54C, T190I, and S139A). The preparation of mutated systems was done by homology modeling in the SWISS-MODEL server using the crystal structure of SARS-CoV-2 Mpro (PDB ID: 5RE4) as a template.\n\nThe search for natural products was performed at the Peruvian Natural Products Database (PeruNPDB) online web server (first version) (accessed on 23 January 2022),24 whereas the simplified molecular-input line-entry system (SMILE) of each compound of was the upload into OpenBabel within the Python Prescription Virtual Screening Tool (PyRx)25; and the subjection to energy minimization; whereas PyRx performs structure-based virtual screening by applying docking simulations using the AutoDock Vina tool.26 Likewise, the FASTA sequence of the Crystal Structure of SARS-CoV-2 main protease (Mpro) (PDB: 5RE4) was subjected to a BLAST search (accessed on 16 April 2022),27 whereas all the mutants were selected and subjected to automated modeling in SWISS-MODEL server (accessed on 17 April 2022).28 For the analysis, the search space encompassed the whole of the modeled 3D models; and the docking simulation was then run at exhaustiveness of eight and set to only output the lowest energy pose. Multiple sequence alignments of the Mpro and mutant sequences were visualized using the msa package (version 1.22.0)29 in the R programming environment (version 4.0.3). The heatmap plot was generated using GraphPad Prism version 9.4.0 (673) for Windows, GraphPad Software, San Diego, California USA.\n\nThe simulation of the motion is realized by the numerical solution of the classical Newtonian dynamic equations.30 We used Gromacs v. 2020 to calculate the molecular dynamics (MD) simulation and the AMBER-99SB-ILDN force field. The topologies for the Amber force field were determined on the ACPYPE server for the best metabolite against mutates Mpro. Each system was included in the center of a cube box of 10 on each side. Likewise, water molecules were added (water model TIP4P). The energy minimization was carried out with the steep-descendent integrator with 200,000 calculation steps. Herein, the MD simulation in the canonical ensemble NVT was done for a time of 1 ns. Finally, the production of MD continued 100 ns in the isobaric-isothermal ensemble considering the Parrinello-Rahman barostat (1 bar) and V-rescale thermostat (309.65 K). The binding free energy estimation by MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) was calculated with the suit mmpbsa.py31 from AmberTools2032 and gmx MMPBSA v1.4.1.33 The equations related to calculations of binding free energies are the following:\n\nThe equation that determines the electrostatic solvation energy (∆GGB) considers (∆EM M) which is the variation between the minimized energy of the protein-ligand complexes of the study which includes the van der Waals (∆Evdw) and electrostatic (∆Eele) contributions, while (∆GSA) is the difference in surface area energies for protein and ligand and (T∆S) refers to the contribution of entropy at temperature T.\n\nFinally, the graphical visualizations were made with Visual Molecular Dynamics (VMD),34 allowing interactive visualization with an easy-to-use interface. The interpretation of the molecular interactions was recreated with Maestro (Schrodinger) 2D interactions diagram. Likewise, the Molecular dynamics simulation results were performed by the Gromacs tools, and the values were processed by Gnuplot 5.2 command-driven interactive function plotting program.\n\n\nResults\n\nSARS-CoV-2 Mpro is a cysteine protease of 67.6 kDa, and its structure possesses a catalytic dyad (Cys145 and His41) with a substrate-binding pocket located in a cleft between domains I and II. The secondary structure of Mpro has 10 alpha helixes, 13 beta sheets, and eight beta protrusions, seven beta hairpins, 22 beta turns, five gamma turns, and nine helix-helix interactions. In this work we used the access code PDB ID: 5RE4, which was downloaded from the Protein Data Bank. This crystal structure was determined by the X-ray diffraction method with a resolution of 1.88 Å.\n\nWe also focused on the analysis of eight mutations registered in different parts of the world. First is the Y54C mutation reported in Malaysia, and the N142S mutation was reported 17 times in five different countries. T190I is a mutation identified in 15 countries, such as South Africa and the USA. The mutation A191V is characterized by having an occurrence rate of 0.30% and is present in more than 34 countries. Besides, in the S139A, G11A, and R298A,35 mutations result in the complete loss of dimerization.36 In Brazil and Vietnam, the R60C mutation was reported, affecting the protein dynamics and the inhibitor’s binding within its active site.13 The R298A leads to the interruption of the dimeric conformation and irreversible inhibition of the enzyme’s catalytic activity,36 and the G11A mutation avoids the insertion of the N finger region (residues 1-9) and therefore wholly declines its activity.37 The location of the eight mutations is shown in Figure 1.45\n\nThe beads represent the location of each mutation on both Mpro chains. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Mpro, main protease.\n\nFigure 2 shows the sequence alignment of Mpro mutations. The black square selects the variation of residues by mutant Mpro. The G11A, Y54C, and R60C mutations are located close to the His41 residue and in Domain I from Mpro. Two mutations (S139A and N142S) are present in the Domain II and close to the Cys145, and it is expected that these protein structures could show different behavior than Mpro without mutations. On the other hand, it was also observed that mutations in T190I and A191V are in the connection of Domain II and Domain III. For the case of R298A mutation, it can be observed near Domain III.\n\nThe blue, red, and purple boxes represent Domain I, Domain II, and Domain III, respectively. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Mpro, main protease.\n\nThe virtual screening technique, widely used for drug discovery, seeks to identify potential compounds for a particular therapeutic target. This approach allowed us to find new possible candidates within the PeruNPDB dataset against one of the therapeutic targets from mutant Mpro of SARS-CoV-2.\n\nThe 84 substances included in the study are taken from the original PeruNPDB collection; the most recent dataset consists of 280 substances. Figure 3 shows the gradient palette, the violet color indicated strong binding (∆G<-12 kcal/mol), while the yellow color indicated weak binding (∆G>-2 kcal/mol). In this heat map, rutin is shown the best compounds. However, for the T190I and Y54C mutations, the color intensity is lower compared to the other mutations.\n\nSARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Mpro, main protease.\n\nIn Table S1 of the underlying data,45 the values of coupling energies are reported. The values for Mpro wild, A191V, G11A, N142S, R60C, R289C, S139A, T190I, and Y54C were -10.7 kcal/mol, -10.4 kcal/mol, -10.7 kcal/mol, -10.4 kcal/mol, - 10.7 kcal/mol, -10.7 kcal/mol, -10.7 kcal/mol, -9.4 kcal/mol, and -9.1 kcal/mol, respectively.\n\nThe results obtained from virtual screening helped us to consider rutin as a ligand against the different Mpro mutations. Molecular dynamics simulations allow us to understand the behavior of different mutated Mpro at an atomistic level. After analyzing 100 ns of production dynamics, the convergence of each protein is observed by Root-mean squared deviation (RMSD) analysis (see Figure 2A). This result shows us that the different types of mutations achieved equilibrium; likewise, an average RMSD between 0.1 and 0.2 nm is appreciated, an acceptable value in this structural model. The Root-mean squared fluctuation (RMSF) calculates the flexibility of individual residues that make up the Mpro protein during a simulation trajectory. The RMSF per residue diagram structurally indicates which amino acids in a protein contribute the most to a molecular motion. Figure 4B highlights the area of His41 and Cys145 amino acids where the most significant fluctuation in the His41 area occurs with the R298A mutation, while the most significant fluctuation in the Cys145 area occurred in the R60C, Y54C, R298A, and N142S mutation.\n\nA.) RMSD of eight SARS-CoV-2 Mpro with rutin. B.) RMSF of the last 5 ns per residue of each SARS-CoV-2 Mpro mutated, highlighting the principal residues of the catalytic dyad (His41 and Cys145). RMSD, Root-mean square deviation; RMSF, Root-mean square fluctuation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Mpro, main protease.\n\nOn the other hand, Table 1 shows us the quantitative values of the RMSD, where the G11A and R60C mutations showed the lowest average RMSD value. By contrast, the average value for the Y54C mutation was higher than the others. Regarding the average RMSF values of the last 5 ns, for the 5RE4, A191V, G11A, N142S, R60C, S139A, and T190I systems, the average RMSF of the Mpro structures oscillated by 0.8 nm, while for R298A the RMSF average results in 0.09 nm and Y54C it was 0.07 nm.\n\nThe results of the binding free energy estimation were performed by the MM/GBSA method with all frames of the MD. Table 2 indicates the average free energy values for each system. The values show a high coupling energy estimate, indicating that the interaction was carried out correctly.\n\nThe mutation R60C showed the best interaction energy (-45.09 kcal/mol) against the different systems studied. The energy values for G11A and A191V were -41.17 kcal/mol and -40.71 kcal/mol, respectively. While the systems that showed low binding energy were mutations R298A and S139A, with average values of -24.11 kcal/mol and -25.84 kcal/mol, respectively.\n\nLikewise, the most significant energy contribution was given by the Van der Waals energies (VDWAALS) in the wild systems, A191V, G11A, N142S, R298A, S139A, and T190I. These types of energy are weak and are short-range interactions; in biological systems, they play a significant role in stabilizing protein-small molecules. On the other hand, in the R60C and Y54C systems, the energy contribution is given by electrostatic energies (EEL). Electrostatic energy takes into account the charges of each atom in the system, which depend on the medium in which they are found; these have greater scope, and the force of interaction it possesses is linked to the relative orientations it accepts.\n\nFigure 5 shows the last frame of each simulation of the Mpro-rutin complex. In general, it was observed that the interactions in the active site are due to the formation of hydrogen bonds. However, we observed some changes in the region around the active site for the mutations occurring in N142S and Y54C. The residues around N142S are mostly hydrophobic (green contour), hence N142S exhibits a greater energy contribution from hydrophobic interactions (VDWAALS = -54.18 kcal/mol, higher than the other mutations). While in Y54C, the residues around rutin are polar (sky blue contour), demonstrating its high energetic contribution by electrostatic interactions (EEL = -66.78 kcal/mol more elevated than the other mutations).\n\nThe pink arrow lines represent the hydrogen bond. Mpro, main protease.\n\n\nDiscussion\n\nUntil today, different research teams worldwide have collected information on SARS-CoV-2 strains since some show many mutations in the different structural proteins, like the main protease. Mutations affect the stability of the 306 residues of the main protease, giving them new characteristics.38 Regarding other in silico studies carried out in sequences of SARS-CoV-2 Mpro mutated from India and Vietnam, they showed that this change in the genome affected the stability of the protein and impacted the catalytic zone.13 For this reason, it is crucial to investigate how these mutations in SARS-CoV-2 Mpro can be inhibited and could prevent SAR-CoV-2 replication.\n\nDifferent phytochemical molecules such as kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin gallate have been reported with promising antiviral drug against SARS-CoV-2.39 Also, Parvez et al., reported azobechalcone, rifampin, isolophirachalcone, tetrandrine, and fangchinoline as potential inhibitors of SARS-CoV-2 Mpro,40 and Padhi et al., who obtained that putaminoxin B, putaminoxin D, jasmonic acid, and jasmonic methyl ester with good pharmacokinetic properties against Mpro.41 In 2020, more than a thousand FDA-approved drugs were virtually screened using molecular docking and binding free energy calculations, where nelfinavir was suggested as a potential inhibitor against SARS-CoV-2.\n\nGoyzueta et al., studied rutin compound as a promising inhibitor against the native SARS-CoV-2 Mpro by in silico techniques.42 Likewise, reused drugs and phytochemical compounds showed a binding affinity against some Mpro mutants; for example, salvianolic acid A (extracted from S. miltiorrhiza) shows an inhibition effect against N142S and T190I.21 The novelty of this work was to use a database of compounds designed with metabolites from Peruvian plants reported in the literature. Our results demonstrate that the rutin metabolite present in S. sonchilofolius (commonly known as yacón) and L. meyenii (commonly known as maca andina) had the best binding affinity with all proposed Mpro mutations. Rutin is known as rutoside and it is a natural phenolic compound with an essential role in the oxidant- antioxidant balance associated with some diseases.43,44\n\nMolecular dynamics simulation provides us with information on the structural stability of the protein at a given time by RMSD and RMSF analysis. Here the RMSD results were within an acceptable average in all systems, which indicates that the rutin molecule forms a highly stable complex. Additionally, the binding energy was also evaluated with the help of the MM/GBSA approach. In these, we have observed that the mutations located close to the active center are the ones that achieved the best energy contributions. In general, it was observed that all the Mpro-rutin systems have a high affinity.\n\n\nConclusions\n\nSARS-CoV-2 mutations have caused worry because some mutations can make the virus more aggressive and spread faster. Currently, several mutations have been reported in different therapeutic targets of SARS-CoV-2. The main protease (Mpro) is essential for SARS-CoV-2 replication and is a promising drug target. Here, we have focused on eight mutations of the SARS-CoV-2 Mpro (Y54C, N142S, T190I, A191V, S139A, R298A, R60C, and G11A) and analyzed several compounds from Peruvian natural sources by virtual screening methods, where rutin was the most suitable compound. Molecular dynamics simulations and binding free energy estimation by MM/GBSA showed high stability of the Mpro- rutin complex and excellent energetic affinity, respectively. These results demonstrated the database PeruNPDB’s utility in finding rutin as a promising inhibitor of different SARS-CoV-2 Mpro mutations.\n\n\nEthics and consent\n\nEthical approval and consent were not required.\n\n\nAuthor contributions\n\nConceptualization: H.L.B.-C. and L.D.G.-M.; data curation: H.L.B.-C., L.D.G.-M., E.G.C.-R., A.E.C.-L., M.P.-C., and M.A.C.-F; formal analysis: H.L.B.-C. and M.A.C.-F.; funding acquisition: H.L.B.-C. and M.A.C.-F.; investigation: H.L.B.-C., M.P.-C., L.D.G.-M., E.G.C.-R., A.E.C.-L., and M.A.C.-F; methodology: H.L.B.-C. and M.A.C.-F.; writing—review and editing: H.L.B.-C., and M.A.C.-F. All authors have read and agreed to the published version of the manuscript.",
"appendix": "Data availability\n\nFigshare: Dataset of results from virtual screening and molecular dynamics simulations. https://doi.org/10.6084/m9.figshare.24271972. 45\n\nThis project contains the following underlying data:\n\n1. Table S1. (Virtual screening results of the compounds selected against SARS-COV2 Mprotein mutations).\n\n2. Table S2. (Molecular dynamics simulations results of the compounds selected against SARS-COV2 Mprotein mutations).\n\n3. Table S3. (Molecular dynamics simulations results of the compounds selected against SARS-COV2 Mprotein mutations).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nXiang Y, Li N: Understanding the beginning of a pandemic: China’s response to the emergence of covid-19. J. Infect. Public Health. 2021; 14(3): 347–352.\n\nBen H, Guo H, Zhou P, et al.: Characteristics of SARS-CoV-2 and covid-19. Nat. Rev. Microbiol. 2021; 19(3): 141–154. 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}
|
[
{
"id": "269268",
"date": "17 May 2024",
"name": "Tushar Joshi",
"expertise": [
"Reviewer Expertise Antibacterial and Antiviral Resistance"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nEditorial note from F1000Research: This report was originally published on 17th May 2024 with an approval status of 'Approved', but the reviewer has now clarified that their approval status was intended to be 'Approved with reservations', so on 27th May 2024 the approval status of the report has been updated accordingly to reflect this.\nThe research article entitled “Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations” has found rutin is a potential inhibitor against SARS-CoV-2 Mpro mutations. The research topic is interesting. There are recommendations for the authors to make the manuscript more effective for readers. The manuscript can be considered for indexing on addressing the following major comments.\nThe abstract conclusion is not that effective, it could be more effective. It should not start with “his”, kindly rephrase it.\n\nThe abstract is not very effective, kindly re-write it. Kindly refer to these research papers for better understanding: Mathpal et al. (2022(1) and Joshi et al. (20222) and cite them accordingly.\n\nThe authors have not analyzed the properties of mutations either these are deleterious in nature or neutral mutation. There are many online servers like Meta-SNP. Authors can use these servers.\n\nThe authors have not analyzed the ADMET and Lipinski properties of compounds. Kindly include these methods.\n\nIn the results, the authors have written that mutation is collected from different sources. The short part should be written on the material method and a long can be written on the discussion part.\n\nThe results of RMSD are good but for better understanding kindly analyze interaction energy.\n\nThe authors have been unable to explain how this study is different from other studies that have also found rutin against Mpro.\n\nThere are many loopholes in this study.\n\nThe discussion and conclusion are also not written perfectly. Kindly try to cite recent publications.\n\nThere is a high recommendation for authors to use professional software or language experts to correct the grammar and language of the manuscript. There are many places where sentences look incomplete and create confusion for readers.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12558",
"date": "29 Oct 2024",
"name": "Miguel Angel Chavez-Fumagalli",
"role": "Author Response",
"response": "The research article entitled “Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations” has found rutin is a potential inhibitor against SARS-CoV-2 Mpro mutations. The research topic is interesting. There are recommendations for the authors to make the manuscript more effective for readers. The manuscript can be considered for indexing on addressing the following major comments. The abstract conclusion is not that effective it could be more effective. It should not start with “his” Kindly rephrase it. Answer: The abstract was improved The abstract is not very effective kindly re-write it. Kindly refer to these research papers for better understanding Mathpal S, et.al., 2022 (Ref 1) and Joshi T, et.al., 2022 (Ref 2) and cite them accordingly. Answer: The abstract was improved The authors have not analyzed the properties of mutations either these are deleterious in nature or neutral mutation. There are many online servers like Meta-SNP. Authors can use these servers. Answer: A mutation analysis was done, this was incorporated on Page 4 The authors have not analyzed the ADMET and Lipinski properties of compounds. Kindly include these methods. Answer: Information was added on Page 5 and Page 6 from the “Virtual Screening analysis” subsection. In the results, the authors have written that mutation is collected from different sources. The short part should be written on the material method and a long can be written on the discussion part. Answer: Information was added on page 9. From the “Discussion” section. The results of RMSD are good but for better understanding kindly analyze interaction energy. Answer: Information was added on page 9. From the “Discussion” section. The authors have been unable to explain how this study is different from other studies that have also found rutin against Mpro. Answer: Information was added on page 9. From the “Discussion” section. There are many loopholes in this study. Answer: The manuscript was revised and improved The discussion and conclusion are also not written perfectly. Kindly try to cite recent publications. Answer: The manuscript was revised and improved There is a high recommendation for authors to use professional software or language experts to correct the grammar and language of the manuscript. There are many places where sentences look incomplete and create confusion for readers. Answer: The manuscript was revised and improved"
}
]
},
{
"id": "290175",
"date": "25 Jun 2024",
"name": "Mohammed Bouachrine",
"expertise": [
"Reviewer Expertise Drug Design",
"Molecular Modeling",
"in-silico studies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nToday, numerous studies are studying the different mutations of SARS-CoV-2 which are worrying and which can make the virus more aggressive and spread faster. Along these lines, the authors studied eight SARS-CoV-2 Mpro mutations (Y54C, N142S, T190I, A191V, S139A, R298A, R60C, and G11A) and analyzed several compounds from Peruvian natural sources by virtual screening methods. Molecular dynamics simulations and binding free energy estimation by MM/GBSA showed high stability of the Mpro-rutin complex and excellent energy affinity, respectively. These results demonstrated the database the utility of PeruNPDB in finding rutin as a promising inhibitor of different SARS-CoV-2 Mpro mutations. The results are numerous and interesting, the article corresponds perfectly to the objectives of the journal. I recommend its publication after a few corrections\n\nAuthors are invited to better rewrite the abstract and the conclusion The authors are invited to explain and to detail the mechanism of action The authors must justify the choice of the protein Why did the authors not pursue the studies using other in-silico techniques Authors must cite work published in this journal and other journals on the same studies\n\nActa Pharm. Sin. B (2020), 10.1016/j.apsb.2020.02.008 https://doi.org/10.1016/j.molstruc.2022.132652 https://doi.org/10.1080/07391102.2020.1758790 Life Sci., 251 (2020), Article 117627, 10.1016/j.lfs.2020.117627 https://doi.org/10.2174/1386207323999200730205447 https://doi.org/10.1038/nature17180, 2-s2.0-84982234143. https://doi.org/10.1080/07391102.2020.1779130 https://doi.org/10.1016/j.compbiomed.2021.104758 https://doi.org/10.1155/2021/1901484\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12559",
"date": "29 Oct 2024",
"name": "Miguel Angel Chavez-Fumagalli",
"role": "Author Response",
"response": "Today, numerous studies are studying the different mutations of SARS-CoV-2 which are worrying and which can make the virus more aggressive and spread faster. Along these lines, the authors studied eight SARS-CoV-2 Mpro mutations (Y54C, N142S, T190I, A191V, S139A, R298A, R60C, and G11A) and analyzed several compounds from Peruvian natural sources by virtual screening methods. Molecular dynamics simulations and binding free energy estimation by MM/GBSA showed high stability of the Mpro-rutin complex and excellent energy affinity, respectively. These results demonstrated the database the utility of PeruNPDB in finding rutin as a promising inhibitor of different SARS-CoV-2 Mpro mutations. The results are numerous and interesting, the article corresponds perfectly to the objectives of the journal. I recommend its publication after a few corrections Authors are invited to better rewrite the abstract and the conclusion Answer: The abstract and conclusions were improved The authors are invited to explain and to detail the mechanism of action Answer: The mechanism of action of Mpro in SARS-CoV-2 is explained in the “Introduction” section. The authors must justify the choice of the protein Answer: It was better explained in the “Introduction” section Why did the authors not pursue the studies using other in-silico techniques Answer: Our expertise lies in the employment of in-silico methodologies that are both reliable and widely recognized within the scientific community for the investigation of viral proteins. The decision to abstain from utilizing additional in-silico techniques was based on practical and strategic considerations. Initially, the techniques implemented in this study, including virtual screening, molecular dynamics simulations, and binding free energy estimation using the Molecular Mechanics/Generalized Born Surface (MM/GBSA) method, have already demonstrated exceptional effectiveness and dependability in the structural and functional analysis of viral proteins. These techniques provided an in-depth understanding of the molecular interactions between Mpro and the chosen natural compounds. It should be noted that the inclusion of more in-silico techniques could have increased the complexity and duration of the study without guaranteeing a proportional improvement in the quality of the results. It is important to emphasize that virtual screening was utilized to efficiently identify potentially effective compounds from a vast library of molecules, while molecular dynamics simulations were essential to examine atomic-level interactions between inhibitors and Mpro in a dynamic environment. These simulations provided detailed information on the structural stability of the complexes formed and the possible conformations adopted during the interaction. The MM/GBSA method allowed for the quantification of the affinity of the inhibitors for Mpro. Our primary objective was to provide precise and reproducible data within a reasonable time frame. By concentrating on well-established methodologies, we ensure the consistency and validity of our results, avoiding potential complications and variations associated with the use of lesser-known or invalidated techniques in the context of this specific study. Authors must cite work published in this journal and other journals on the same studies: Acta Pharm. Sin. B (2020), 10.1016/j.apsb.2020.02.008 https://doi.org/10.1016/j.molstruc.2022.132652 https://doi.org/10.1080/07391102.2020.1758790 10.1016/j.lfs.2020.117627 https://doi.org/10.2174/1386207323999200730205447 https://doi.org/10.1038/nature17180, 2-s2.0-84982234143. https://doi.org/10.1080/07391102.2020.1779130 https://doi.org/10.1016/j.compbiomed.2021.104758 https://doi.org/10.1155/2021/1901484 Answer: Citations have been incorporated"
}
]
}
] | 1
|
https://f1000research.com/articles/13-246
|
https://f1000research.com/articles/13-1404/v1
|
21 Nov 24
|
{
"type": "Research Article",
"title": "Exploring the experiences of the hemodialysis patients during the COVID-19 pandemic: A qualitative study",
"authors": [
"Dewiyanti Toding",
"Masfuri Masfuri",
"Agung Waluyo",
"Sri Yona",
"Reflin Mahmud",
"Sri Nining",
"Effita Piscesiana",
"Wasal Desrial Siregar",
"Rico Maulana Nugroho",
"Ropika Ningsih",
"Ida Ayu Md Vera Susiladewi",
"Masfuri Masfuri",
"Agung Waluyo",
"Sri Yona",
"Reflin Mahmud",
"Sri Nining",
"Effita Piscesiana",
"Wasal Desrial Siregar",
"Rico Maulana Nugroho",
"Ropika Ningsih",
"Ida Ayu Md Vera Susiladewi"
],
"abstract": "Background The impact and changes due to the COVID-19 pandemic on end-stage renal disease patients undergoing hemodialysis affect the patient’s fulfilment and quality of life.\n\nObjective This study aims to thoroughly investigate the experiences of end-stage renal disease patients undergoing hemodialysis during the COVID-19 pandemic.\n\nMethods This research uses a qualitative descriptive approach with in-depth interview methods. Participants numbered 15 people from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital, which were selected using a purposive sampling technique.\n\nResult There are three themes produced in this research: 1) various responses to the COVID-19 pandemic, 2) various impacts, and 3) coping mechanisms developed.\n\nConclusion These findings indicate that patients with end-stage renal disease who undergo hemodialysis have attempted to build adaptive coping strategies in this era of the COVID-19 pandemic. However, they still need support from healthcare providers in the hemodialysis unit to overcome various problems and impacts resulting from the COVID-19 pandemic. Hemodialysis nurses are expected to be able to carry out holistic assessments and continuous evaluation in order to provide comprehensive nursing care to meet patient needs for hemodialysis in the era of the COVID-19 pandemic.",
"keywords": [
"COVID-19",
"end-stage renal disease",
"hemodialysis",
"pandemic",
"patient experience",
"nurse",
"qualitative descriptive"
],
"content": "Introduction\n\nPatients with end-stage renal disease must undergo renal replacement therapy to continue life, and hemodialysis is one of the most common renal replacement therapies carried out throughout the world, including in Indonesia (Liew, 2018). End-stage renal disease patients are classified as a high-risk group for being infected with COVID-19 because they have several risk factors, such as advanced age, decreased immune status, diabetes, heart disease, and hypertension (Onder et al., 2020; Xiong et al., 2020; Valeri et al., 2020). Hemodialysis therapy is generally carried out in central hemodialysis units where patients, nurses, doctors and support staff can be present simultaneously during the hemodialysis process, so it is sometimes difficult to maintain social distance and restrictions (Rombolà & Brunini, 2020). Therefore, hemodialysis units have a high risk of COVID-19 transmission, including staff, fellow patients and the patient’s family (La Milia et al., 2020; Su et al., 2020). Li et al. (2020) said that fear and anxiety about being exposed to COVID-19 are also a severe challenge that hemodialysis patients must face. As a risk group, hemodialysis patients have a fear of not being able to face COVID-19 if they are exposed. As a high-risk group, hemodialysis patients fear they may not be able to cope with COVID-19 if exposed (WHO, 2020a). This concern is heightened by the limited availability of personal protective equipment in hospitals or for personal use, which can further increase their levels of anxiety and fear. Hemodialysis patients can experience changes in behaviour towards medication adherence during the COVID-19 pandemic (Sousa et al., 2020).\n\nHemodialysis patients should also take extra precautions to minimize the risk of exposure to the COVID-19 virus (Henry & Lippi, 2020). Hemodialysis patients must go to the unit hemodialysis 2-3 times per week and undergo 4-5 hour hemodialysis process, further increasing the patient’s risk of being exposed to COVID-19 (Su et al., 2020). Transportation to the hospital is also a challenge, as many hemodialysis patients have to face patients who depend on public transportation (Verma et al., 2020). Meijers, Messa, and Ronco (2020) suggest that hemodialysis patients use private transportation to the hemodialysis unit to reduce the contact risk of exposure to COVID-19. The COVID-19 pandemic can affect end-stage renal disease patients undergoing the process of hemodialysis and its treatment therapy. What is the condition of hemodialysis patients in Indonesia? During the COVID-19 pandemic, not much has been studied, especially regarding patients experiencing hemodialysis during the COVID-19 pandemic. Understanding the hemodialysis process during the COVID-19 pandemic from the experience and perspective of hemodialysis patients will make it easier for nurses to understand the patients needs. Data and information about the experience of hemodialysis patients are essential for nurses when providing hemodialysis treatment during this COVID-19 pandemic, so the nursing care provided is more comprehensive.\n\n\nMethods\n\nThis research used qualitative descriptive design that describes the experiences of end-stage renal disease patients undergoing hemodialysis in Indonesia in the era of the COVID-19 pandemic. This method is commonly used in health research and exploring various phenomena related to patient experiences (Doyle, McCabe, Keogh, Brady, & McCann, 2020). A qualitative descriptive research design was selected based on the research objectives, which aim to describe the experiences of patients undergoing hemodialysis for end-stage renal disease during the COVID-19 pandemic in a direct, extensive, and information-rich manner. Each patient has a unique perspective on their hemodialysis experience during the pandemic. Therefore, the researchers aimsto capture these perspectives to develop more suitable nursing interventions for them.. Thus, a qualitative descriptive research design is well-suited for this study.\n\nThis research was conducted in February 22 to May 22 2021 at Hasanuddin University Hospital and Wahidin Sudirohusodo Hospital. Recruitment of participants in this research used the method of purposive sampling with inclusion criteria including (1) patients undergone hemodialysis for more than three months, (2) negative PCR swab test result (not confirmed COVID-19), (3) more than 18 years old, and (4) able to communicate in Bahasa. The exclusion criteria were hemodialysis patients with cognitive impairment. The determination of participants is based on data adequacy. Once data saturation is reached, whereby no new insights or information can be derived from the participants (Bradshaw et al., 2017; Vasileiou et al., 2018).\n\nData collection method with in-depth interviews was used in this research. The interviewer was the first author, a dialysis nurse with 10 years of experience. She holds certification in dialysis nursing competency, master of nursing degree, has completed qualitative research courses and proficient in data collection through interviews. She has also practised conducting interviews with hemodialysis patients, though not with the specific participant.\n\nThe interview results were documented using voice record by phone to record participants’ verbal responses. The interview was conducted in person at the hospital and over the phone from home, in accordance with the prior agreement made with each patient before the interview.\n\nQuestions were focused on exploring the experiences of patients undergoing hemodialysis during the COVID-19 pandemic, following prepared guidelines for in-depth interviews. We employed a guideline-based interview approach, conducting semi-structured interviews with open-ended questions. In order to assess the efficacy of the interviewer and the interview protocol, we conducted preliminary interviews with three patients who were not part of the study. The outcomes of these preliminary interviews were documented and reviewed with the supervisors. The research proceeded only after obtaining supervisor approval to continue the interviews. Each interview was conducted individually, lasting between 60-90 minutes, with participants given the flexibility to take breaks or reschedule follow-up interviews as needed. Participants were interviewed individually to provide them with greater freedom to express themselves. When conducting interviews, the researcher remained attentive to research ethical principles and implementing health protocols. The interview ended on condition when the interview contract time had expired, the purpose of the interview had been achieved and the participants answers had become repetitive. Data saturation was achieved with the 15th participant, as no new information emerged, and therefore, no additional participants were recruited. No interviews were repeated in this study.\n\nData analysis carried out in this research used inductive thematic analysis consisting of 6 stages, namely recognizing and transcribing data, coding data, compiling themes, reviewing themes that have been prepared, giving names and definitions to themes, and making reports on research results (Braun et al., 2019). Every interview session was recorded and transcribed, and we used field notes to record participants’ expressions during the interview. Transcribed data were returned to participants for confirmation and clarification before being processed further. Additionally, the researchers’ considerations were documented throughout the analysis process to ensure the accuracy and validity of the data interpretation. NVivo 12 Plus was utilized for the analysis (QSR International Pty Ltd. Nvivo, 2024). The findings were shared with participants for verification. Two experts oversaw the research, and its validity was assessed through a thesis examination involving two expert examiners and nursing master’s students as reviewers. This comprehensive process ensured the research’s quality and reliability.\n\n\nResult\n\nThe participants in this research were 15 people, consisting of 9 males and 6 females. No one asked for withdrawing. Participants in this study were aged 23-66 years and had varying education levels, namely elementary school, middle school, high school, diploma, and bachelor’s degree. Participants’ jobs varied from entrepreneurs, freelancers, teachers, farmers, private employees, and students, and 6 participants did not work. Participants in this study came from 3 large tribes in South Sulawesi, with 7 participants from the Bugis tribe, 6 participants from the Makassar tribe and 2 participants from the Toraja tribe. The participants had undergone hemodialysis therapy for a period of between 2-8 years, with the majority undergoing the therapy two times per week.\n\nParticipants have carried out swab examinations PCR 3-20 times. Researchers conducted face-to-face interviews three times and telephone due to the COVID-19 pandemic situation (can be seen in Table 1).\n\nThe experiences of end-stage renal disease patients undergoing hemodialysis in the era of the COVID-19 pandemic have yielded three overarching themes. These themes encompass the following: (1) the emergence of diverse responses at the onset of the pandemic, (2) the emergence of various impacts throughout the pandemic, and (3) the development of coping strategies during the pandemic.\n\nTheme 1: The emergence of diverse responses at the onset of the pandemic\n\nThe research team identified the initial theme through an analysis of participant responses regarding their experiences with hemodialysis during the early stages of the pandemic. The findings revealed a range of negative reactions, which were grouped under the sub-theme “emotional response and behaviour response.”\n\nEmotional response\n\nAt the outset of the pandemic, participants described a range of negative emotional responses. At the outset of the COVID-19 pandemic, individuals undergoing hemodialysis expressed concerns, apprehension, and distrust. Anxiety was reported by nearly all participants at the onset of the pandemic. The majority of participants expressed concern that they might encounter difficulties in accessing hemodialysis in the event of a positive test result for SARS-CoV-2. Additionally, the majority of participants expressed concern about developing symptoms similar to those observed in patients with COVID-19 at the onset of the pandemic. It is not uncommon for patients with chronic kidney failure undergoing hemodialysis to present with symptoms such as cough, shortness of breath, flu-like symptoms, and fever. Some participants indicated that they experienced feelings of anxiety in relation to both fellow hemodialysis patients and hemodialysis nurses. Such feelings of anxiety are a consequence of the suspicion that either the patient or the nurse may be carrying the SARS-CoV-2 virus.\n\n“This swab keeps making me scared because this also keeps my blood pressure rising” (P2).\n\n“I am afraid because it will be difficult for me later. Finding hemodialysis schedules and entering isolation are problematic. It is hard if we get COVID-19” (P3).\n\n“Had I been provided with the swab, I would have experienced a sense of unease and anxiety tend to ruminate on issues, which can precipitate a state of physical illness” (P4)\n\n“We have a disease and are prone to be affected. That is why there is a disease that we carry. We were nervous about receiving the swab results” (P5).\n\n“Frequently, I experienced feelings of anger and frustration. However, I refrained from expressing my emotions towards other patients. At most, I informed the nurse to request a swab test, as I was concerned about the potential risk of contracting a disease in this environment” (P13).\n\n“I feared that I would not be provided with a hemodialysis machine, given the limited availability of such devices for use in patients with COVID-19” (P14).\n\nFurthermore, some participants articulated apprehension regarding the potential for testing positive for COVID-19 infection due to their classification as a high-risk group. This concern arises because patients with chronic kidney disease have an immune system that is compromised, rendering them more susceptible to infection by COVID-19, as expressed by the participants:\n\n“We are at higher risk because we have a pre-existing condition. That is why we are anxious” (P5).\n\n“The result of the swab should not be positive because my fear is overwhelming. It is not just that we (hemodialysis patients) have kidney disease, but the doctors have said we are more susceptible, more at risk of contracting COVID-19” (P6).\n\n“What worries me is the isolation room because no visitors are allowed. I feel bad because I cannot walk or do anything on my own, so I am worried about how I will manage inside if no one can visit” (P9).\n\nBehavioural response\n\nIn the initial stages of the global pandemic caused by COVID-19, individuals exhibited a range of behavioural responses to concerns, fears, and suspicions. Such behaviours include maintaining compliance with hemodialysis, concealing one’s health status, and disregarding social etiquette. This is exemplified by patients with dependent terminal chronic renal failure who undergo hemodialysis therapy to maintain survival. From the outset of the pandemic, participants expressed concern and apprehension about COVID-19. Nevertheless, all participants endeavoured to persevere with their hemodialysis regimen.\n\n“I’m concerned because my throat is itchy and I’ve been told that coughing is a symptom of corona. If I can treat it myself, I’d prefer to do so and not have to tell anyone else” (P2)\n\n“what else can I do? This is my fate; I have to go to dialysis if I want to survive” (P15)\n\nParticipants chose to hide their own or their family’s health status due to fear of being stigmatized as having COVID-19 or being in contact with someone who had it. For example, one participant mentioned:\n\n“I hope it’s just a regular cough because of an itchy throat and not labelled as COVID-19. If it’s something we can treat, let’s not jump to conclusions” (P2)\n\n“I hid my husband from the nurse because I was afraid that my husband would be suspected, even though I was the one who was sick, my husband was not” (P3)\n\nAnother behavioural response observed was a disregard for social norms and etiquette. Some participants exhibited a tendency to disengage from social interactions because they were excessively afraid of contracting COVID-19.\n\n“Friends who were close now keep their distance, saying ’stay away.’ They weren’t snobbish before, but now they are. I would rather that than catch COVID-19” (P2).\n\n“I am careful about who comes into my house. I would rather offend someone than risk it. Neighbours who used to visit now stay away because I get angry at them. Let them be offended; I would rather be safe” (P3).\n\nTheme 2: Various impacts\n\nThe COVID-19 pandemic has had many impacts on various sectors of participants’ lives as patients with end-stage renal disease undergoing hemodialysis. These various impacts are summarized in the sub-themes of physical, psychological, social, and economic impacts and protocol implementation health experienced by participants during the COVID-19 pandemic.\n\nPhysical impact\n\nThe majority of participants reported experiencing physical effects, including weight gain during interdialytic periods, shortness of breath, elevated blood pressure, pain, discomfort, and bleeding. The most frequently reported issue was interdialytic weight gain. As a consequence of the pandemic, the patient’s hemodialysis schedule was postponed. It should be noted that swab results were not available. In addition, some patients’ schedules have been modified as a result of the hemodialysis unit’s efforts to optimize the hemodialysis schedule. Shortness of breath represents a physical impact experienced by participants as a consequence of delays or alterations to their hemodialysis schedules. An increase in blood pressure is also a physical impact experienced by hemodialysis patients during COVID-19 pandemic due to anxiety about swab results. Some participants exhibited considerable anxiety regarding the results. The swab yielded a positive result, which was accompanied by an increase in blood pressure. The subsequent physical impact is pain. The mandatory swab obligations carried out by participants are a cause of pain, which is necessary for them to continue undergoing the hemodialysis process.\n\n“My body feels heavy. They usually remove three litres of fluid, but now they only remove two or two and a half litres during the four-hour sessions” (P1).\n\n“My stomach is bloated, and my legs are swollen. They removed three litres before, but now it is only two” (P2).\n\nAnother physical impact reported by the participants was difficulty breathing, which was often the result of postponed or rescheduled hemodialysis sessions.\n\n“It gets really bad; I feel breathless, and it gets worse if I miss a session of hemodialysis” (P9).\n\n“Yes, I feel breathless, especially if I have not had hemodialysis for a while” (P12).\n\nThe subsequent physical impact observed was an increase in blood pressure due to anxiety over swab test results. Several participants experienced significant anxiety at the prospect of testing positive for COVID-19, which in turn led to elevated blood pressure. The following are quotes from some participants:\n\n“The swab test is what scares me, and it causes my blood pressure to rise. It is always on my mind, especially when waiting for the results—my results are coming out tomorrow, and I am so anxious” (P2).\n\n“After a swab, I feel uneasy. Before the pandemic, my blood pressure was normal. Now it often spikes. It is still high and rarely goes down” (P4).\n\nThe other physical impact is pain. This is a direct consequence of the mandatory swab, which participants must carry out in order to continue undergoing the hemodialysis process. The process of taking samples for swab examination, which occurs every 2-3 weeks, causes pain for some participants. The following statements from several participants illustrate this point.\n\n“The swab every 14 days hurts my nose” (P2).\n\n“This swab is really painful. It is only a matter of time before I start screaming” (P9).\n\nPsychological impact\n\nThe COVID-19 pandemic has also had a significant psychological impact on patients undergoing hemodialysis. The necessity of awaiting the results of the swab and the obligation to undergo continuous swabs has resulted in the patient experiencing disturbances to their sleep patterns, a sense of being a burden, and a perception of being under constant observation during the course of this pandemic. The majority of participants reported experiencing disturbances in their sleep patterns during the pandemic. However, during the current pandemic, these disturbances have been exacerbated due to concerns about the results of the swab. The majority of participants reported feeling burdened by the obligation to undergo swab tests. The obligation to undergo swabbing every 2-3 weeks necessitates that participants visit a hospital outside of their scheduled hemodialysis appointment and other scheduled examinations. The process of swabbing is quite intricate and time-consuming. The extended period is a significant burden for participants, particularly given their history of complications related to declining kidney function. One participant also reported a psychological impact resulting from the constant observation by nurses.\n\n“When it is close to the following swab schedule, I often have trouble sleeping. The stress and anxiety that come with the condition make it difficult for me to get the rest I need. As my stress levels rise, I find it even harder to sleep” (P8).\n\n“I’m so scared, I’m really worried. I hardly ever sleep at night. I’m always thinking about when the phone will ring, telling me I’m positive COVID-19” (P11).\n\nAnother psychological impact was the sense of being overwhelmed by the frequent swab tests. The necessity of attending the hospital outside of their regular hemodialysis schedule introduced an additional source of stress to an already challenging situation. The process of scheduling and undergoing the tests was found to be overwhelming by the participants, as evidenced by the following description:\n\n“It’s such a burden to have to do the swab every 21 days. The whole process—the route, the queue, registering, then seeing the doctor the next day, and so on—it’s exhausting” (P12).\n\nAnother participant echoed this statement:\n\n“The process of undergoing a swab is quite exhausting. It involves waiting in line, expressing dissatisfaction, sitting down, and then being called again, going to the emergency room, and finally, to the swab room. This cycle occurs every two weeks, and the fatigue associated with it persists” (P13).\n\n“It feels like I’m always being watched during this pandemic. I keep wondering when I’ll have to swab again” (P9).\n\nSocial impact\n\nAdditionally, several participants reported experiencing social impacts as a result of the pandemic. A reduction in social interaction and a sense of ostracism were among the social impacts experienced by participants. A reduction in social interaction has been observed among fellow hemodialysis patients in the hemodialysis unit. Other social impacts include instances of ostracism. Some participants were ostracised by their families and neighbours during the pandemic due to the assumption that they had contracted the COVID-19 virus from the hospital.\n\n“Upon arrival at the hemodialysis unit, I found it necessary to limit my interactions with others. I maintained a distance and focused on personal hygiene, such as cleaning my bed. The atmosphere was noticeably different from what I had experienced previously” (P2).\n\nThe pandemic also had a profound social impact on participants, particularly in terms of social isolation.\n\n“We feel like we’re at a distance from our friends. Before, we could forget about our illness by spending time with friends, but now we have to keep our distance” (P7).\n\nOthers were shunning another social impact. Some participants reported being avoided by their neighbours and family members due to fears that they might bring COVID-19 home from the hospital.\n\n“It’s frustrating when I visit neighbours, and they immediately leave when I arrive. I tell them I don’t have the virus, but they don’t listen. I have a swab test result every two weeks, but they ignore me” (P5).\n\n“People think the hospital is full of COVID-19, so when I come home from the hospital, they avoid me” (P7).\n\nEconomic impact\n\nAdditionally, several participants reported experiencing the economic consequences of the global pandemic caused by COVID-19 pandemic. The cost of living has risen for those who require hemodialysis therapy. The obligation to undergo swabbing procedures has resulted in an increase in the number of visits to the hospital by participants, necessitating the expenditure of funds on transportation. Furthermore, participants are required to bear additional costs associated with the procurement of personal protective equipment, including masks.\n\n“The issue is that wearing a mask is quite difficult. I believe masks are not meant to be used twice, so we have to replace them. If we’re on a tight budget, we have to use them twice. We used the first mask 2-3 times. It is much work. That’s why my husband is back in his hometown to earn money for hospital expenses” (P7).\n\nTheme 3: Coping mechanisms developed\n\nAdaptive coping\n\nAdaptive coping is the most prevalent coping strategy individuals employ in response to challenges encountered during the ongoing pandemic. Other coping adaptations employed by participants include spiritual strengthening.\n\n“I pray to God every day and night. Hopefully, we won’t get infected with COVID-19” (P11).\n\n“We are sick, and the swabs make us feel worse, so we keep praying that these swabs will stop soon\" (7).\n\nSome participants attempted to maintain a positive outlook despite the negative emotions they experienced during the pandemic.\n\n“I worry sometimes, but I know my immunity is good, so I just stay positive” (P4).\n\n“I try to stay calm and face everything head-on. This is not something that comes easily to everyone, so I tell my friends that maybe we’re being tested. Alhamdulillah, it gives me strength, so I stay motivated” (P5).\n\nAnother adaptive coping strategy was dietary change. Some participants modified their diets to forestall any complications before undergoing swab tests.\n\n“I’ve been trying to cut back on my fluid intake and improve my diet. I make sure to eat well every time I have a swab coming up” (P5).\n\n“I changed my diet because I used to eat oily and fried foods. Since the pandemic, I avoid them. I don’t eat ice cream anymore. I’m afraid of getting short of breath before the swab, so I limit my diet” (P7).\n\nFurthermore, participants demonstrated an ability to adapt to the revised schedule and the necessity of utilizing personal protective equipment (PPE) during hemodialysis.\n\n“When I first started, I was always late for my hemodialysis schedule in the morning, but after a couple of weeks, I got into a routine and stopped being late in the morning” (P1).\n\n“I have become accustomed to the new protocol. Initially, I found it unusual to be instructed to wear a mask, but I have since made it a routine practice. It is now unusual for me not to wear a mask at the hospital” (P14).\n\nMaladaptive coping\n\nWhile some participants employed adaptive coping strategies in response to the various challenges and difficulties encountered during the ongoing pandemic, others resorted to maladaptive coping mechanisms to deal with the pandemic’s multifaceted impacts. Some participants employed excessive prevention and withdrawal mechanisms as a means of adapting to the conditions of the pandemic.\n\n“I drank vitamin C, folic acid and played sports despite the rain. I drink honey and boiled ginger, which are high in potassium, but I do not care. The main thing is that it is clear: do not be exposed to COVID-19” (P3).\n\n“I slept with a mask on. My child asked why I wore a mask to sleep. I said it was because I was afraid of COVID-19. I also bought vitamins from the pharmacy because I was scared.” (P6).\n\nAnother maladaptive coping strategy observed was social withdrawal during hemodialysis. Some participants elected to withdraw from social interactions in order to circumvent the stigma associated with their condition. As individuals with end-stage renal disease, they were required to undergo hemodialysis two to three times per week at the hospital. However, the stigma associated with COVID-19 prompted them to avoid contact with others.\n\n“I do not want to be identified as a patient with COVID-19. When I am in the hospital, I do not talk to or touch other people” (P4).\n\n“I’d rather stay silent than explain myself. If people misunderstand, I accept it. I can’t change what they think” (P10).\n\n\nDiscussion\n\nStress during an infectious disease outbreak include fear and worry about health problems and worsening chronic health problems (CDC, 2020). Entire participants in this study also expressed various negative emotions, such as feelings of worry, fear, and suspicion, in line with research conducted by Xia et al. (2020), which shows the high level of psychological distress experienced by hemodialysis patients at the start of the pandemic, this was due to the high frequency of patients going to the hospital to undergo hemodialysis therapy and concerns about the transportation used. Other research that supports this argument conducted by Guerraoui et al. (2021), which shows the occurrence of anxiety and depression in hemodialysis patients in the early days of the pandemic due to fear of getting infected with COVID-19 due to the high incidence of COVID-19 and fear of transmission of COVID-19 to their family.\n\nAt the start of the pandemic, most participants were worried about COVID-19, causing participants to have difficulties accessing hemodialysis center. Hemodialysis schedule were overcrowding and limited health personnel in hemodialysis units which made this situation more challenging to prepare many special machines for hemodialysis patients with COVID-19 at the start of this pandemic (IRR, 2018). Some participants also felt worried about being ostracized if infected with COVID-19. Infectious diseases are usually associated with stigma and cause discrimination against this group of patients in society (Abdelhafiz & Alorabi, 2020). Pandemics like COVID-19 cause fear and anxiety, which can lead to social stigma that can ultimately lead to the occurrence of social avoidance (Turner-Musa et al., 2020). Common symptoms of COVID-19, such as fever, cough, and shortness of breath, were common symptoms that hemodialysis patients experienced before the pandemic (IRR, 2018). There are similarities in symptoms between COVID-19 and symptoms commonly experienced by hemodialysis patients, which also ultimately caused the emergence of suspicion among hemodialysis patients towards other hemodialysis patients.\n\nPrevious research shows that patients experienced feelings of worry and fear that hemodialysis can make them non-compliant with medication therapy, including non-compliance in undergoing hemodialysis therapy (Kimmel, 2001; Kimmel & Peterson, 2005). However, this is different from what was obtained in this study. Amid worry, fear, and suspicion at the start of the pandemic, most hemodialysis patients still stated they were trying to maintain their compliance in undergoing hemodialysis therapy. Participants stated that the impact of not undergoing hemodialysis is more significant than not undergoing hemodialysis due to their worries and fears about COVID-19. They depend on hemodialysis therapy to maintain continuity in their lives and prevent the emergence of various further complications due to their disease condition if they do not comply with medical therapy.\n\nExcessive emotional responses can cause negative behavior. COVID-19 is a new infectious disease that can cause anxiety and fear excessively, which can lead to dangerous behaviour (Ho et al., 2020). This study found that worry, fear, and suspicion experienced by participants in the early days of the COVID-19 pandemic led to the emergence of several negative behaviors from participants, such as hiding their health status and ignoring social ethics. Participants chose to hide their health status, mainly if they got symptoms that were similar to the main symptoms of COVID-19 or had a history of contact with families who have COVID-19 symptoms. They done it to avoid referrals to an isolation room and carrying out COVID-19 screening which could later have an impact on delay in the participant’s hemodialysis schedule. Therefore, if participants already have symptoms such as fever, cough, and shortness of breath, participants will chose to treat themselves. This argument is supported by research conducted by Villa et al. (2020), who stated that stigma can lead people from possibly suffering from COVID-19, hiding symptoms to avoid pressure from the surrounding environment. This can make patients who have mild symptoms to avoid treatment from the health unit and act as usual so as not to arouse suspicion about their condition. When a crisis or pandemic occurs, individual or community will look for information about what happened. However, if information from trusted sources or official news is limited, people will look for information on social media and other media, which the truth cannot be guaranteed . This can cause a negative emotional response in a society that tends to experience extreme fear and uncertainty and negative behaviour is often driven by fear and distorted risk perceptions (Torales et al., 2020). Research conducted by Wang et al. (2020a) stated that the dissemination of health information related to COVID-19, continuously updated and verified for accuracy by authorities or trusted parties, can reduce levels of anxiety, stress, and depressive symptoms in society. Therefore, the role of the nurse as an educator is vital.\n\nThe COVID-19 pandemic has impacted physical health, mental health, social life, and the economy. Patients with chronic diseases will experience many impacts, especially health problems during the COVID-19 pandemic caused by delays or difficulties in scheduling health services (Singh et al., 2021). WHO (2020) revealed that more than half of the countries affected by COVID-19 reported many disruptions to care services for patients with the disease. Chronic, especially those requiring routine or long-term treatment. It was found in this research that the COVID-19 pandemic had a physical impact on kidney failure patients undergoing hemodialysis due to delays and schedule changes in hemodialysis. The COVID-19 pandemic not only causes many physical health impacts, but it also has many mental health impacts (Pfefferbaum & North, 2020).\n\nThe mental health and psychosocial impacts of the COVID-19 pandemic may be more severe among people with chronic diseases. In the presence of chronic diseases, they are a group that can have severe complications if they infected by COVID-19, causing increased perceived stress and ultimately making worse their health problem (WHO, 2020). Participants also experienced various psychological impacts during the pandemic. High stress due to concerns about being positive for COVID-19 from the final swab examination results caused almost all participants to experience sleep disturbances, increased blood pressure, burden, and feeling shunned during this pandemic. The COVID-19 pandemic can have a long-term impact on the physical and mental health of hemodialysis patients. Currently, The World Health Organization (WHO) is actively trying to control and reduce the impact of this pandemic by identifying, testing, and treating infected patients and developing drugs, vaccines, and treatment protocols (WHO, 2020b). However, success in overcoming the pandemic cannot be confirmed (Kumar & Nayar, 2020). Chronic disease sufferers can face lifestyle disturbances due to the COVID-19 outbreak, physical activity, sleep, stress, and mental health, which need to be handled better (Kendzerska et al., 2021). Research conducted by Yang et al. (2021) shows a relationship between mental status changes and hemodialysis patients’ quality of life during the COVID-19 pandemic. Therefore, it is necessary to provide psychotherapeutic interventions during this pandemic to improve the quality of life of hemodialysis patients.\n\nHemodialysis patients also experience social impacts. Most participants stated there is decreased social interaction between fellow hemodialysis patients. Research conducted by Yang et al. (2021) also stated that there was increased social dysfunction in patients hemodialysis since the beginning of the pandemic. Therefore, hemodialysis nurses can create chat groups that are innovative, engaging, and easily accessible to hemodialysis patients and families.\n\nThe COVID-19 pandemic increases the cost burden on hemodialysis patients, mainly by supplying funds for purchasing personal protective equipment. Apart from that, swabs and other examinations are mandatory. The pandemic caused an increase in the frequency of hospital visits, this has increased the amount of personal protective equipment that must be prepared and increased costs for transportation. Research conducted by Lee et al. (2020) also shows that 90% of patients in hemodialysis are concerned about the economic impact and difficulties of finances during the COVID-19 pandemic. Adjusting swab examination schedules and other examinations with hemodialysis schedules may be a dialysis unit consideration. Reducing the frequency of going to the hospital can reduce transportation costs. Hemodialysis patients can simultaneously reduce the risk of exposure to COVID-19 both during travel and in the hospital.\n\nParticipants in this research also developed various coping strategies to deal with the various stressors experienced in the COVID-19 pandemic. Most participants used spiritual strengthening, thinking positively, and trying to accept and get used to it as adaptive coping mechanisms during the pandemic. Several previous studies also show that there are efforts to implement adaptive coping strategies in facing the COVID-19 pandemic. It is like relying on increased social support (Cao et al., 2020) and adopting preventive measures to offset or minimize health risks and finances brought about by COVID-19 (Wang et al., 2020a). Maladaptive coping refers to coping strategies associated with poor mental health outcomes and symptoms of higher levels of psychopathology, such as avoidance and emotional suppression (Compas et al., 2020). In this research, several participants also developed maladaptive coping during the pandemic, include taking excessive preventive actions and withdrawing hemodialysis to face various stressors during the pandemic. Several previous studies identified factors of demographics as a potential risk of implementing maladaptive coping strategies in dealing with the COVID-19 pandemic, such as age, gender, race, socioeconomic status, and the burden of being parents (Atchison et al., 2021; Clay & Parker, 2020). However, this study did not find a relationship between demographic data and participants’ maladaptive coping strategies. Therefore, differences in the participants’ personalities can be a factor in using coping strategies in this research. This is relate to the research conducted by Bacon & Corr (2020) and Carvalho et al. (2020) state that personality functions influence adaptive and coping strategies related to health problems during the COVID-19 pandemic.\n\nHow individuals face and deal with situations caused by COVID-19 can impact their mental, physical health and their willingness to participate actively in much-needed action (Brailovskaia & Margraf, 2020; Yang et al., 2020). The COVID-19 pandemic continues, and it is not known when it will end, including in this continuing era. According to Roy’s theory, during the COVID-19 pandemic, various stimuli, such as the various impacts experienced by hemodialysis patients, can influence the adjustment or adaptation of hemodialysis patients to their disease conditions. The research results show that most participants have attempted to adapt to various aspects of the impact of the COVID-19 pandemic, this can be seen from the participants’ efforts to maintain adherence to hemodialysis therapy amidst worry and fear against COVID-19. Most participants have also tried to build adaptive coping strategies in dealing with the various impacts of the COVID-19 pandemic. Therefore, hemodialysis nurses are expected to continue to support participants who strive to implement adaptive coping strategies and can help other participants experiencing maladaptive coping strategies to adaptive coping. Individuals with positive coping strategies usually show fewer symptoms of anxiety and stress (Moccia et al., 2020; Wang et al., 2020b).\n\nAdditionally, hemodialysis nurses are expected to educate hemodialysis patients about appropriate coping skills that can significantly impact how they view their condition, the severity of symptoms, and psychological stress related to the COVID-19 pandemic. Understanding strategy coping is very important to support the patient’s coping efforts. Apart from that, it is necessary to monitor the patient’s coping strategies and evaluate the patient’s psychological status periodically so that the nursing care provided can be adjusted to current conditions and help hemodialysis patients to remain able to adapt in this pandemic situation so that their quality of life can still be maintained.\n\n\nConclusion\n\nResults of research on end-stage renal disease patients undergoing hemodialysis in the era of the COVID-19 pandemic illustrate three main themes, consist of (1) the emergence of various responses to the beginning of the pandemic both through emotional and behavioral responses, (2) the emergence of various impacts during a pandemic such as physical, psychological, social and economic impacts and (3) the existence of coping strategies that were built during the pandemic, namely adaptive and maladaptive coping. These findings showed that end-stage renal disease patients underwent hemodialysis in the COVID-19 pandemic era requires support from healthcare providers in hemodialysis units to overcome various problems and impacts resulting from the COVID-19 pandemic.\n\nDue to the COVID-19 pandemic, interviews were limited to face-to-face sessions with 4 participants and phone interviews with 11 participants, based on their comfort levels. Health protocols during face-to-face interviews sometimes led to unclear responses, requiring follow-up questions, which may have affected the depth of the data. Additionally, the reliance on phone interviews limited the observation of non-verbal cues, potentially impacting the richness of the insights. The study’s findings are also based on a specific sample from two hospitals in Indonesia, which may limit their generalizability to other populations and contexts.\n\nClinical practice implications\n\nHealthcare providers, especially hemodialysis nurses, should offer holistic care addressing both physical and psychological needs to reduce patients’ anxiety and stress.\n\nHealth policy implications\n\nHealth policies should prioritize preparedness for future pandemics by ensuring flexible care schedules and maintaining access to essential treatments, minimizing disruptions to patient care in times of crisis. Continuous evaluation of healthcare systems’ resilience is necessary to protect vulnerable patients in any future public health emergencies.\n\nResearch implications\n\nThis study is a valuable reference for developing bio-psycho-social interventions tailored to chronic kidney failure patients receiving hemodialysis, particularly during pandemic conditions. Further studies are needed to explore factors influencing patients’ coping strategies and to evaluate the long-term effects of the pandemic on the quality of life of dialysis patients.\n\n\nEthical considerations\n\nResearch ethics were ensured through the approval of the Faculty of Nursing Ethics Committee at the University of Indonesia, documented under ethical approval number: SK-15/UN2.F12.DI.2.1/ETIK 2021, dated February 3rd, 2021. The researchers provided explanations regarding the procedures, objectives, benefits, potential risks, and the rights and responsibilities of participants through a research information sheet. Participation was voluntary, as indicated by the signing of informed consent. Participants were also assured that their involvement was voluntary and were informed of their right to withdraw from the study at any time without facing any penalties.",
"appendix": "Data availability\n\nThe interview transcripts cannot be publicly shared because the data contain sensitive information that could potentially identify the participants. The restriction is a guideline set by the ethics committee and included in the informed consent that participants have agreed to. Access to the data is restricted to protect participant confidentiality. Any data access requests must be reviewed and approved by the authors and will only be granted under conditions that ensure participant anonymity. All transcripts are in Bahasa. Those interested in reading the summary report, including quotes, may contact the corresponding author (dewiyantitodinguh@gmail.com) for translations of the requested sections.\n\nFighshare: COVID-19 pandemic: A Qualitative Study. figshare. Journal contribution, https://doi.org/10.6084/m9.figshare.27310995.v2 (Toding, 2024).\n\nThis project contains the following extended data:\n\na. Research explanation: This section provides participants with details on the study’s objectives, methods, potential benefits, risks, and their rights. It also explains data usage and protection measures, along with how participants can ask questions or choose to withdraw from the study if necessary\n\nb. Informed consent: this is the voluntary consent participants provide after being fully briefed on the study’s details, as outlined in the research explanation provided to them.\n\nc. Reporting guidelines: we used COREQ checklist\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThis study was successfully conducted with the support of various parties. We want to thank the hospitals where the study was carried out and the Faculty of Nursing, University of Indonesia. 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}
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[
{
"id": "342952",
"date": "16 Jan 2025",
"name": "Natasha Hubbard Murdoch",
"expertise": [
"Reviewer Expertise Nursing",
"pandemic experiences for nursing disciplines including educators",
"practice",
"administration in licensed practical nursing",
"psychiatric nursing and registered nursing in addition to the unregulated nursing pandemic experience for continuing care assistants or personal support workers"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis qualitative descriptive study presents themes on the experience of 15 patients with end-stage renal disease in Indonesia during the COVID-19 pandemic. This nursing research focused on those patients in hemodialysis. The researchers presented a balanced view of the concerns hemodialysis patients face in comparison to the exacerbated concerns because of the pandemic. The themes described the emotional and behavioral responses to the pandemic, the physical, psychological, social and economic impacts, and the adaptive and maladaptive coping mechanisms of having hemodialysis during COVID. The focus of the discussion was on how nurses can ensure holistic provision of care to specifically support coping skills. This research is unique in that it presents findings from a nursing specialty that provides critical insight into the relationship with patients and families experiencing end-stage renal disease.\nMajor comments: Please describe qualitative descriptive design more thoroughly and rationalize its use for this particular study.\n“The determination of participants is based on data adequacy” (p. 3). Clarify this decision, specifically what data adequacy means. A reference is required. “Once data saturation is reached, whereby no new insights or information can be derived from the participants” (p. 3). The Bradshaw et al. reference provides a great description of the rationales for data saturation, but the argument for its use was not provided in this article. Considering that participants were recruited from two hospitals using data collection methods differently, explain how saturation can be affected or met.\nThere were two instances where the principal researcher noted they gained practical experience with data collection: 1) “She has also practised conducting interviews with hemodialysis patients, though not with the specific participant” (p. 3), and 2)“The outcomes of these preliminary interviews were documented and reviewed with the supervisors” (p. 4). These are great acknowledgements to the school, but unless they refer specifically to data that contributes to this study, these comments should be removed. In acknowledgment of the relationship with the research team members, the authors may choose to note this in a section about rigor.\n“Roy’s theory,” (p. 11). The authors allude to the integration of nursing theory late in the paper without any explanation or reference. At minimum, cite. However, it would be prudent to include a description of Roy’s theory and how the lens is employed during data analysis in the methodology section. This would also add some credence to what is presented in the discussion.\nThis sentence in the discussion is a random reference to ‘personality’ that has not been addressed anywhere else in the paper. This must be addressed earlier, or it must be addressed more thoroughly prior to bringing it up in this way. “This is relate to the research conducted by Bacon & Corr (2020) and Carvalho et al. (2020) state that personality functions influence adaptive and coping strategies related to health problems during the COVID-19 pandemic.” (p. 11)\nThe references in the discussion could be updated to reflect a more recent reality of COVID. The authors may consider writing a reflective section on how the evidence has changed from the time of this study to what has since been reported for this specialty.\nMinor comments: The paper requires a rigor section which is a required component of qualitative research. Rather than presenting this as a student paper, the following statements should be reworded to reflect rigor criteria: 1) “The research proceeded only after obtaining supervisor approval to continue the interviews.” (p. 4), and 2) “Two experts oversaw the research, and its validity was assessed through a thesis examination involving two expert examiners and nursing master’s students as reviewers. This comprehensive process ensured the research’s quality and reliability.” (p. 4), and 3) “The findings were shared with participants for verification.” (p. 4). Please ensure to follow a rigor framework such as Lincoln and Guba (or others).\nAllusion to a purpose of providing suggestions for nursing interventions but the implications section is superficially written. Articulate specific clinical practice interventions. “Therefore, the researchers aimsto capture these perspectives to develop more suitable nursing interventions for them..” (p. 3)\nSubtheme, physical impact. End of page 6. Incongruent narrative in relation to the data provided. The pain of swabs is not as significant as the pain of fluid build-up. “The subsequent physical impact is pain. The mandatory (p. 6) and, “swab obligations carried out by participants are a cause of pain, which is necessary for them to continue undergoing the hemodialysis process” (p. 7)\nGeneral writing concerns: The paper requires an edit for English spelling, grammar, and structure. The following are the suggestions I can offer.\n“aims” (p. 1) aimed – the study is done Repetitive sentence twice in a row. “As a risk group, hemodialysis patients have a fear of not being able to face COVID-19 if they are exposed. As a high-risk group, hemodialysis patients fear they may not be able to cope with COVID-19 if exposed (WHO, 2020a).” (p. 3)\nQuite a few occurrences where words, sentences, or concepts are repeated multiple times in a sentence or paragraph. For conciseness, please reword. : “Hemodialysis patients must go to the unit hemodialysis 2-3 times per week and undergo 4-5 hour hemodialysis process, further increasing the patient’s risk of being exposed to COVID-19” (p. 3) : “In addition, some patients’ schedules have been modified as a result of the hemodialysis unit’s efforts to optimize the hemodialysis schedule.” (p. 6) : “The majority of participants reported experiencing disturbances in their sleep patterns during the pandemic. However, during the current pandemic, these disturbances have been exacerbated due to concerns about the results of the swab.” (p. 7) :“A reduction in social interaction and a sense of ostracism were among the social impacts experienced by participants. A reduction in social interaction has been observed among fellow hemodialysis patients in the hemodialysis unit. Other social impacts include instances of ostracism. Some participants were ostracised by their families and neighbours during the pandemic due to the assumption that they had contracted the COVID-19 virus from the hospital.” (p. 8)\n“also a physical” (p. 6) This sentence requires rewriting or a supporting reference. Is there evidence that BP increases in end-stage renal clients ONLY in relation to anxiety about COVID? Statements such as these need to be well cited.\nConfusing wording or edits : “face patients” (p. 3). Clarify. “aimsto” (p. 3) aimed? “and proficient” (p. 3) missing a word “and telephone” (p. 4) This sentence is unclear. “in relation to” (p. 5) because of? Anxiety requires a cause/effect wording “arises” (p. 5) arose – past tense “It should be noted that swab results were not available.” (p. 6) This sequence of sentences, the one before and after, do not relate to this one. Please describe whether swab results, when not ready on time, affected schedules. This is a set of confusing statements in relation to the sequence of swabbing that seemed to be regularly scheduled at every two to three weeks. This translation within a participant quote requires clarification. Not sure a patient would say, expressing dissatisfaction. “expressing dissatisfaction” (p. 8)\nCurious how maladaptive coping mechanisms is described since it has not been defined in the methods nor described in the discussion. “others resorted to maladaptive coping mechanisms to deal with the pandemic’s multifaceted impacts.” (p. 9) “include” (p. 9) missing wording “Entire” (p. 9) all? “which” (p. 9) delete? “Hemodialysis schedule were overcrowding” (p. 10) reword this sentence “negative behavior” (p. 10) What is negative behaviour? This needs rewording. Risky? Emotional responses are protective so it’s difficult to put a qualifier to how it is expressed without knowing the demographics and context. “They done it t” (p. 10). Not grammatically correct “Therefore, if participants already have symptoms such as fever, cough, and shortness of breath, participants will chose to treat themselves.” (p. 10). This statement is not supported by evidence, nor is it explained well in the ensuing sentences. What does this mean in relation to hemodialysis treatment and/or COVID?\n“When” (p. 10). This word delineates the start of a new paragraph and new set of commentary on misinformation. “Chronic, especially those requiring routine or long-term treatment.” (p. 10). Not a sentence “they infected” (p. 10) sentence structure “The World Health Organization (WHO)” (p. 10). The acronym was used in a previous paragraph. This both does not apply and does not reflect the evidence from the pandemic. This is an example where references need to be updated to acknowledge when the data was collected, but how the paper impacts current reality. “actively trying to control and reduce the impact of this pandemic by identifying, testing, and treating infected patients and developing drugs, vaccines, and treatment protocols (WHO, 2020b). Purpose of this statement? “However, success in overcoming the pandemic cannot be confirmed (Kumar & Nayar, 2020).” (p. 11) This is a random intervention that is not written within other options or within its own section. Provide an evidentiary citation that this is an option. “Therefore, hemodialysis nurses can create chat groups that are innovative, engaging, and easily accessible to hemodialysis patients and families.” (p. 11) Some of the expenses suggested by the authors are minimized in statements such as this. Economic impacts certainly included PPE, swabs, and transportation, but probably also included changes to wages, benefits, ability to access appropriate diets… “mainly by supplying funds for purchasing personal protective equipment. Apart from that, swabs and other examinations are mandatory.” (p. 11) The spiritual connection was a surprise under stressors. This phrase in particular is colloquial. “get used to it” (p. 11) What is like? “It is like” (p. 11) Not sure that parenting should be presented as a burden. “and the burden of being parents” (p. 11) Starting with the sentence “Understanding” (p. 11) what is strategy coping? “consist” (p. 12) that consist of? “underwent” (p. 12) Who underwent?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "346186",
"date": "05 Feb 2025",
"name": "Mehtap Kavurmaci",
"expertise": [
"Reviewer Expertise The research results are important as they will form the basis for precautions to be taken for HD patients in possible future pandemics."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors,\nThe findings of this research examining the experiences of hemodialysis patients during the COVID-19 pandemic offer applicable recommendations for nursing practice and health policies. The data were collected using the in-depth interview method. The research results show that hemodialysis patients developed adaptive coping strategies during the COVID-19 pandemic, but their need for support from healthcare providers continues.\nThe recommendations that I think will contribute to the research are listed below.\n1- It is recommended to provide information about adaptive coping strategies in the introduction section of the research. This information will contribute to the understanding of the findings by the readers.\n2- The fact that the research is limited to only two hospitals may limit the generalizability of the findings. However, it was appropriate that you stated this in the limitations section.\n3- The phone interviews conducted due to COVID-19 may have missed some important observations that could have been obtained in face-to-face interviews. Please state this situation in more detail in the limitations section, including how many people and how many phone interviews were conducted.\n4- There are studies in the literature examining the effects of Covid-19 on Hemodialysis patients. To enrich the discussion section, I recommend that the resources I suggested be read and used in the discussion section and added to the references.\n(Kosunalp N, Kavurmaci M. Determination of anxiety, depression, avoidance, and obsessions experienced by hemodialysis patients during the COVID-19 period. Ther Apher Dial. 2023 [Ref - 1];27(6):1070–8. https://doi.org/10.1111/1744-9987.14031)\n(Nadort E, Rijkers N, Schouten RW, Hoogeveen EK, Bos W, Vleming LJ, et al. Depression, anxiety, and quality of life of hemodialysis patients before and during the COVID-19 pandemic. J Psychosom Res. 2022 [Ref - 2];158:110917. https://doi.org/10.1016/j.jpsychores.2022.110917)\n(Dehghan M, Namjoo Z, Mohammadi Akbarabadi F, Fooladi Z, Zakeri MA. The relationship between anxiety, stress, mental health and mindfulness in patients undergoing hemodialysis: A survey during the COVID-19 outbreak in Southeastern Iran. Health Sci Rep. 2021 [Ref - 3];4(4):e461. https://doi.org/10.1002/ hsr2.461)\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1404
|
https://f1000research.com/articles/13-456/v1
|
07 May 24
|
{
"type": "Research Article",
"title": "Delirium management and current practice among Intensive Care Units Doctors, Khartoum",
"authors": [
"Sheema Hamid Seidna Hamid",
"Ghada Omer Hamad Abd El-Raheem",
"Hana Eltayeb Salih Elamin",
"Mudawi Mohammed Ahmed Abdallah",
"Sheema Hamid Seidna Hamid",
"Hana Eltayeb Salih Elamin",
"Mudawi Mohammed Ahmed Abdallah"
],
"abstract": "Delirium is a brain dysfunction characterized by attention and cognitive disturbances in a fluctuating manner. The international guidelines recommend daily screening for delirium. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) are the most commonly used methods for assessing delirium. This study aimed to identify barriers and gaps in knowledge and practice. This was a hospital-based Cross-Sectional study. Stratified random sampling was used in this study. 72 ICU doctors were randomly selected. Statistical analyses were performed using IBM SPSS version 23. Descriptive data were presented, and the chi-squared test was used to determine the associations among variables. Statistical significance was set at p < 0.05. More than 70% of the doctors were ≤ 30 years of age and female. A total of 69.4% of the participants had < 1year of experience. In total, 94.4% of the participants worked in medical ICUs. Less than 20% of the doctors used delirium assessment tools, with a statistically significant difference based on experience (p=0.012). Delirium was not regularly assessed in 13.9% of the patients. Non-pharmacological management was applied by 76.4% of doctors, and communication with patients was the most frequent (75%). Haloperidol was the most commonly used drug (83.3%). A total of 40.3% of doctors did not stop delirium medication on ICU discharge. A regular delirium assessment was performed. However, the use of validated assessment tools is uncommon. Nonpharmacological management of delirium is important and is mostly performed. Our doctors prescribed antipsychotics for the treatment of both forms of delirium, and almost half of them did not stop the medications on ICU discharge. Medication reconciliation and contact with the next in-charge of the patients are important.",
"keywords": [
"Delirium",
"CAM-",
"ICDSC",
"critically ill patients",
"ICU",
"current practice",
"Intensive Care Units",
"Doctors.ICU"
],
"content": "Background\n\nDelirium is a state of brain dysfunction characterized by attention and cognition disturbances in a fluctuating pattern,1–7 with an acute onset of confusion and decline in cognitive ability, often occurring in hospitalized patients.8 Delirium is related to many factors, such as the pre-existing vulnerable state of patients or medication-induced delirium that occurs during hospital stay.9 Delirium is a common disorder among intensive care unit (ICU) patients because of many factors such as old age, multiple medical interventions, and critical illness severity.5,10 Critically ill patients who are complicated with delirium, in addition to their critical illness, have been associated with prolonged mechanical ventilation (MV), longer hospital and ICU stays, and increased mortality.3,4,6,8,11–13 The severity of adverse delirium outcomes was associated with the duration of delirium; the longer the duration, the worse the outcomes.11 Prolonged delirium in the ICU is considered a risk factor for developing post-intensive care syndrome, which is characterized by worsened or new impairments in cognitive, physical, and mental health.12 Acute delirium can persist for a few hours; however, it can persist for weeks to months after hospital discharge.14 Clinically, delirium can be hyperactive or hypoactive. In the hyperactive form, agitation is prominent, with frequent aggression and risk of self-harm. In the hypoactive form, the patient presents with a low level of consciousness, which is usually prostrate and uncommunicative. A mixed form may also occur with alternation between the two poles.14\n\nIts incidence varies widely; however, it has a high rate of 70–87%.3,6,8,11,12,15,16 Although delirium is common, it is preventable. Prevention or early management of delirium is crucial to reverse the delirium state and minimize adverse clinical outcomes.7,11\n\nThe nature of the underlying critical illness, as well as the lack of any verbal communication among ICU patients, poses a difficulty in delirium assessment in the ICU.5 Furthermore, delirium is associated with long-term cognitive impairments.8,17 Systematic assessment of delirium among ICU patients is considered a very important approach to deliver patient care and allows clinicians and other healthcare staff to detect delirium at an early stage.1,2\n\nFrom another perspective, patients with delirium are more likely to bear increased healthcare costs than those without delirium.12,15,17\n\nManagement of delirium might be challenging for ICU clinicians, as an established treatment plan is yet lacking.17 International guidelines recommend daily screening for delirium using validated delirium assessment tools.18 Several methods have been developed and validated to assess delirium in patients in the ICU. Of these tools, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) are the most commonly used for delirium assessment.19 In the CAM-ICU, four features were screened at a single point in time. The ICDSC has a screening checklist composed of eight features.16,18 These are the most frequently used tools for delirium screening.19 Furthermore, these instruments could also be used in patients with primary neurological injury, as growing evidence suggests.20\n\nIn particular, screening is mandatory for patients at moderate to high risk of delirium.18\n\nBarriers and gaps in practice were addressed by assessing the current status to identify the areas that need focusing on.21 Several studies have focused on delirium assessment by clinicians.3,18,22 In Sudan, no studies have been conducted in the ICU, particularly regarding delirium. This study assessed the current status of ICU doctors’ knowledge and practice of ICU doctors about delirium. This study aimed to identify barriers and gaps in knowledge and practice.\n\n\nMethods\n\nA hospital-based cross-sectional study was conducted to assess the knowledge and practices of intensive care unit doctors at the Military Hospital of Khartoum State, Sudan.\n\nThe Military Hospital is a complex of seven specialized hospitals totalizing 722 beds and 8 ICUs. The ICUs that met the inclusion criteria were involved in the study; neonatal and maternal ICUs were excluded from the study.\n\nA stratified random sampling technique was used to select 72 participants in proportion to the type of ICU: medical, surgical, and cardiac ICU, after excluding all administrative staff.\n\nThe outcome variables were the knowledge and practices of intensive care unit doctors. The related factor to the outcome variable was the years of experience of the participants.\n\nThe characteristics of the participants were reported as categorical variables; age, gender, ICU type and years of experience. Knowledge and practice of participants were assessed through closed questions entered as categorical variables.\n\nPotential source of bias was that the study depended on the self-reporting of the participants through filling the questionnaire.\n\nThe formula for the known population was used to select the sample size for each stage. The equation of known population was used to estimate the sample size: n=N/1+Nd2, where n is the estimated sample size, N is the total number of doctors in each ICU, and d is the degree of accuracy set at 0.05.\n\nAll variables included in the study were quantitative; they were handled in the analysis as categorical variables.\n\nThe Statistical Package for Social Sciences (SPSS version-23) was used to describe and analyze the data. Descriptive data are presented. Statistical analysis was performed using the chi-square test to determine the associations among variables. All tests were considered statistically significant at p < 0.05.\n\nThe ethics committee of Omdurman Islamic University reviewed and approved the proposal on 28.May.2021 after full board review (IRB name: Omdurman Islamic University Ethics Committee, Reference number: 2021/2). Approval from the Military Hospital was obtained and authorization to implement the research was granted by the administration of the ICUs. All methods were performed in accordance with the relevant guidelines and regulations of the Declarations of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Participants were informed about the research objectives and signed written informed consent was obtained from each participant prior to data collection. They were assured about their confidentiality through the use of an anonymous research tool and that the data collected from each of them were not to be used for any purposes other than those assigned to the research. Participants were free to accept or reject participation in this study.\n\n\nResults\n\nSeventy-two intensive care unit (ICU) doctors were assessed for their current knowledge and practice towards delirium among critically ill patients. Most doctors (70.8%, 51/72) were aged 30 years or less, and 86.1% (62/72) were female. On assessing experience, 69.4% (50/72) had less than one year of experience. Most doctors (94.4%, 68/72) had been working in medical ICUs. Table 1 below illustrates the demographic characteristics of the study participants.\n\nThe knowledge and practice of ICU doctors was assessed with regard to delirium. 38.9% of doctors were aware of delirium assessment tools, while 61.1% (44/72) had no knowledge of delirium assessment tools. Of the ICU doctors, 76.4% (55/72) stated that the non-pharmacological approach was their first-line management, whereas 22.2% (16/72) chose the pharmacological approach as shown in Table 2 below.\n\nAs for ICU doctors, the delirium assessment tools used were CAM-ICU (18.1%, 13/72) and ICDSC used by only one doctor. Signs and Symptoms were used by (76.4% (55/72) of the patients for delirium assessment (Table 2). The frequency of delirium assessment varied among doctors; 40.3% (29/72) of the doctors assessed delirium every 8-12 hours, while 45.8% (33/72) assessed delirium every 24 h. In contrast, 13.9% (10/72) of the doctors did not regularly assess delirium in critically ill patients (Table 2).\n\nMoreover, the practice of doctors towards delirium management was assessed. More than half of doctors used antipsychotics to manage agitation and delirium (54.2% and 69.4%, respectively). This was followed by sedatives prescribed by 33.3% (24/72) of doctors to treat agitation. For delirium, sedatives were prescribed by 20.8% (15/72) of doctors. Doctors were asked about their practice towards stopping delirium medications for patients on ICU discharge; 56.9% (41/72) of them stopped medications on discharge, while 40.3% (29/72) did not stop them from patients upon ICU discharge (Table 2).\n\nTen doctors reported that delirium assessment might be irregular for ICU patients. They were asked to report their reasons for not regularly assessing delirium. Only five doctors mentioned the reasons for this. The first reason was that only after the patient developed signs and symptoms, reported by two doctors, difficulty in assessment was the reason for one doctor, and a high workload was reported by 1doctor. Additionally, the use of family member support was the reason for one doctor.\n\nDoctors were asked to report their reasons for not using the nonpharmacological approach in their delirium management. The lack of knowledge about the non-pharmacological approach was the reason for this.\n\nThe most frequent nonpharmacological intervention used by ICU doctors for delirium management was communication with patients to prevent confusion. This was illustrated in Figure 1 below. This approach was used by 75% of the doctors. The second most common approach was early mobility of ICU patients, reported by 22.2% of doctors. Reducing nighttime sleep disturbances was used by 18.1% of the doctors. Benzodiazepine use was reduced by 6.9% of ICU doctors (Figure 1).\n\nThe doctors were asked to identify the pharmacological agents used for delirium treatment. As shown in Figure 2 below, the most commonly used agent was haloperidol, which was prescribed by 83.3% of the ICU doctors to treat delirium. The second most commonly used agent was olanzapine (5.6%), followed by a combination of olanzapine and haloperidol (4.2%). On the other hand, resperidone and quetiapine were prescribed by only 1.4% of the doctors (Figure 2).\n\nWith regard to the experience of doctors, their knowledge was assessed to determine if there was any difference in knowledge about delirium between experienced and non-experienced doctors. Doctors were grouped into two groups based on their years of experience: ≤2 years of experience and >2 years of experience. Interestingly, there was no statistically significant difference in ICU doctors’ knowledge about delirium tools and first-line treatment between experienced and non-experienced doctors (p= 0.059 and p=0.797, respectively).\n\nDoctors’ practice was assessed based on their experience. Among the 13 doctors who used the CAM-ICU as an assessment tool for delirium, 53.8% had >2 years of experience. Among the 55 doctors who assessed delirium using no tool and only by signs and symptoms, 85.5% had less experience (≤2 years). This difference in practice was statistically significant between experienced and less experienced doctors (p=0.012).\n\nRegarding the frequency of delirium assessment, no statistically significant difference was found between doctors based on their years of experience (p=0.636). In addition, no difference in practice towards agitation and delirium treatment was found among doctors based on their experience (p=0.496 and p=0.246, respectively). In addition, stopping delirium treatment at ICU discharge did not differ between doctors with different years of experience (p=0.121). Table 3 below details all the percentages of doctors with different experiences and practices towards delirium.\n\n* Statistically significant.\n\n\nDiscussion\n\nDelirium is common disorder among ICU patients.3,6,8,11,12,15,16 Doctors and nurses are direct healthcare providers for critically ill patients. In addition to nurses, doctors are involved in delirium assessment and reporting, as mentioned by Pisani et al.5 Lack of knowledge among staff has been reported as one of the individual barriers3; hence, our study tangled the knowledge of doctors.\n\nSociety of Critical Care Medicine recommended delirium assessment for all patients in the ICU through the use of a validated assessment instrument.4,5 However, in our study, most doctors (76.4%) did not use any specific tools for delirium assessment and relied on signs and symptoms alone. As in the study by Depetris et al., 57% of doctors did not use any specific tool for delirium assessment.18 Delirium was usually assessed using either the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC).7,23 Although the usefulness of the Confusion Assessment Method for the ICU (CAM-ICU) for delirium detection has been documented in recent studies,5,16 only 18.1% of our participants used CAM-ICU for delirium assessment. Nevertheless, ICDSC was used by only 1.4% of the doctors. Interestingly, in a systematic review, the CAM-ICU was the tool used for assessing delirium in 65% of delirium clinical trials, while the ICDSC was used in only 6% of the trials.6 In a meta-analysis study, both the CAM-ICU and ICDSC could be used to screen for delirium and diagnose it. However, the study favored CAM-ICU as ICDSC showed lower specificity and sensitivity than CAM-ICU.19 This was the case among our study participants, as only 1.4% used the ICDSC in assessing delirium, while 18.1% used the CAM-ICU tool. Comparatively, in a national multi-center study in China, 34% of doctors used delirium tools; of these, CAM-ICU was the most commonly used (83%) tool.22 Nevertheless, in another study, CAM-ICU was used by 27.5% of doctors, while ICDSC was used by 5%.18\n\nPresence of delirium among ICU patients must be assessed every 8 hours or at least every 12 hours.7,23 Less than half of the ICU doctors (40.3%) in our study assessed delirium every 8-12 hours, which was the practice in 60% of the clinical trials of delirium, as reported by Colantuoni et al. Furthermore, 45.8% of our doctors assessed delirium daily, which was higher than that reported (35%) by Colantuoni et al.6 Only 13.9% of our doctors had no regular assessments for delirium; this was the case for 30% of physicians in a multinational study.18 Among our study participants, one of the reasons for irregular delirium assessment was increased workload. This issue has been interpreted as an environmental barrier, especially among ICU staff.3 This issue was addressed in a study recommended that, in such case of limited resources, delirium management strategies may be prioritized for patients with high risk of delirium.7 In our study, the association between ICU doctors’ practice and their years of experience was studied. A statistically significant difference (p=0.012) was found in delirium assessment. Contrary to the study by Wang et al., there was no statistically significant difference (p=0.074) between experienced and less-experienced clinicians.22\n\nDelirium preventive measures are important for all ICU patients.7 This was the case for most of our doctors; however, two doctors reported that they had not conducted such measures unless the patient had developed signs and symptoms of delirium.\n\nThe non-pharmacological approach to delirium management (treatment and/or prevention) is the preferred approach.23 It was the first-line choice for 76.4% of the doctors in our study, which was higher than the percentage (22.5%) reported by Depetris et al.18 Communication with ICU patients to prevent confusion was the most frequent nonpharmacological approach applied by ICU doctors in our study (75%). This approach was discussed in a systematic review by Deemer et al. assessing early cognitive interventions for delirium in ICU patients.12 Moreover, participation of family members in delirium prevention strategies could be complementary to the communication interventions performed by doctors and nurses.12 In our study, this approach of using family member support was practiced by a single doctor. Sleep and circadian rhythm regulation among ICU patients was a targeted therapy approach for these patients24; however, it was applied by only 18.1% of our doctors. Another important risk factor for delirium was the use of benzodiazepines.15,23 Midazolam is the most commonly used sedative for ICU patients, prescribed as high as 72%–90.5% of sedatives.15,18,25 Hence, reducing their use is considered an important non-pharmacological approach for the prevention of delirium in critically ill patients.23 However, among our ICU doctors, only 6.9% adopted a reduction in benzodiazepines. Surprisingly, sedatives were used by 20% of our doctors to manage delirium and midazolam was one of the agents used by clinicians in China (31%) for treating delirium.22 This issue needs to be addressed because the use of sedatives for patients with delirium worsens the case and their use should be reduced.16,23\n\nBased on a systematic review by Barbateskovic et al., evidence for the use of pharmacological interventions in the management and prevention of delirium is sparse or poor.26 Nonetheless, this approach is not superior to delirium management.9 The pharmacological approach for delirium treatment was used as the first-line management in 22.2% of our study participants. This was higher than reported (2.5%) in a multi-national study.18 Antipsychotics were the most commonly used agents (69.4%) among our study doctors. Haloperidol was the most commonly used agent among ICU doctors (83.3%) for delirium treatment. This was consistent with a cohort study that used haloperidol alone in combination with clonidine.17 Furthermore, studies have reported that haloperidol use was the highest in patients with delirium (30%, 43.3%).4,22,26 The second most commonly used agent in our study was olanzapine (5.6%), similar to that reported (5.9%) by Swan et al.4 In contrast, quetiapine and risperidone were used by only 1.4% of our study participants, which was much lower than the frequencies reported by Swan et al. (12.7% and 5% respectively).4\n\nNot to forget that, delirium clinically has two states; hyperactive state mostly characterized by agitation, besides the hypoactive state,14 our study assessed current practice of doctors towards agitation treatment. More than half of the study participants (54.2%) prescribed antipsychotics for agitation treatment, while 33.3% prescribed sedatives. This practice of our doctors was not in line with recommended treatments, as sedatives were considered treatment agents for agitation.23\n\nContinuation of delirium medication after ICU discharge was common (50.2%), as per a previous study.27 Of our doctors, 40.3% had not stopped delirium medications on discharge, which was lower than that reported above.27 However, continuation of such medications beyond the hospital stay could lead to harmful and deleterious events, and medication reconciliation is crucial in such cases.23\n\nThe limitations of our study were the lack of a comparison between doctors’ practice and nurses’ practice. Furthermore, the data collection tool was not validated using Cronbach’s reliability test. Although this study was a multi-center study, selection bias might be a risk, as we focused on the Hospitals of the Military section as they were larger and more populated.\n\n\nConclusions\n\nLess than half of ICU doctors assessed delirium every 8-12 hours. Non-pharmacological preventive measures were applied by the majority of participants (976.4%). Communication with patients is important for delirium prevention, as was done by most of the study participants. However, the involvement of family members in communicating with ICU patients is an important approach; yet, it is only applied by one doctor. Delirium assessment tools were used by less than 20% of the ICU doctors. Delirium may fluctuate between agitation and hypoactive states. More than half of the ICU doctors prescribed antipsychotics for the treatment of both forms. This was not the case; sedation is the preferred approach for agitated patients. Only 33.3% of the participants were prescribed sedatives to treat agitation. Medication reconciliation and contact with the next in-charge of the patients must be conducted to reduce the use of these medications after hospital discharge.\n\nInstead of using signs and symptoms alone, ICU staff should focus on the use of delirium assessment tools. Non-pharmacological preventive measures must be implemented for all ICU patients, especially those with a high risk of developing delirium. The involvement of family members in communicating with ICU patients should be encouraged as a complementary approach to prevent delirium. A more frequent assessment of delirium is desirable among healthcare staff: 8 hours or 12 hours instead of once-daily assessment. Delirium may fluctuate between agitation and hypoactive states. Treatments for each form must be established by ICU doctors.\n\n\nDeclarations\n\nThe proposal was reviewed and approved by the Ethical Committee of Omdurman Islamic University. The ethics committee of Omdurman Islamic University reviewed and approved the proposal on 28.May.2021 after full board review (IRB name: Omdurman Islamic University Ethics Committee, Reference number: 2021/2). Approval from the Military Hospital was obtained and authorization to implement the research was granted by the administration of the ICUs. All methods were performed in accordance with the relevant guidelines and regulations of the Declarations of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Participants were informed about the research objectives and signed written informed consent was obtained from each participant prior to data collection. They were assured about their confidentiality through the use of an anonymous research tool and that the data collected from each of them were not to be used for any purposes other than those assigned to the research. Participants were free to accept or reject participation in this study.\n\n\nAvailability of supporting data\n\nAll supporting data are available.\n\n\nAuthors’ contributions\n\nSheema Hamid Seidna Hamid: Conceptualization, Data curation, Methodology.\n\nGhada Omer Hamad Abd El-Raheem: Conceptualization, Software, Formal analysis, and writing-original Draft Preparation.\n\nHana Eltayeb Salih Elamin: Validation, Writing-Review and Editing.\n\nMudawi Mohammed Ahmed Abdallah: Project adminstration, Resources.",
"appendix": "Data availability\n\nFigshare: Delirium current practice among Intensive Care Units Doctors, Khartoum- Underlying data; https://doi.org/10.6084/m9.figshare.24938505.v1. 28\n\nData are available under the terms of the Creative Commons Attribution International license (CC BY 4.0).\n\nPreprint available at: https://www.researchsquare.com/article/rs-1070778/v3.pdf\n\nDOI: https://doi.org/10.21203/rs.3.rs-1070778/v3\n\nMethods section had provided sufficient details of the materials and methods used so that the work can be repeated by others. The section was developed based on STROBE checklist of cross-sectional studies (https://www.equator-network.org/reporting-guidelines/strobe/).\n\n\nAcknowledgements\n\nThe authors are grateful to Shurouq O. H. Abdelraheem, Faculty of Engineering, University of Khartoum, for her assistance with the data-entry process. The authors also acknowledge the cooperation of the departments of Military Hospitals during data collection.\n\n\nReferences\n\nWassenaar A, van den Boogaard M , van Achterberg T , et al.: Multinational development and validation of an early prediction model for delirium in ICU patients. Intensive Care Med. 2015 Jun; 41(6): 1048–56. Epub 2015 Apr 18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan den Boogaard M , Peters SA, van der Hoeven JG , et al.The impact of delirium on the prediction of in-hospital mortality in intensive care patients. Crit. Care. 2010; 14(4): R146. Epub 2010 Aug 3. Publisher Full Text | PubMed Abstract | Free Full Text\n\nRowley-Conwy G: Barriers to delirium assessment in the intensive care unit: A literature review. Intensive Crit. Care Nurs. 2018 Feb; 44: 99–104. Epub 2017 Oct 17. PubMed Abstract | Publisher Full Text\n\nSwan JT, Fitousis K, Hall JB, et al.: Antipsychotic use and diagnosis of delirium in the intensive care unit. Crit. Care. 2012 May 16; 16(3): R84. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPisani MA, Araujo KL, Van Ness PH, et al.: A research algorithm to improve detection of delirium in the intensive care unit. Crit. Care. 2006; 10(4): R121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nColantuoni E, Koneru M, Akhlaghi N, et al.: Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review. Trials. 2021 May 20; 22(1): 354. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWassenaar A, Schoonhoven L, Devlin JW, et al.: Delirium prediction in the intensive care unit: comparison of two delirium prediction models. Crit. Care. 2018 May 5; 22(1): 114. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrown KN, Soo A, Faris P, et al.: Association between delirium in the intensive care unit and subsequent neuropsychiatric disorders. Crit. Care. 2020 Jul 31; 24(1): 476. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan, et al.: Pharmacological Management of Delirium in the ICU: A Randomized Pragmatic Clinical Trial. J. Am. Geriatr. Soc. 2019 May; 67(5): 1057–1065. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWintermann GB, Weidner K, Strauss B, et al.: Single assessment of delirium severity during postacute intensive care of chronically critically ill patients and its associated factors: post hoc analysis of a prospective cohort study in Germany. BMJ Open. 2020; 10(10): e035733. Published 2020 Oct 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang S, Han Y, Xiao Q, et al.: Effectiveness of Bundle Interventions on ICU Delirium: A Meta-Analysis. Crit. Care Med. 2021 Feb 1; 49(2): 335–346. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDeemer K, Zjadewicz K, Fiest K, et al.: Effect of early cognitive interventions on delirium in critically ill patients: a systematic review. Can. J. Anaesth. 2020 Aug; 67(8): 1016–1034. Epub 2020 Apr 24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRosgen BK, Krewulak KD, Stelfox HT, et al.: The association of delirium severity with patient and health system outcomes in hospitalised patients: a systematic review. Age Ageing. 2020 Jul 1; 49(4): 549–557. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBastos AS, Beccaria LM, Silva DC, et al.: Identification of delirium and subsyndromal delirium in intensive care patients. Rev. Bras. Enferm. 2019; 72(2): 463–467. PubMed Abstract | Publisher Full Text\n\nShafiekhani M, Mirjalili M, Vazin APsychotropic drug therapy in patients in the intensive care unit - usage, adverse effects, and drug interactions: a review. Ther. Clin. Risk Manag. 2018; 14: 1799–1812. Published 2018 Sep 28. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPage VJ, Navarange S, Gama S, et al.: Routine delirium monitoring in a UK critical care unit. Crit. Care. 2009; 13(1): R16. Epub 2009 Feb 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmit L, Dijkstra-Kersten SMA, Zaal IJ, et al.: Haloperidol, clonidine and resolution of delirium in critically ill patients: a prospective cohort study. Intensive Care Med. 2021 Mar; 47(3): 316–324. Epub 2021 Feb 16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDepetris N, Raineri S, Pantet O, et al.: Management of Pain, Anxiety, Agitation and Delirium in Burn patients: A survey of clinical practice and a review of the current literature. Annals of Burns and Fire. Disasters. June 2018; XXXI(2).\n\nGusmao-Flores D, Salluh JI, Chalhub RÁ, et al.: The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit. Care. 2012 Jul 3; 16(4): R115. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatel MB, Bednarik J, Lee P, et al.: Delirium Monitoring in Neurocritically Ill Patients: A Systematic Review. Crit. Care Med. 2018 Nov; 46(11): 1832–1841. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZimmerman LH: Practice administration and development: Protocol development and quality improvement.Bass S, Benken ST, et al., editors. Critical Care Pharmacy Preparatory Review and Recertification Course. Lenexa, KS: American College of Clinical Pharmacy; 2019 ed.2019; pp. 247–282.\n\nWang J, Peng ZY, Zhou WH, et al.: A National Multicenter Survey on Management of Pain, Agitation, and Delirium in Intensive Care Units in China. Chin. Med. J. 2017; 130: 1182–1188. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStollings JL, Gill KV: Management of Pain, Agitation, Delirium, and Neuromuscular Blockade in Adult Intensive Care Unit Patients.Bass S, Benken ST, et al., editors. Critical Care Pharmacy Preparatory Review and Recertification Course. Lenexa, KS: American College of Clinical Pharmacy; 2019 ed.2019; pp. 247–282.\n\nSun T, Sun Y, Huang X, et al.: Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case-control study. J. Int. Med. Res. 2021 Mar; 49(3): 300060521990502. PubMed Abstract | Publisher Full Text | Free Full Text\n\nÜrkmez S, Erdoğan E, Utku T, et al.: Sedation Practices and Preferences of Turkish Intensive Care Physicians: A National Survey. Turk J Anaesthesiol Reanim. 2019; 47(3): 220–227. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarbateskovic M, et al.: Pharmacological interventions for prevention and management of delirium in intensive care patients: a systematic overview of reviews and meta-analyses. BMJ Open. 2019; 9: e024562. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaramchandani, et al.: Gender differences in the use of atypical antipsychotic medications for ICU delirium. Crit. Care. 2018; 22: 220. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHamid S, Abd El-Raheem G, Elamin H, et al.: Delirium current practice among Intensive Care Units Doctors, Khartoum - Underlying data. figshare. [Dataset]. 2024. Publisher Full Text"
}
|
[
{
"id": "295363",
"date": "29 Jul 2024",
"name": "Richard E Kennedy",
"expertise": [
"Reviewer Expertise Delirium phenomenology",
"diagnosis",
"and clinical trials"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript reports on the barriers and gaps in knowledge about delirium among a sample of ICU physicians in Sudan. A random selection of providers were queried regarding their knowledge and practice in management of delirium, which were summarized and related to provider characteristics. The authors found that formal assessment of delirium was uncommon. Nonpharmacological management was commonly used, but pharmacological management was also frequent.\nThe topic is potentially an important one, as difficulties recognizing delirium are common across a number of settings, and are associated with a number of adverse patient and healthcare system outcomes. However, the methods are often not specified in sufficient detail, and the contribution of this particular study to the existing literature is not well delineated.\nThe background is generally well done, but a bit disorganized in a few spots. In particular, the statement \"Furthermore, delirium is associated with long-term cognitive impairments.\" seems out of placer from the rest of the material in the paragraph, and would be better placed with other material about adverse consequences. Similarly, the statement \"From another perspective, patients with delirium are more likely to bear increased healthcare costs than those without delirium.\" could be combined with material about adverse consequences rather than a separate paragraph. Reference 18 is for burn patients and it is not clear that these findings are applicable to the ICU setting. And noting that the mixed form of delirium is actually the most common would be helpful.\nMost importantly, the background does not clearly lay out the case for the current study. There have been multiple publications in the literature noting that delirium is often missed by clinicians, that assessment is often not performed, and many clinicians lack sufficient understanding of delirium. Given these previous studies, why is this study needed? Are there particular aspects of practice in Sudan that are different from previous studies? If so, this should be more clearly delineated to show the importance of this investigation.\nSeveral aspects of the methods are not sufficiently described. The setting notes several different types of ICUs being studied but these are not delineated. The stratified random sampling needs to be described more fully. The questionnaire used for assessing knowledge and practice is not well described - was this a standard questionnaire (in which case it should be referenced)? Or a questionnaire developed by the investigators (in which case the questions should be provided in detail, along with the validation of the questionnaire for adequately assessing the outcomes of interest)? Why were the predictor variables selected, and are these 4 sufficient for describing the associations in the sample? Is the chosen sample size formula appropriate for a series of chi-square tests?\n\nThe results are generally straightforward. However, in the description of the sample, did all of the randomized participants complete the questionnaire? Or were there refusals? A description of the flow of participants (or a flow diagram, if it is complicated) would be helpful. In addition, the sample was overwhelmingly young, inexperienced, and female. Is this typical of ICU doctors in Sudan? Or were there biases in the sample?\nWhen an ICU doctor determined delirium based on \"signs and symptoms\", does this mean that DSM-5 (or a comparable system) was used? Or does this mean an informal assessment with no specific criteria?\nSimilarly, what does \"communication with the patient to prevent confusion\" mean? Does this mean established protocols such as frequent reorientation, or is this an informal communication without a specific protocol? Such information is helpful in being able to understand and replicate the study findings.\nIt would be helpful to present odds ratios from the chi-square tests to indicate the direction of the associations, rather than just p values.\nThe discussion would benefit from more depth. There is a rather extensive literature on the recognition of delirium by physicians, the barriers to recognition, and attitudes towards management. However, the discussion only references a few studies (often a comparison to just 1 other study) rather than providing an overview of previous findings. Furthermore, the authors often only compare their results to a previous study, but do not place this in context - what does it mean if their results are similar or different from previous studies? Does this have implications for the recognition and management of delirium generally, or does this show specific aspects of management of delirium in Sudanese hospitals?\nUnder limitations, the authors should not just note the limitations, but also how these impact the study - do these affect the reliability or generalizability of the findings? Also under limitations, is the military hospital setting a limitation? Are the patient characteristics for military hospitals significantly different from the patient characteristics in non-military hospitals in Sudan, the way that there are differences in other countries?\nOverall, I think that this manuscript has the potential to make a contribution to the literature, particularly since delirium and other cognitive disorders are not well studied in settings outside of a few developed countries. However, more details are needed in several places to fully understand the study, be able to replicate their processes, and place the findings in context.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12541",
"date": "31 Oct 2024",
"name": "Ghada Abd El-Raheem",
"role": "Author Response",
"response": "Dear reviewer Richard Kennedy, Thank you for your valuable time and comments. We revised all your comments and fulfilled them. The introduction was corrected and rephrased and ref. describing burn patients is changed. As well as, the aim was well described. The methods section is detailed to be more reproducible. the details of the sampling process and the questionnaire are all detailed and provided reference for the questions asked. Also differences in the study population between military and civilian hospitals was detailed. Types of patients in military hospitals were described. Risk estimate analysis can not be computed, they are only computed for 2x2 tables without empty cells. Discussion was rewritten to be more in depth and showing all the aspects of delirium management among Sudanese doctors. Limitations were adjusted to detail the impact of limitations on the reliability and generalizability."
}
]
}
] | 1
|
https://f1000research.com/articles/13-456
|
https://f1000research.com/articles/13-1401/v1
|
21 Nov 24
|
{
"type": "Research Article",
"title": "Understanding decision making for the use of atraumatic restorative approach based on non-clinical factors by Indian pedodontists - a conjoint analysis.",
"authors": [
"Bhuvaneshwari Nadar",
"Usha GV",
"Sultan Almalki",
"Inderjit Gowdar",
"Usha GV",
"Sultan Almalki",
"Inderjit Gowdar"
],
"abstract": "Background Atraumatic Restorative Treatment (ART) approach is considered as one of the minimally invasive interventions. The success of restoration depends on various clinical factors like material, patient and operator factor. Conjoint analysis is a technique for measuring individual’s preference structures via systematical variations of products attributes in an experimental design.\n\nAim Assess Pedodontists’ perception of non-clinical factors and investigate influence of child’s age, level of cooperation and vulnerability status on their decisions to perform Atraumatic Restorative Approach (ART) approach using hypothetical patient scenario’s and conjoint design.\n\nMaterials and methods A cross-sectional exploratory survey using a web-based questionnaire was performed among Pedodontists registered as life members under Indian Association of Pedodontic and Preventive Dentistry. Self-designed structured scenario-based questionnaire was prepared and validated. Three non-clinical factors Age of child, Cooperation level and Vulnerability status were considered. Using orthogonal design, SPSS software nine profiles were created randomly along with two holdouts. Final study proforma consisted of three sections with description of eleven clinical scenarios. It was administered to participants using Google forms. Using SPSS conjoint software relative utilities for each factor on decision for using ART was estimated.\n\nResults Four hundred and thirty-two pedodontists had completed the survey (35.9%). Pedodontists considered vulnerability status of the child as the most important factor for their decision to use ART treatment. For the vulnerability status, the factor vulnerable had the greatest utility (-0.364) compared to non-vulnerable factor (0.364). For cooperation level, factor uncooperative had greater utility (-0.343), as compared to moderately cooperative (0.066) and uncooperative (0.277). For the age factor, the age of 4 years had the greatest utility (-0.175) compared with age 6 (-0.013) and age 12 (0.19).\n\nConclusion The most preferred scenario by pedodontists to consider ART as treatment of choice was child belonging to vulnerable section, being very young and uncooperative.",
"keywords": [
"atraumatic restorative treatment",
"conjoint analysis",
"dillmans technique",
"response rate",
"decision making"
],
"content": "Introduction\n\nMinimum intervention dentistry can be defined as a philosophy of professional care concerned with the first occurrence, earliest detection and possible cure of diseases on micro levels, followed by minimally invasive and patient friendly treatment to repair irreversible damage caused by such disease.1 Atraumatic Restorative Treatment (ART) is a key technique in this approach, has gained significant interest recently, especially in addressing dental care access challenges.2 Originally developed for use in developing countries with limited resources, ART has proven effective in treating primary dentition, achieving high success rates.3 Its adoption in developed countries has primarily focused on managing severe early childhood caries. ART utilizes fluoride-releasing glass ionomer materials, which help control caries progression while providing a patient-friendly, minimally invasive approach. This method not only facilitates care in resource-limited settings but also supports preventive strategies in more affluent areas, highlighting its versatility and effectiveness in managing progressive dental caries.4\n\nA meta-analysis conducted in 2021 evaluated the success rates of Atraumatic Restorative Treatment (ART) in both primary and permanent dentitions. The findings indicated impressive success rates at the 12-month follow-up mark: 71% for ART restorations on primary teeth and 96% for those on permanent teeth, without influenced by setting. These results underscore ART’s effectiveness as a reliable treatment option, reinforcing its role in minimally invasive dentistry, especially for managing caries in diverse patient populations.5\n\nThe success of dental restorations, including Atraumatic Restorative treatment (ART) is influenced by a variety of clinical factors. Among these, the operator’s decisions are crucial. Key operator factors include the diagnostic methods used, the dentist’s preferences and beliefs about restoration longevity and effectiveness, as well as their skills and experience.6 The choice of materials and the nature of the intervention also play significant roles. For example, a dentist’s restorative decisions may depend on the patient’s age, behavioral compliance, caries risk, and socioeconomic background.7 These factors shape how the dentist approaches treatment, ultimately impacting the overall success of the restoration. Therefore, a comprehensive understanding of both clinical and patient-specific variables is essential for optimizing treatment outcomes in dentistry.8\n\nOne of the most common methods for assessing dental restorative treatment decisions is through survey research. In these surveys, respondents answer direct questions about their preferences and the importance of various factors that influencing their choices of dental procedures. However, this method typically evaluates individual factors in isolation and does not capture the complexity of “derived decisions,” which consider multiple factors simultaneously.9 This limitation can affect the validity of the data and insights derived from such surveys, making it essential to consider alternative methods or complementary approaches to gain a more comprehensive understanding of decision-making in dental restorative treatments.10\n\nIn the early 1970s, Green and Rao introduced conjoint measurement to marketing research to better understand and predict buyer behavior.11 The term “conjoint” reflects the concept that multiple factors can be evaluated together,12 allowing individuals to make choices among different hypothetical products or treatment scenarios rather than assessing each characteristic in isolation. Recently, the popularity of conjoint analysis has grown in health outcomes research.13 Conjoint analysis has seen limited application in dental research, but its potential is being recognized.9,10,14,15 One notable study utilized conjoint analysis to evaluate dentists’ decisions regarding implant treatment based on various patient characteristics.10 This research revealed differences between dentists’ stated preferences and their derived decisions, suggesting that conjoint analysis can more accurately reflect actual decision-making processes by requiring respondents to make trade-offs in a choice context.\n\nDespite its advantages, studies examining dentists’ use of specific techniques and the factors influencing their decisions remain relatively scarce. As the field continues to evolve, applying conjoint analysis could provide deeper insights into how various attributes impact treatment decisions, ultimately leading to more informed and patient-centered care in dentistry.\n\nDentist’s clinical decision making regarding restorative interventions for the treatment of caries vary significantly.16 The ART approach, has been recognized as an economical and effective method for managing carious lesions, in vulnerable population.17 Decisions to use ART often depend on social and environmental factors, including a child’s age, socioeconomic status, and level of cooperation.18\n\nDespite ART’s relevance, there has been no research assessing the perceptions of Indian pedodontists. This study aims to explore how these non-clinical factors influence pedodontists’ willingness to adopt the ART approach, using hypothetical patient scenarios and a conjoint design. The central research question investigates whether differences exist in clinical decision-making among pedodontists regarding ART while considering these non-clinical factors?\n\n\nMethods\n\nThe study was designed, analyzed, and interpreted according to the Conjoint Analysis applications in the health checklist.19\n\nA cross-sectional exploratory survey was conducted among pedodontists using a web-based questionnaire. All the Pedodontists registered as life members under the Indian Association of Pedodontic and Preventive Dentistry and who were willing to participate were included.\n\nThe first stage in the design of a conjoint study is to choose attributes and assign levels.\n\n1. Defining attributes\n\nAn attribute is a characteristic of a product (e.g., color), made up of various levels (there must be at least two for each attribute) or degrees of that characteristic (e.g., red, yellow, blue).20 Conjoint analysis elicits preferences for a decision over the range of attributes and levels that define the hypothetical scenarios was used in questions. The three non-clinical factors or attributes selected for the present study were patient age, level of cooperation, and vulnerability status. These were selected based on a literature review and expert opinions. These attributes were refined through consultations with experts from the Department of Pedodontics and Public Health Dentistry. The modified attributes chosen were found to be meaningful to test and relevant to understand their interplay for clinical decisions by dentists.\n\n2. Assigning levels\n\nFor the chosen attributes, levels were assigned, providing a realistic profile/scenario capable of being traded.14 Attribute levels were identified after a literature review and discussion with experts. For age four, six and 12 years, which coincide with the three important stages, that is, primary, mixed dentition, and 12 years, the global indicator age group was selected. For the child cooperation level, Frankl’s behavior rating scale, the first and second categories (definitively negative and negative) were clubbed together and considered as uncooperative; the third category positive was modified as moderately cooperative and the fourth category definitively positive was modified as cooperative for convenience. The third factor, vulnerability status, was classified as vulnerable or non-vulnerable. Children who attended public schools, orphans, or were either physically or mentally challenged were considered vulnerable. Attending private schools, physically and mentally healthy, and living with parents as non-vulnerable.\n\nConsidering the three non-clinical factors, the possible permutation combination of the scenarios/profiles was 18. According to literature, all the Profiles should be included in the study, but by doing so it can cause fatigue and boredom set in.14 Therefore, by using Fractional Factorial Design the number of paired comparisons were reduced to the smallest number necessary for efficient estimation of utility weights.21 Using orthogonal design in SPSS software, half fraction (nine Profiles) were created randomly. The software algorithm was programmed to extrapolate the total utility values for all possible patient scenarios for each study participant, although a subset of scenarios was used.\n\nThe self-designed structured web-based questionnaire had three sections: a) nine conjoint questions, with the definition of ART, and a detailed explanation regarding the clinical presentation of the carious lesion in all scenarios. Clinical conditions were fixed for all scenarios with carious lesions involving the primary or permanent molar, with the depth of the lesion within dentin and no pulpal involvement clinically or radiographically. A description regarding the three non-clinical factors that varied in all scenarios are described. Pedodontists were requested to rate how likely they were to use ART on a 5 – point likert scale, ranging from 5 (very unlikely to use ART) to 1 (very likely to use ART). b) Two questions focused on whether pedodontists consider ART to be definitive or interim treatment and why, as well as a question asking where they learned about ART. c) The last three questions on demographic and practice characteristics. The questionnaire was pretested for content validity by two faculty members, each from the Department of Public Health Dentistry and the Department of Pedodontics. The CVI score is 0.88, suggesting good content validity.22\n\nA web-based survey questionnaire with the help of Google Forms was administered to all pedodontists registered as life members. The questionnaire was in the form of a booklet with multiple sections containing the covering letter, its usefulness and importance of the respondent response, online consent form, the survey questions, and the thank you note with participants’ suggestions regarding the study and their opinions. An invitation email was sent to all participants to 2-3 days prior to the actual email of the survey. Personalized emails that included a link to the web survey. Three reminder mails were sent after the first, fourth, and seventh week to improve the response rate. The remaining mails included a covering letter and a replacement questionnaire, emphasizing the respondent’s importance and explanation of the identification number and how confidentiality is protected and a thank you message.23\n\nSPSS conjoint software [IBM Corp. in Armonk, NY] (https://www.ibm.com/spss) was used to estimate the relative weights (utilities) for each level of the presented factors in the decision to use ART. Linear regression was used to generate the utility scores for each attribute level.\n\n\nResults\n\nIn the present survey, 432 pedodontists have responded, with a response rate of 35.9% (Figure 1). They were predominantly female 62%. About 32% were into academics and private practitioners, 28% private practitioners, 30% postgraduate students, and 10% were only academics. More than half of the respondents (62%) reported ART as interim treatment and 38% as definitive for the given scenarios. Factors included depth of lesion (53%), caries risk (24%), personal skill (4%), time constraints (5%), number of surfaces, and other reasons (7%) (see Figure 2). Pedodontists reported, they had learned ART during undergraduate courses (45.3%), postgraduation (24.7%), textbooks and articles (23.3%), and continuing dental education programs and conferences (6.7%).\n\nThe utility value for each attribute and level was computed. For the attribute cooperation, vulnerability status and age, levels uncooperative, being vulnerable, and four years had the lowest utility values of-0.242, -0.148, and -0.117, respectively (Figure 3). As a score of one was given for option very likely and five for option very unlikely, the attribute levels with the least value suggest the ones with a high preference for treatment decision. The total utility for different combinations of attribute levels is calculated using an additive linear regression equation ( Table 1). The scenario being uncooperative, belonging to vulnerable section and four years of age was most preferred for ART (2.292). Being moderately cooperative, non-vulnerable, and 12 years old was the least preferred scenario (3.114).\n\n\nDiscussion\n\nTo our knowledge, this is the first study in India to use a clinical scenario-based and rigorous statistical approach to measure pedodontists’ perception (relative utilities) for decision making for ART. We found that pedodontists value behavior and vulnerability status in decision-making when compared to the age of the child. An uncooperative child belonging to the vulnerable population and being young was the most preferred scenario in clinical decision-making for ART by Pedodontists. The depth of the lesion and individual caries risk were the most important factors reported while considering ART as a definitive treatment.\n\nThe use of conjoint design demonstrated the importance of patient factor vulnerability status in clinical restorative treatment decisions for children, in addition to their age and cooperation level. Using conjoint analysis, the relative importance of different factors, trade-offs pedodontists make between these factors, and utility or importance for combinations of test factors were possible. This is because it enables the measurement of psychological, real, or hidden factors in professional behavior (decision-making).24\n\nIn the present study, ART was considered an interim treatment by 62% pedodontists for the presented scenarios, similar finding was observed in a previous study where 82% American pedodontists stated the same.10 The views are opposing to that of the current literature wherein ART is viewed globally as a definitive treatment, particularly in certain populations that do not have access to more traditional restorative treatment.10 The World Health Organization and International Dental Federation recognize ART as part of the basic package of oral care for all communities around the world.25\n\nA pre-invitation mail and three attempts were made to contact all the registered pedodontists (1200) through online electronic mail to improve response rates, as stated by Dillman.23 We could achieve a response rate of 35.9%. With a reported average response rate of 24.8% for email surveys26 we achieved a better response. Similar response rates were found in other published surveys by Janakiram C (30.9%) and Kaul R (38.3%).27,28 Despite having active email accounts, online surveys were not acceptable to many.27 In our study about 432 pedodontists participated. Al-Omari B et al20 recommended a sample size of 300 for conjoint study. Therefore, the study sample size was larger than the recommended sample size for the conjoint analysis.\n\nControlled clinical factors independently drive the decision to administer ART. It enabled assessment of the pedodontists’ perception and their relative importance on the other three non-clinical factors in clinical decision-making. The clinical presentation was fixed in accordance with recent evidence showing that ART single-surface restorations using high-viscosity GIC had a high survival rate in both primary and permanent teeth, comparable to that of traditional amalgam restorations.29 Moreover, as ART restorations are both minimally invasive and caries-protective when compared to other traditional restorative methods, it can be considered as a treatment of choice for single-surface caries lesions.30\n\nIn the present study, ART was more likely to be preferred by young children who were uncooperative and vulnerable. These findings are consistent with the endorsement of the World Health Organization and the International Association for Dental Research. According to the WHO, ART may be used to restore and prevent caries in young patients, uncooperative patients, or patients with special health care needs31 and also where traditional cavity preparation and/or placement of traditional dental restorations are not feasible.31 As stated by Jo E Frenken, ART is the best treatment for very young children with behavioral problems.32 The results are in accordance with the study by Kateeb et al., where the pediatric dentist preferred ART for uncooperative children.10 Interestingly, in the present study, young age had less utility value and the last preferred factor among the three non-clinical factors. In contrast, young age was the second most preferred factor for ART treatment in a study by Kateeb et al.10\n\nThe vulnerability status factor was considered to identify the relative importance of pedodontists in clinical decision-making. The results showed that the vulnerability status of the child was the second most important factor stated by study participants. Even though Atraumatic Restorative Treatment (ART) is considered an economical and effective method for preventing and controlling carious lesion development in vulnerable populations.18,33 The recent evidence stated higher survival rates comparable to traditional restorations and being safe to use.33 ART can be considered to be a cornerstone of minimal intervention caries management in combination with prevention and minimal invasion.30 Therefore, thorough and careful performance of all the technical steps can lead to successful long-lasting restorations. Further studies on atraumatic restorative treatment are needed to validate its effectiveness and acceptability.\n\nA study by Molina et al. showed a higher one-year survival rate for all ART restorations compared to conventional restorations in adults with intellectual disability.34 The strengths of the study were the joint design, which allowed an unbiased precise preference estimate, thereby reducing confounding bias. Anonymous mailed questionnaires reduced interviewer bias and social desirability bias. The survey had a few scenarios and questions, thereby reducing response fatigue. A subset of potential patient scenarios was randomly selected and presented to participants using an orthogonal fractional factorial design. The software algorithm was programmed to extrapolate the total utility values for all possible patient scenarios for each participant. It generates a random sequence of scenarios, avoiding learning and primacy biases.\n\nThe hypothetical nature of questions, time consumption, and reported behavior may not be the actual behavior, which were the limitations of the study. Further studies are required to confirm the hypotheses derived from this study. Dental professionals should be encouraged to adopt new, less invasive, and simple restorative techniques, such as ART. Pedodontists can be sensitized to the effectiveness of ART, irrespective of children’s cooperation, vulnerability status, and age. This can be emphasized by incorporation into the early stages of clinical training through CDE and CME programs.\n\n\nConclusion\n\nThe most preferred scenario by pedodontists to consider ART as the treatment of choice was an uncooperative child belonging to a vulnerable section and being very young.\n\n\nEthics and consent\n\nThe study protocol was approved by the Institutional Review Board of Bapuji Dental College and Hospital, under approval number BDC/383/2017-18 dated 24/11/2017. The Committee on Research Ethics adhered to international guidelines for human subject protection, including the Declaration of Helsinki, The Belmont Report, and CIOMS guidelines. All participants provided voluntary written informed consent using an electronic consent system before accessing the online survey. The consent form clearly outlined the survey’s purpose, the estimated time required to complete the questionnaire, and used simple, understandable language. Participants were informed that they could withdraw from the survey at any time, and that their personal information would be kept confidential.",
"appendix": "Data availability statement\n\nFigshare – Understanding decision making for use of Atraumatic Restorative Approach based on non-clinical factors by Indian Pedodontists - A conjoint analysis, https://doi.org/10.6084/m9.figshare.27188796.35\n\nThis project contains following underlying data:\n\n• Conjoint study-data.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).35\n\nFigshare - Understanding decision making for the use of atraumatic restorative approach based on non-clinical factors by Indian pedodontists - a conjoint analysis (Questionnaire), https://doi.org/10.6084/m9.figshare.27283890.36\n\nThis project contains following extended data\n\n• Survey questionnaire, participant information and consent form.docx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).\n\n\nReferences\n\nTyas MJ, Anusavice KJ, Frencken JE, et al.: Minimal intervention dentistry--a review. FDI Commission Project 1-97. Int. Dent. J. 2000 Feb; 50(1): 1–12. PubMed Abstract | Publisher Full Text\n\nSaber AM, El-Housseiny AA, Alamoudi NM: Atraumatic Restorative Treatment and Interim Therapeutic Restoration: A Review of the Literature. Dent. J (Basel). 2019 Mar 7; 7(1): 28. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHonkala E, Behbehani J, Ibricevic H, et al.: The atraumatic restorative treatment (ART) approach to restoring primary teeth in a standard dental clinic. Int. J. Paediatr. Dent. 2003 May; 13(3): 172–179. PubMed Abstract | Publisher Full Text\n\nSmales RJ, Yip HK: The atraumatic restorative treatment (ART) approach for primary teeth: review of literature. Pediatr. Dent. 2000 Jul-Aug; 22(4): 294–298. PubMed Abstract\n\nGarbim JR, Laux CM, Tedesco TK, et al.: Atraumatic restorative treatment restorations performed in different settings: systematic review and meta-analysis. Aust. Dent. J. 2021 Dec; 66(4): 430–443. PubMed Abstract | Publisher Full Text\n\nJiang M, Fan Y, Yan Li K, et al.: Factors affecting success rate of atraumatic restorative treatment (ART) restorations in children: A systematic review and meta-analysis.J. Dent.2021; 104: 103526. PubMed Abstract | Publisher Full Text\n\nMickenautsch S, Grossman E: Atraumatic Restorative Treatment (ART): factors affecting success. J. Appl. Oral Sci. 2006; 14: 34–36. PubMed Abstract | Publisher Full Text\n\nBader J, Shugars D: What do we know about how dentists make caries-related treatment decisions? Community Dent. Oral Epidemiol. 1997 Feb; 25(1): 97–103. PubMed Abstract | Publisher Full Text\n\nBader JD, Shugars DA: Understanding dentists’ restorative treatment decisions. J. Public Health Dent. 1992 Winter; 52(2): 102–110. PubMed Abstract | Publisher Full Text\n\nKateeb ET, Warren J, Gaeth G, et al.: The willingness of US pediatric dentists to use atraumatic restorative treatment (ART) with their patients: a conjoint analysis. J. Public Health Dent. 2014 Summer; 74(3): 234–40. Epub 2014 Mar 17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoele P, Hoogstraten J: Determinants of dentists’ decisions to initiate dental implant treatment: a judgment analysis. J. Prosthet. Dent. 1999 Apr; 81(4): 476–480. PubMed Abstract | Publisher Full Text\n\nGreen PE, Rao VR: Conjoint Measurement for Quantifying Judgmental Data. J. Mark. Res. 1971; 8: 355. Publisher Full Text\n\nJohnson RM: Trade-Off Analysis of Consumer Values. J. Mark. Res. 1974; 11: 121–127. Publisher Full Text\n\nRyan M, Farrar S: Using conjoint analysis to elicit preferences for health care. BMJ. 2000 Jun 3; 320(7248): 1530–1533. PubMed Abstract | PubMed Abstract | Free Full Text\n\nChakraborty G, Gaeth GJ, Cunningham M: Understanding consumers’ preferences for dental service. J. Health Care Mark. 1993 Fall; 13(3): 48–58. PubMed Abstract\n\nCunningham MA, Gaeth GJ, Juang C, et al.: Using choice-based conjoint to determine the relative importance of dental benefit plan attributes. J. Dent. Educ. 1999 May; 63(5): 391–399. PubMed Abstract | Publisher Full Text\n\nJobim Jardim J, Henz S, Barbachan E, et al.: Restorative Treatment Decisions in Posterior Teeth: A Systematic Review. Oral Health Prev. Dent. 2017; 15(2): 107–115. PubMed Abstract | Publisher Full Text\n\nFrencken JE, Leal SC: The correct use of the ART approach. J. Appl. Oral Sci. 2010 Jan-Feb; 18(1): 1–4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBridges JFP, Hauber AB, Marshall D, et al.: Conjoint analysis applications in health--a checklist: a report of the ISPOR Good research practices for Conjoint analysis task force. Value Health. 2011 Jun; 14(4): 403–413. PubMed Abstract | Publisher Full Text\n\nAl-Omari B, Farhat J, Ershaid M: Conjoint Analysis: A Research Method to Study Patients’ Preferences and Personalize Care. J. Pers. Med. 2022 Feb 13; 12(2): 274. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPhillips KA, Maddala T, Johnson FR: Measuring preferences for health care interventions using conjoint analysis: an application to HIV testing. Health Serv. Res. 2002; 37: 1681–1705. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYaghmaie F: Content validity and its estimation. J. Med. Educ. 2003; 3(1): e105015. Publisher Full Text\n\nHoddinott SN, Bass MJ: The dillman total design survey method. Can. Fam. Physician. 1986 Nov; 32: 2366–2368. PubMed Abstract | Free Full Text\n\nLuce RD, Tukey JW: Simultaneous conjoint measurement: A new type of fundamental measurement. J. Math. Psychol. 1964; 1: 1–27. Publisher Full Text\n\nHelderman W, Benzian H: Implementation of a Basic Package of Oral Care: towards a reorientation of dental NGOs and their volunteers. Int. Dent. J. 2006 Feb; 56(1): 44–48. PubMed Abstract | Publisher Full Text\n\nMuñoz-Leiva F, Sánchez-Fernández J, Montoro-Ríos F, et al.: Improving the response rate and quality in Web-based surveys through the personalization and frequency of reminder mailings. Qual. Quant. 2010; 44: 1037–1052. Publisher Full Text\n\nJanakiram C, Joseph J, Antony B: Career Satisfaction Among Dental Public Health Specialists in India - A Cross-sectional Survey. J. Clin. Diagn. Res. 2017 Jan; 11(1): ZC97–ZC101. Epub 2017 Jan 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaul R, Angrish P, Jain P, et al.: A Survey on the Use of Antibiotics among the Dentists of Kolkata, West Bengal, India. Int J Clin Pediatr Dent. 2018 Mar-Apr; 11(2): 122–127. Epub 2018 Apr 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMickenautsch S, Yengopal V, Banerjee A: Atraumatic restorative treatment versus amalgam restoration longevity: A systematic review. Clin. Oral Investig. 2010 Jun; 14: 233–240. PubMed Abstract | Publisher Full Text\n\nHolmgren CJ, Roux D, Doméjean S: Minimal intervention dentistry: part 5. Atraumatic restorative treatment (ART)--a minimum intervention and minimally invasive approach for the management of dental caries. Br. Dent. J. 2013 Jan; 214(1): 11–18. PubMed Abstract | Publisher Full Text\n\nPolicy on Alternative Restorative Treatment (ART).2001 [cited 10 September 2024]. Reference SourceReference Source\n\nFrencken JE, Leal SC, Navarro MF: Twenty-five-year atraumatic restorative treatment (ART) approach: a comprehensive overview. Clin. Oral Investig. 2012 Oct; 16(5): 1337–46. Epub 2012 Jul 24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLopez N, Simpser-Rafalin S, Berthold P: Atraumatic restorative treatment for prevention and treatment of caries in an underserved community. Am. J. Public Health. 2005 Aug; 95(8): 1338–9. Epub 2005 Jul 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMolina GF, Faulks D, Mazzola I, et al.: One year survival of ART and conventional restorations in patients with disability. BMC Oral Health. 2014 May 7; 14: 49. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNadar B: Understanding decision making for use of Atraumatic Restorative Approach based on non-clinical factors by Indian Pedodontists - A conjoint analysis. Dataset. figshare. 2024. Publisher Full Text\n\nNadar B: Understanding decision making for the use of atraumatic restorative approach based on non-clinical factors by Indian pedodontists - a conjoint analysis (Questionnaire). figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "343455",
"date": "02 Dec 2024",
"name": "Dr Suresh KV",
"expertise": [
"Reviewer Expertise TMDs",
"Orofacial pain",
"CBCT"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for this opportunity\n\nThe manuscript is well-structured and adheres to the STROBE guidelines, ensuring clarity and transparency in reporting. Both the title and abstract are informative, providing a concise summary of the study’s aims, methods, and key findings. The introduction effectively highlights the need for the study, clearly stating the research aim and objectives. The background provided justifies the significance of the study in the current scientific context. The authors have thoroughly explained the validation process for the data collection instrument, ensuring reliability and credibility. The study design is well-described, and the sample size has been scientifically estimated using an appropriate formula. The depth of detail in the method of data collection facilitates replication, making the research transparent and reproducible. The consent process is described in detail, ensuring adherence to ethical standards in research. The statistical methods used for analysis are clearly specified and are appropriate for the type of data obtained. This ensures the robustness of the results and provides confidence in the conclusions drawn. The results are clearly presented in well-organized tables, with comprehensive information about the characteristics of the study participants. This allows for a detailed understanding of the study's sample and its generalizability. The discussion provides a concise summary of the key results and interprets them within the context of previous literature. The authors have appropriately cited studies with similar findings, providing a balanced and informed discussion. The manuscript includes useful recommendations for conducting similar research in the future, based on the study's findings and limitations. References are following the journal’s guidelines.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "343457",
"date": "03 Dec 2024",
"name": "Dr Praveen Gangadharappa",
"expertise": [
"Reviewer Expertise IMPLANTS",
"IMPRESSIONS",
"COMPLETE DENTURE PROSTHODONTICS"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle and Abstract: The title and abstract effectively summarize the key aspects of the study, giving a clear overview of its scope and objectives. Introduction: The introduction presents a well-structured and logical framework, supported by relevant citations. It successfully establishes the background and context for the study, highlighting the need for the research in the field. Need for the Study: The rationale for the study is strongly justified, with a solid scientific background that highlights its significance. The research addresses an important gap in the existing literature, underlining the contribution it makes to the field. • Methodology: The methodology is clearly described and easily replicable. The research design, sampling methods, and procedures are well-detailed. The statistical analysis is appropriate and robust, ensuring that the findings are valid and reliable. Tables and Figures: The tables and figures are relevant and well-aligned with the objectives of the study. They help in presenting the data clearly and support the interpretation of the results. Discussion: The discussion is meaningful and provides a thorough interpretation of the results. The comparison with previous studies is appropriate and helps to contextualize the findings within the broader scientific landscape. Conclusion: The conclusion is consistent with the study's findings. It clearly summarizes the key outcomes and provides insights that are logically derived from the research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1401
|
https://f1000research.com/articles/13-1399/v1
|
21 Nov 24
|
{
"type": "Review",
"title": "Conceptual review of consumer satisfaction theories with expectation-confirmation and disconfirmation paradigm for business sustainable growth and decision making",
"authors": [
"Ganesh Ramasamy",
"Gomala Devi Ramasamy",
"Puvaneswary Ramasamy",
"Gomala Devi Ramasamy",
"Puvaneswary Ramasamy"
],
"abstract": "Consumer satisfaction is an outcome of business marketing activities, bridging the buying and usage phases with subsequent consequences such as attitude changes, recurring purchases, and brand loyalty. Most studies have utilized variations of the disconfirmation paradigm, which posits that satisfaction is influenced by the degree and type of disconfirmation experienced and initial expectations. Despite the importance of satisfaction, there remains a paucity of evidence on the cause and effect leading to expectation-confirmation and disconfirmation paradigm. This paper explores the reasons and the key factors in the perspectives of the relevant literature and aims to identify the intention of confirmation and disconfirmation in satisfaction theories. This conceptual paper also suggests various critical analyses based on the arguments for and against the paradigm in customer satisfaction. Consequently, the paper seeks to examine existing gaps in the literature regarding customer satisfaction theories for business sustainability and decision making, which may need to be more concise in the satisfaction generation process.",
"keywords": [
"sustainable growth",
"decision making",
"customer satisfaction",
"confirmation",
"disconfirmation",
"consumer behavior"
],
"content": "Introduction\n\nCustomer satisfaction has reached its lowest point in the past two decades globally, and despite efforts and investments in customer experience tools, satisfaction continues to decline (Hult & Morgeson, 2023). Customer satisfaction plays a pivotal role in influencing purchasing decisions and ensuring customer loyalty. This satisfaction is inherently subjective, shaped by emotions or thoughts, and influenced by factors such as product performance, consumer experiences, and expectations, all within specific circumstances (Giese & Cote, 2002; Yüksel & Yüksel, 2001; Rahman et al., 2017).\n\nSatisfaction is affected by the extent and direction of disconfirmation, which occurs when there is a difference between initial expectations and actual outcomes (Mittal et al., 2023; Murray, 1938; Pillai, 2021; Siu et al., 2016; Yeh et al., 2017; Ali et al., 2016; Lee & Yun, 2015; Jayasankaraprasad & Kumar, 2012; Surprenant & Churchill, 1982). Disconfirmation paradigm is central to understanding consumer satisfaction.\n\nVarious studies have shown that expectations can be positively disconfirmed when product performance exceeds expectations, resulting in satisfaction, or negatively disconfirmed when performance falls short, leading to dissatisfaction (Mittal et al., 2023; Ali et al., 2016; Lee & Yun, 2015). Positive customer satisfaction is linked to beneficial outcomes such as customer retention, positive word of mouth, increased spending, and favorable pricing. At the firm level, this translates to improved product-market performance, accounting performance, and financial-market success (Mittal et al., 2023). The expectation-confirmation and disconfirmation paradigm offers a valuable framework for analyzing consumer experience formation and evaluation (Oliver & Winer, 1987; Spreng et al., 1996).\n\nThe purpose of this research, therefore, is to find out the various causes and influential factors and deepen the understanding of the expectation-confirmation and disconfirmation paradigm as a framework for customer satisfaction. The research explores the bases of consumer expectations formation before purchasing a product or service and the consistency of consumer responses to disconfirmation, examining whether satisfaction or dissatisfaction arises when perceived performance deviates from expectations. By addressing these issues, the paper seeks to provide insights into how businesses can better align their offerings with consumer expectations, thereby enhancing customer satisfaction and loyalty.\n\nIn the assessment of satisfaction, the combined impact of expectation and perception of discrepancy can be significant, especially when the consumer needs and wants are examined in relation to the formation of a reference identity, which is then used for comparative evaluation (Vedadi et al., 2013; Oliver, 1980). Outcomes that go below expectations are typically evaluated as being below their benchmark. Nevertheless, in cases where the result surpasses expectations (positive disconfirmation), it is assessed as superior to the standard point of reference (Oliver, 1980). Quinsey (1970) defines the adaptation level as the point at which perception becomes neutral or indifferent. This occurs because the perceived magnitude of a stimulus decreases as it gets closer to the Adaptation Level. Stimuli above the Adaptation Level elicit different judgments or responses compared to stimuli below the Adaptation Level, which produce opposite results. When people encounter new stimuli, their judgments of these stimuli will typically influence their previous experiences with similar objects. The perceived difference between the new and previous stimulus will determine how satisfied individuals are with the new stimulus (Pillai, 2021; Siu et al., 2016; Yeh et al., 2017).\n\nThese have an interplay with three factors: the perception of the stimulus, context, and psychological and physiological qualities of a particular structure. Once established, the “adaptation level” will persist in an individual’s initial position to guide their subsequent evaluations, regardless of whether they are focused on any aspects (Siu et al., 2016; Yeh et al., 2017). The end assessment of an individual’s judgment will only be altered by significant impacts on the adaption level (Vedadi et al., 2013; Khalifa & Shen, 2005). In assessing satisfaction, one might use a person’s expectations regarding the performance of a product as their adaption level (Khalifa & Shen, 2005). These factors include the individual’s experience with the product and other identifying elements, promotional attributes of the sales assistant, and qualities such as persuasive power and perceptual distortion. The adaption stage can also affect the customer’s repurchase choice, which determines how much the product exceeds, meets, or falls short in any expectations (Vedadi et al., 2013; Pillai, 2021). The Adaptation Level Theory offers valuable insights into how individuals perceive stimuli and assess satisfaction, taking into account both their expectations and contextual factors.\n\nAdaptation Level Theory offers valuable insights into the dynamic nature of customer satisfaction and the importance of relative comparisons and expectation management. However, several unresolved issues, including the subjectivity of adaptation levels, measurement challenges, cultural differences, and the role of emotions and technology, necessitate further research and refinement of the theory to enhance its applicability in the modern business landscape. Addressing these issues can help businesses better understand and predict customer satisfaction in an ever-evolving market.\n\nThe theory serves as the foundation for establishing precise assertions regarding the connection between effort, expectation, and evaluation (Dahl & Dunn, 2012; Yeh et al., 2017). According to Cardozo (1965), contrast theory suggests that when a customer receives a goods that is of lower value than expected, they would carefully examine the discrepancies between the obtained goods and their expectations. The evaluation may also result in potential consumer amplification of the discrepancy (Yeh et al., 2017). In this context, emphasis on individuals’ ability to differentiate favorable or unfavorable products will have an impact on their original expectations. This can lead to a shift in their evaluation away from their expectations if their expectations are not aligned with the effort.\n\nConsumer or customer effort refers to the somatic, cognitive ability, or monetary resources that are required to acquire a specific product (Vedadi et al., 2013; Pillai, 2021) and in line with that, empirically revealed disparity while comparing ballpoint pens with catalogs featuring products of varying quality (poor or high). The respondents were presented with catalogs in order to establish both low and high expectations regarding a pen. Subsequently, the participants were assessed based on the caliber of a pen that differed from the pen depicted in the catalog. The endeavor was also influenced by an enhanced shopping experience (Cardozo, 1965). In addition, study findings corroborate the notion that individuals who invest minimal effort in obtaining a product that falls short of their expectations tend to evaluate the product less favorably compared to those who anticipated and received the same goods. Furthermore, in the treatment group, individuals who received a lower quantity than anticipated assessed the product less favorably in comparison to those who received the predicted amount. The findings of this research study align with the contrast theory, which suggests that individuals who had their expectations negatively disconfirmed rated a reward as less favorable compared to those whose expectations and outcomes were congruent (Vedadi et al., 2013; Pillai, 2021).\n\nAccording to contrast theory, when the actual performance of a product or service does not fulfill a customer’s expectations and criteria, the customer will exaggerate the difference between what they expected and what they received (Danijela et al., 2015). As a result, customers may overstate the difference when the actual performance of the product or service falls short of their expectations, which is known as negative disconfirmation. Moreover, when customers encounter negative disconfirmation, they interpret the performance as falling short of their expectations. However, there is a potential for exaggerating the disparity, leading to a perception that it is even more severe than it actually is (Danijela et al., 2015). The contrast theory illuminates how customers evaluate products by taking into account the interplay between effort, expectations, and actual performance. Furthermore, it recognizes the potential for exaggerating discrepancies in their assessments.\n\nContrast Theory provides valuable perspectives into consumers’ strong reactions when their expectations are unmet, emphasizing the importance of expectation management and accurate marketing. However, several unresolved issues, such as the degree of expectation deviation, individual and cultural differences, long-term effects, and the role of moderating variables, require further exploration. Addressing these issues can enhance the applicability of contrast theory in understanding and managing customer satisfaction in a dynamic market environment.\n\nAssimilation can be defined as the overall thoughts of activity integrating new into the existing pool of attitudes to prevent conflicting beliefs. Sherif and Hovland (1961) introduced this concept in their Social Judgment theory, stating that a person forms evaluation and may alter their attitudes when they compare new stimuli to their existing internal range. When the responses deviate from the internal range, a grid line of rejection occurs. Affirmation will happen when responses resemble the person’s inner quality. Apart from that, indifference arises when the responses are dissimilar or when a distinct difference is recognized (Sherif & Hovland, 1961).\n\nAccording to Lanktan and McKnight (2012), the assimilation contrast hypothesis suggests that assimilation occurs when the comparison falls within a specific range of acceptance. This implies that the individual will perceive the new stimulus as more closely aligned with their existing ideas than the actual reality. Consequently, this will result in the assimilation of the new information into the individual’s preexisting views. If the differentiation falls within the grid line of rejection, the opposite is bound to occur. In this case, there will be a contrast, and the individual will see the new stimuli as being more distinct from their own ideas. As a result, rejection will occur (Lanktan & McKnight, 2012).\n\nAssimilation occurs when an idea aligns with a person’s existing attitude, causing them to distort the information to make it more similar to their current beliefs. On the other hand, contrast arises when a thought differs significantly from one’s own, leading to a distorted perception of a more significant gap. However, if a message closely aligns with a person’s beliefs or opinions, it is considered to have a significant impact (Peyton et al., 2003; Kokthi & Kelemen-Erdős, 2018).\n\nNumerous studies have demonstrated that end users’ impressions of a product’s attributes tend to align with their expectations, supporting the assimilation effect. This validates the existence of specific ranges or boundaries within which consumers either accept or reject their perception of a product (Anderson, 1973). When the consumer’s expectations and actual product performance differ, they tend to associate the product with their expectations rather than performance. However, if the difference is significant and falls within the zone of rejection, the contrast effect occurs. In such cases, end users typically scrutinize the details of the disparity between the product and their expectations (Danijela et al., 2015; Peyton et al., 2003).\n\nIn a similar vein, Kokthi and Kelemen-Erdős (2018) conducted research to explore the impact of branding on customer decision-making, specifically focusing on two well-known brands: Brand A and Brand B. They employed the assimilation-contrast method to analyze how brand information influences consumer perceptions. During three specific scenarios, study participants expressed their preferences for Brand A and Brand B products. Interestingly, in a blind taste test, customers couldn’t discern a significant difference between the two products. However, in a label test, Brand B outperformed Brand A, indicating a stronger preference for the Brand B. This study suggests that brand information, often through labels, can either confirm or challenge buyers’ expectations. Notably, when customers received complete information, including brand labels, Brand A received higher preference ratings, highlighting the influence of brand information on consumer preferences. The Assimilation-Contrast Theory sheds light on the relationship between brand information and consumer perceptions, while the disconfirmation paradigm also plays a role in shaping these decisions. The theory provides insights into how brand information impacts consumer decisions. The theory has a contrasting effect on the alignment of expectations and perceptions, the role of cognitive dissonance, and the impact of marketing on managing customer expectations, which leads to the issues of complexity of defining the latitude of acceptance, the challenges in measuring expectations and perceptions, the level of consumer experiences, and the interplay with other consumer behavior theories. Additionally, the theory’s limits on emotional factors, the influence of social and digital media, and cross-cultural validity for customer satisfaction.\n\nThe cognitive dissonance theory suggests that when there is a difference between a consumer’s expectations and the actual performance of a product, the consumer will adjust their perception of the product to align with their expectations. This adjustment can involve lowering their expectations or assimilating their perception to a more general or less conflicting level (Hamza & Zakkariya, 2012; Hasan & Nasreen, 2012). Additionally, Anderson (1973) supports this claim using Festinger’s theory of cognitive dissonance. Cognitive dissonance refers to the emotional pain experienced when a product’s outcome contradicts a consumer’s existing beliefs or expectations. This can be similarly interpreted as the psychological discomfort experienced when the consumer has a different conception regarding a belief or point of view, leading to a desire for consistency or harmony (Kotler & Keller, 2009; Bose & Sarker, 2012).\n\nFurther to the above, cognitive dissonance theory posits that individuals possess both cognitive and emotional aspects, and it refers to a psychological phenomenon that occurs when there is a mismatch between an individual’s beliefs and the resulting outcomes, which challenges their beliefs (Solomon, 2020). According to the hypothesis, when a person’s thoughts or beliefs are conflicting, they will attempt to minimize the conflict, specifically by reducing the feeling of discomfort after buying a specific product (Costanzo, 2012). The presence of these conflicting features stimulates cognitive dissonance, prompting individuals to seek a state of harmony and alleviate psychological tension (Solomon, 2020; Pillai, 2021).\n\nThere are three situations that might lead to cognitive dissonance: First, encountering a logical inconsistency. Second, when a person’s prior behavior, attitudes, beliefs, and their current surroundings do not align. Third, when a person’s positive belief is proven wrong (Solomon, 2020; Pillai, 2021). Cognitive dissonance theory explains how individuals reconcile conflicting beliefs and perceptions, impacting their satisfaction and decision-making processes.\n\nCognitive Dissonance Theory explains that individuals experience psychological discomfort (dissonance) when holding contradictory beliefs or attitudes, influencing post-purchase behavior and customer satisfaction. Key arguments include post-purchase rationalization, where consumers seek positive information to justify their decisions, and the role of marketing in reinforcing satisfaction by aligning messages with consumer beliefs. Unresolved issues include challenges in measuring dissonance, understanding its evolution over time, and considering individual differences and cultural variations. Additionally, the theory’s focus on cognitive aspects overlooks emotional factors, and the impact of social media on amplifying dissonance through diverse opinions remains underexplored. Integrating these insights with other consumer behavior theories could provide a more comprehensive understanding of customer satisfaction.\n\nCustomer satisfaction is measured by comparing the purchase outcome to a benchmark known as the Comparison Level (CL). When a specific result exceeds the CL, it is referred to as a positive discrepancy event, which can be regarded as satisfactory (Solomon, 2020; Pillai, 2021; Oshikawa, 1968). Conversely, if the outcomes go below the Comparison Level, they are considered negative disparities and are seen as dissatisfying. The theory posits that the parallel resemblance is measured by averaging the main results divided by comparable interactions experienced by the consumer (Pillai, 2021; Oshikawa, 1968; Kelley & Thibaut, 1978). With these, it can be proposed that the consumer is aware of the results; however, they have yet to personally experience and encompass outcomes achieved by others who have had similar experiences. There are three main elements in considering CL: first, the outcomes that an individual has personally experienced; second, the outcomes of others who have had similar experiences; and finally, the distinctive expectations that are formed in the individual’s current interaction (Kelley & Thibaut, 1978).\n\nThe Comparison Level theory offers valuable insights into how customers assess their experiences by considering relative outcomes and expectations. It recognizes that satisfaction is contingent upon context and influenced by both individual and observed interactions. Comparison Level Theory offers a valuable framework for understanding customer satisfaction through the lens of expectations and social influences. However, unresolved issues such as measuring subjective and dynamic comparison levels, integrating with other theories, addressing cultural differences, managing the impact of digital media, and incorporating emotional factors highlight the need for further research. Addressing these gaps can enhance the theory’s applicability and provide deeper insights into consumer behavior and satisfaction (Khongorzul et al., 2022).\n\nValue Percept Disparity Theory emphasizes that contentment or dissatisfaction triggers a cognitive-evaluative process (Locke, 1967). This involves comparing an individual’s perceptions of a specific object or beliefs about an activity with their personal values—representing their needs, wants, and desires (Solomon, 2020; Kotler & Keller, 2009). It demonstrates that when an object or activity closely aligns with an individual’s values, it is positively evaluated (Westbrook & Reilly, 1983).\n\nConversely, when there is a significant disparity between the perceived value and actual worth, the evaluation becomes less favorable. This discrepancy leads to a decrease in positive emotions and an increase in negative emotions associated with the experience of discontent (Solomon, 2020; Murray, 1938). The theoretical system must satisfy three essential characteristics: the perception of product, institution, or marketplace behavior, alignment with the consumer’s value standards, and judgment regarding the relationship between the consumer’s perception and value system (Murray, 1938). In reference to this, views of products, companies, or marketplace behaviors are assessed based on the consumer’s level of value (Alkilani et al., 2013; Murray, 1938).\n\nThe perception of value plays a critical role in molding consumer behavior and affecting the choices they make when purchasing goods or services. Comprehending the perceived value is crucial for organizations to fulfill and surpass customer expectations. Perceived value is typically composed of various elements, such as functional, emotional, and social advantages (Sweeney & Soutar, 2001). Customers evaluate the entire worth of a product or service by taking into account how effectively it fulfills their practical requirements, the emotional gratification it offers, and the potential social status it may bestow.\n\nThe Value Percept Disparity Theory examines how consumers assess their happiness with a transaction by comparing their expectations before making the purchase with their experiences after making the buy. By acquiring a deep understanding of various perspectives, firms may customize their products and interactions to more closely match customer expectations, hence improving overall happiness. Gaining insight into the determinants of perceived value enables organizations to develop more efficient marketing tactics. Businesses may distinguish themselves from the competition and connect with consumers on a deeper level by emphasizing their distinctive advantages and value propositions. Resolving discrepancies between client expectations and their actual experiences can improve customer satisfaction and foster loyalty. Additionally, it can cultivate favorable word-of-mouth and advocacy, thereby enhancing the brand’s market position (Yi, 1990). The Value Percept Disparity Theory guides organizations in enhancing perceived value, addressing customer expectations, and fostering loyalty.\n\nValue Percept Disparity Theory offers valuable insights into customer satisfaction by emphasizing the importance of perceived value relative to expectations. Key arguments include the multidimensional nature of value, the impact of individual differences, and the role of marketing in shaping value perceptions. However, unresolved issues such as measuring perceived value, understanding its dynamics, addressing cultural and contextual factors, integrating with other theories, considering emotional influences and the impact of digital and social media highlights the need for further research. Addressing these gaps can enhance the theory’s applicability and provide deeper insights into consumer behavior and satisfaction.\n\nThe generalized negativity theory suggests that negative experiences or under-fulfillment of expectations substantially impact customer satisfaction more than positive experiences (Szymanski & Henard, 2001; Hayden, 2014). This theory argues that customers are more likely to remember and share negative experiences whereby these customers share their dissatisfaction with others, which can cause negative word-of-mouth and harm the company’s reputation (Tsai et al., 2014; Ferguson & Johnston, 2011). This theory posits that negative experiences or under-fulfillment of expectations have a stronger influence on customer satisfaction than positive experiences (Ferguson & Johnston, 2011; Uzir et al., 2020). Accordingly, customer satisfaction is a consumption-related fulfillment response ranging between perfect and over-fulfillment levels.\n\nTypical manifestations of customer satisfaction are pleasure, delight, contentment, and relief. Under-fulfillment of expectations is believed to cause customer dissatisfaction. The formation of customer satisfaction requires at least a minimum amount of direct experience with a product or service (Ferguson & Johnston, 2011). The expectancy/disconfirmation paradigm is commonly used to study customer satisfaction and includes four constructs: expectations, performance, disconfirmation, and satisfaction. The generalized negativity theory in customer satisfaction suggests that negative experiences or under-fulfillment of expectations have a more substantial impact on overall satisfaction than positive experiences (Uzir et al., 2020). The theory maintains that dissatisfaction is more salient and impactful than satisfaction, and customers are more likely to express their dissatisfaction and spread negative feedback (Ji & Liu, 2020; Laczniak et al., 2001). Understanding and addressing negative experiences are crucial for maintaining customer satisfaction and reputation.\n\nGeneralized negativity theory provides the effect of negative experiences on customer satisfaction. However, it is essential to address its arguments and unresolved issues to develop a more comprehensive understanding of customer satisfaction dynamics. Balancing the focus on negativity with the promotion of positive experiences, integrating insights from positive psychology, and considering contextual and individual differences can enhance the applicability and robustness of Generalized negativity theory in a rapidly evolving consumer landscape. Addressing these challenges will help create more effective strategies for managing customer satisfaction and fostering positive customer relationships.\n\nHypothesis testing theory is a statistical method used to make inferences about a population based on sample data (Hasibuan, 2020). In the context of customer satisfaction, hypothesis testing theory involves formulating research hypotheses and conducting statistical tests to determine if there is a significant relationship between variables (Duca, 2022). For instance, in the case of customer satisfaction, the null hypothesis (Ho) could be that there is no relationship between the level of customer satisfaction and buying behavior, while the alternative hypothesis (H1) could be that there is a significant relationship. Data on customer satisfaction levels and buying behavior will be collected to test this hypothesis and subsequently be analyzed using appropriate statistical tests, such as regression analysis, to determine if there is evidence to support or reject the null hypothesis.\n\nThe importance of hypothesis testing theory in customer satisfaction lies in its ability to provide empirical evidence and support for any insights or claims about the relationship between variables such as customer satisfaction and buying behavior (Yang et al., 2018). Researchers can validate their theories and make informed decisions based on statistical evidence by conducting hypothesis testing. Furthermore, hypothesis testing theory allows for the identification of causal relationships between variables. This is important because understanding the factors that drive customer satisfaction and influence buying behavior can contribute to marketing strategies, product development, and overall business success (Busse & August 2021). Compared to other customer satisfaction theories, hypothesis testing theory provides a more rigorous and objective approach to understanding the relationship between customer satisfaction and buying behavior. Other customer satisfaction theories may rely on qualitative research methods or anecdotal evidence, which can be more subjective and prone to bias (Chen & Liu, 2013).\n\nIn contrast, this theory utilizes statistical techniques to analyze data and draw conclusions based on evidence. Overall, hypothesis testing theory is crucial in customer satisfaction research because it provides a systematic and data-driven approach to understanding the relationship between variables (Yang et al., 2018; Szymanski & Henard, 2001).\n\nUsing hypothesis testing, researchers can go beyond mere speculation and make evidence-based conclusions about the impact of customer satisfaction on buying behavior. The analysis of a nationally representative survey of 22,300 customers in Sweden in 1989-1990 revealed that satisfaction is best specified as a function of perceived quality and disconfirmation (Anderson & Sullivan, 1993). This suggests that when customers perceive high quality and experience a smaller gap between their expectations and the actual product or service performance, their satisfaction levels are higher (Szymanski & Henard, 2001; Lin, 2007; Yang et al., 2018; Chen & Chiu, 2018). Hypothesis testing theory enhances our understanding of the relationship between customer satisfaction and buying behavior, leading to informed business decisions.\n\nThe theory underscores the importance of managing customer expectations through accurate information and reliable performance, recognizing the role of disconfirmation in shaping satisfaction and understanding the impact of individual differences and dynamic expectations. By leveraging the insights from hypothesis testing theory, businesses can develop more effective strategies to meet and exceed customer expectations, ultimately enhancing satisfaction and loyalty. As the consumer landscape continues to evolve, adapting to the principles of hypothesis testing theory will be essential for sustaining competitive advantage and achieving long-term success.\n\nEquity theory examines the fairness of the exchange between a customer and a business. The theory suggests that customers compare the ratio of their inputs (such as money, time, and effort) to the outputs they receive (such as product quality, service, and overall experience) with the ratios of others (Ruyter & Wetzels, 2000). If customers perceive an imbalance in this exchange, it can result in dissatisfaction and potentially influence their buying behavior (Lin, 2007). In a highly competitive market, understanding equity theory is essential for businesses striving to satisfy their customers and retain their loyalty. By aligning the inputs and outputs to create a fair and equitable exchange, businesses can drive customer satisfaction and positively influence buying behavior (Ihemeje et al., 2020).\n\nUnderstanding the importance of equity theory in shaping customer satisfaction and buying behavior can provide businesses with valuable insights into attracting and retaining customers. By ensuring a fair and equal exchange, businesses can create a positive buying experience that leads to customer satisfaction and loyalty (Liu et al., 2008). Equity theory is a customer satisfaction theory in marketing that focuses on fairness. According to the theory, customers evaluate the fairness of their exchanges with a company based on the perceived balance between what they contribute (input) and what they receive (output) (Shao et al., 2009). This evaluation of fairness influences the customer’s overall satisfaction with the company and their future usage of its services (Ruyter & Wetzels, 2000). The theory suggests that if customers perceive an imbalance in the exchange, either in terms of high costs or inadequate benefits, they are likely to feel dissatisfied and may seek alternative options or disengage from the relationship with the company (Cugini et al., 2007). This theory suggests that companies should strive to create a sense of fairness and equity in customer interactions by aligning customer value with their expectations and treating all customers fairly and equally. Equity theory, as a customer satisfaction theory in marketing, emphasizes the importance of fairness in the exchange between customers and companies. By understanding and applying equity theory, marketers can enhance customer satisfaction by ensuring customers perceive a fair value exchange. Therefore, to optimize customer satisfaction, companies should provide customers with fair and balanced exchanges that align with their expectations (Davcik et al., 2015). Equity as a concept delves into the intricacies of customer-company interactions by examining the perceived balance between what the customer contributes and what they receive (Ruyter & Wetzels, 2000). It emphasizes the importance of fairness in these exchanges and sheds light on the consequences of perceived imbalances. When customers feel that the costs outweigh the benefits or vice versa, their satisfaction with the company is compromised, potentially leading them to explore alternative options or terminate their relationship with the company altogether (Terpstra & Verbeeten, 2014). Understanding equity theory helps businesses create fair interactions, enhance satisfaction, and build lasting customer relationships.\n\nPerceived fairness in Equity Theory accurately measures equity perceptions, considers cultural differences, understands the impact of digital interactions, integrates with other theories, incorporates emotional factors, and adapts to customer empowerment trends to enhance the theory’s robustness and applicability. As businesses navigate an increasingly complex and dynamic consumer landscape, addressing these challenges will help ensure that perceived fairness remains a cornerstone of customer satisfaction strategies.\n\nThe theory of perceived performance states that when a consumer’s expectations are ignored in their post-consumption or repeat purchase, a purchased service or product will perform in a very clear manner (Darawong & Sandmaung, 2019; Gandhi & Saini, 2013). It is inferred that consumer satisfaction evaluations are influenced mainly by perceived performance, regardless of prior expectations. This suggests that the perception of service/product quality alone is sufficient. The primary factor that determines pleasure is the performance of the service or product during consumption, without any comparison, which is generally known as “unapprised cognition” (Darawong & Sandmaung, 2019; Irfan, 2014).\n\nResearch has demonstrated that the perceived performance of a product or service is a crucial factor in determining customer satisfaction (Mohammed et al., 2017; Gottlieb and Beatson, 2018; Brown et al., 2008). Customer satisfaction is the subjective evaluation of how effectively a product or service fulfills the customer’s expectations. Research has indicated that customer satisfaction is influenced not just by the actual performance of a product or service but also by the customer’s expectations and their judgment of how well the product or service meets those expectations (Ganesh, 2023; Gottlieb and Beatson, 2018). The correlation between the quality of service and the perception of value is essential for comprehending customer satisfaction (Gottlieb and Beatson, 2018; Ganesh, 2023; Brown et al., 2008). Empirical research has continuously demonstrated that customer satisfaction is significantly impacted by the perceived performance of a product or service (Gottlieb and Beatson, 2018). Moreover, studies conducted in the restaurant sector have demonstrated that customer satisfaction is more closely linked to perceived performance rather than disconfirmation (Brown et al., 2008). Recognizing how perceived performance influences customer satisfaction is crucial for businesses to improve their overall reputation and cultivate customer loyalty.\n\nThe theory can be argued on the critical role of expectations, the impact of marketing and communication, and the use of feedback for continuous improvement. However, issues such as measuring perceived performance and expectations, cultural and contextual differences may have emotional and psychological concentration for further research. Addressing these gaps can enhance the theory’s applicability to consumer behavior and satisfaction.\n\n\nDiscussion\n\nThe focus of the review is presented with propositions that offer potential direction for future research. The review of the past studies indicates that there is a relationship between Expectation-Confirmation and Disconfirmation Paradigm in customer satisfaction theories to explain satisfaction formation. However, there are arguments for and against using this paradigm. The argument for the Expectation-Confirmation and Disconfirmation Paradigm is that it suggests that satisfaction is determined by the extent to which a product or service meets or exceeds pre-purchase expectations (Spreng et al., 1996). This paradigm assumes that individuals have specific expectations before purchasing a product or service, and their satisfaction is determined by whether those expectations are confirmed or disconfirmed. The argument against the Expectation-Confirmation and Disconfirmation Paradigm is that it oversimplifies the satisfaction formation process. Critics argue that satisfaction is a complex and multifaceted construct that cannot be solely explained by expectations and disconfirmation (Yüksel & Yüksel, 2001; Wirtz & Bateson, 1999). They believe other factors, such as individual motivations, emotions, and sociocultural contexts, also significantly shape satisfaction (Shirani et al., 2014).\n\nThe Adaptation Level Theory argues that satisfaction is influenced by a person’s adaptation level, which is their reference point for comparison (Spreng et al., 1996). This theory suggests that satisfaction is determined by pre-purchase expectations and a person’s adaptation to their current circumstances (Fournier & Mick, 1999). The Contrast Theory expands on this idea by emphasizing the role of the contrast between expectations and actual experiences in satisfaction formation (Ladhari, 2007). The Assimilation-Contrast Theory suggests that individuals may assimilate or contrast their experiences based on their initial expectations, influencing their satisfaction (Richardson, 1967). The Contrast Theory and Assimilation-Contrast Theory shed light on the role of cognitive processes in satisfaction formation. These theories emphasize how individuals may interpret their experiences based on their initial expectations, influencing their overall satisfaction. This highlights the intricate interplay between cognition and satisfaction, adding a layer of complexity to the understanding of customer satisfaction (Macieira et al., 2020).\n\nAs for the Value Percept Disparity Theory it suggests that satisfaction is influenced by the perceived difference between value received and value expected from a product or service (Sweeney & Soutar, 2001). Understanding the factors that shape this perception of value allows organizations to tailor their marketing strategies effectively, emphasizing the advantages of their offerings. By addressing inconsistencies between consumer expectations and actual experiences, businesses can enhance customer satisfaction and foster loyalty (Sánchez-Fernández & Iniesta-Bonillo, 2007). Additionally, recognizing the significance of post-purchase communication and assistance is crucial, as the consumer’s mental state after the purchase can impact future buying behavior and brand advocacy. Companies can leverage insights from this theory to differentiate their products or services from competitors by emphasizing unique value propositions that strongly resonate with consumers (Xu & Wyer, 2007).\n\nThe Cognitive Dissonance Theory proposes that satisfaction is influenced by the individual’s perception of the decision-making process and their post purchase rationalization (Fournier & Mick, 1999). The Comparison Level Theory of Satisfaction posits that individuals compare their satisfaction levels with a reference point or standard to evaluate their level of satisfaction (Jones et al., 2006). The Generalized Negativity Theory argues that satisfaction is influenced by individuals’ positive and negative experiences with a product or service. Their overall satisfaction is determined by the balance between these experiences (Spreng et al., 1996). The generalized negativity theory in customer satisfaction suggests that negative experiences or under-fulfillment of expectations influence overall satisfaction more than positive experiences (Thirumalai & Sinha, 2004). Negative experiences tend to have a stronger emotional impact and are more likely to be remembered and shared with others.\n\nHypothesis testing theory proposes that satisfaction is formed through hypothesis testing, where individuals compare their expectations with the actual outcomes and adjust their satisfaction accordingly (Biau et al., 2009; Mohammed et al., 2017). In context of Equity theory suggests that satisfaction is influenced by the perceived fairness of a transaction or exchange. In comparison, the Perceived Performance Theory posits that individuals form their satisfaction judgments based on their perceptions of the performance of a product or service (Pritchard, 1969).\n\nAnalyzing the importance of the cognitive dissonance theory, equity theory, and perceived performance theory offers valuable insights into satisfaction’s psychological and relational aspects. These theories underscore the importance of perceptions, fairness, and the actual performance of products or services in shaping satisfaction, expanding the scope beyond mere confirmation or disconfirmation of expectations (Pillai, 2021). As for the comparative level theory of satisfaction, it can possibly adapt to industrial applications where contentment is not an infinite occurrence. However, it is a relative determinant of customer experiences. Furthermore, it is contended that pleasure is ascertained by calculating the average of the benefits and drawbacks linked to an interaction and then comparing the outcome with the comparison level.\n\nIn marketing, the application of equity theory can significantly impact customer satisfaction. For instance, by aligning the value provided to customers with their expectations and ensuring that all customers are treated fairly and equally, companies can foster a sense of equity in their customer interactions (Nassè et al., 2020), particularly in terms of value proposition and value-driven strategy (Anand & Bansal, 2016). This, in turn, can lead to enhanced customer satisfaction and bolstered relationships between the company and its customers or consumers. To effectively optimize customer satisfaction, companies should focus on providing value to their customers and ensuring that their customers deem the perceived exchange of value fair and balanced (Shao et al., 2009). By incorporating equity theory into their marketing strategies, companies can actively assess and manage the fairness of their customer exchanges. This can be achieved through various means, such as transparent pricing strategies, effective value proposition communication, and responsive customer service. In addition, companies can also benefit from regularly assessing customer perceptions of fairness and actively addressing any perceived imbalances. In reference to perceived performance theory, empirical research has continuously demonstrated that customer satisfaction is significantly impacted by the perceived performance of a product or service (Gottlieb and Beatson, 2018). Studies conducted in the restaurant sector have demonstrated that customer satisfaction is more closely linked to perceived performance rather than disconfirmation (Brown et al., 2008; Gottlieb and Beatson, 2018).\n\nOverall, the argument for Expectation-Confirmation and Disconfirmation paradigm in these theories emphasizes the importance of expectations and their fulfillment in determining satisfaction. The argument against these theories’ Expectation-Confirmation and Disconfirmation paradigm is that it may oversimplify the satisfaction formation process. For example, the Adaptation Level Theory suggests that satisfaction is not solely determined by pre-purchase expectations but also by a person’s adaptation to their current experiences and circumstances (Fournier & Mick, 1999). This argument highlights the limitations of the Expectation-Confirmation and Disconfirmation paradigm in fully capturing the complexity of satisfaction formation. The argument for Expectation-Confirmation and Disconfirmation paradigm in these theories emphasizes the importance of expectations and their fulfillment in determining satisfaction. It recognizes that customers have pre-purchase expectations, and their post purchase evaluations are based on the extent to which those expectations were met or exceeded (Yüksel & Yüksel, 2001). For example, the Adaptation Level Theory suggests that satisfaction is not solely determined by pre-purchase expectations but also by a person’s adaptation to their current experiences and circumstances. The argument for Expectation-Confirmation and Disconfirmation paradigm in these theories is that it provides a straightforward and logical explanation for how satisfaction is formed. While the Expectation-Confirmation and Disconfirmation Paradigm provides a logical explanation for satisfaction formation, it becomes evident that this paradigm alone cannot fully encapsulate the multifaceted nature of satisfaction. The various theories presented highlight the need to consider a broader range of factors, such as cognitive processes, adaptation, perceptions, and interpersonal dynamics, in understanding the intricacies of customer satisfaction.\n\n\nConclusion\n\nExpectation-Confirmation and Disconfirmation Paradigm has been a dominant framework for understanding customer satisfaction, it is essential to recognize this paradigm. The Adaptation Level Theory, Contrast Theory, Assimilation-Contrast Theory, Cognitive Dissonance Theory, Equity Theory, and Perceived Performance Theory all provide valuable perspectives that contribute to a more comprehensive understanding of satisfaction formation. These theories emphasize satisfaction’s dynamic and multifaceted nature, highlighting the influence of adaptation, cognitive processes, perceptions, fairness, and interpersonal dynamics on satisfaction. By considering these diverse factors, the advantage can gain a more nuanced and holistic understanding of customer satisfaction. Therefore, while the Expectation-Confirmation and Disconfirmation Paradigm provides a logical explanation for satisfaction formation, it is essential to acknowledge the broader range of influences on satisfaction. Incorporating the insights from these theories can enrich our understanding of customer satisfaction and help businesses better meet their customers’ diverse and intricate needs.\n\n\nEthics and consent\n\nEthics and consent were not required.",
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USA: IEEE; 2005; pp. 1–10.\n\nKhongorzul G, Gerelmaa B, Kim W: A study on the effect of consumers’ online shopping styles on satisfaction and repurchase intention. Int. J. Adv. Appl. Sci. 2022; 9(7): 74–83.\n\nKokthi E, Kelemen-Erdős A: Assimilation-Contrast Theory: Support for the Effect of Brand in Consumer Preferences, Proceedings of FIKUSZ 2017.Fodor M, editor. Proceedings of FIKUSZ ’17. Óbuda University, Keleti Faculty of Business and Management; 2018; pp. 188–199.\n\nKotler P, Keller KL: Marketing Management. 13th ed.Upper Saddle River, NJ: Prentice Hall; 2009.\n\nLaczniak RN, Decarlo TE, Ramaswami SN: Consumers’ Responses to Negative Word-of-Mouth Communication: An Attribution Theory Perspective. J. Consum. Psychol. 2001; 11: 57–73. Publisher Full Text\n\nLadhari R: The movie experience: A revised approach to determinants of satisfaction. J. Bus. Res. 2007; 60(5): 454–462. Elsevier. 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Publisher Full Text\n\nMacieira F, Oliveira T, Yanaze MH: Models of satisfaction antecedents: a brief review. An integrative literature review of the most discussed satisfaction models in marketing studies. Int. J. Serv. Oper. Manag. 2020; 36(3): 348–359. Publisher Full Text\n\nMittal V, Han K, Frennea C, et al.: Customer satisfaction, loyalty behaviors, and firm financial performance: what 40 years of research tells us. Mark. Lett. 2023; 34(2): 171–187. Springer. Publisher Full Text\n\nMohammed GO, Hasaballah AHA, Almohaimmeed BMA, et al.: The impact of product performance on brand loyalty mediated by customer satisfaction: Study in Sudanese service industry. Int. J. Adv. Appl. Sci. 2017; 4(1): 116–122. Publisher Full Text\n\nMurray HA: Explorations in Personality. Oxford University Press; 1938.\n\nNassè T, Ouédraogo A, Takougang S, et al.: Equity and customer satisfaction in relation to product quality: evidence from three private companies in Burkina Faso. International Journal of Management & Entrepreneurship Research. 2020; 2(5): 344–352. Publisher Full Text\n\nOliver RL: A Cognitive Model of the Antecedents and Consequences of Satisfaction Decisions. J. Mark. Res. 1980; 17: 460–469. Publisher Full Text\n\nOliver RL, Winer RS: A framework for the formation and structure of consumer expectations: Review and propositions. J. Econ. Psychol. 1987; 8(4): 469–499. Publisher Full Text\n\nOshikawa S: The Theory of Cognitive Dissonance and Experimental Research. J. Mark. Res. 1968; 5(November): 429–430. Publisher Full Text\n\nPeyton R, Pitts S, Kamery H: Consumer Satisfaction/Dissatisfaction (CS/D): A Review of the Literature Prior to the 1990s. s.l. Proceedings of the Academy of Organizational Culture. 2003.\n\nPillai AV: Customer Happiness: The Role of Cognitive Dissonance and Customer Experience.Dutta T, Mandal MK, editors. Consumer Happiness: Multiple Perspectives. Studies in Rhythm Engineering. Singapore: Springer; 2021. 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(Developments in Marketing Science: Proceedings of the Academy of Marketing Science). Publisher Full Text\n\nSolomon MR: Consumer behavior: Buying, having, and being. 13th ed.Pearson; 2020.\n\nSpreng RA, MacKenzie SB, Olshavsky RW: A Reexamination of the Determinants of Consumer Satisfaction. J. Mark. 1996; 60(3): 15–32. Publisher Full Text\n\nSurprenant C, Churchill GA: An Investigation into the Determinants of Customer Satisfaction. J. Mark. Res. 1982; 19(November): 491–504. Publisher Full Text\n\nSweeney JC, Soutar GN: Consumer Perceived Value: The Development of a Multiple Item Scale. J. Retail. 2001; 77(2): 203–220. Publisher Full Text\n\nSzymanski DM, Henard DH: Customer Satisfaction: A Meta-Analysis of the Empirical Evidence. J. Acad. Mark. Sci. 2001; 29(1): 16–35. Publisher Full Text\n\nTerpstra M, Verbeeten FHM: Customer satisfaction: Cost driver or value driver? Empirical evidence from the financial services industry. Eur. Manag. J. 2014; vol. 32(3): 499–508. Elsevier. Publisher Full Text\n\nThirumalai S, Sinha K: Customer Satisfaction With Order Fulfillment in Retail Supply Chains: Implications of Product Type in Electronic B2C Transactions. J. Oper. Manag. 2004; 23: 291–303. Publisher Full Text\n\nTsai MH, Liao C, Hsieh RG: Customer dissemination of negative word-of-mouth: Influence of expected or unexpected events. Soc. Behav. Pers. 2014; 42(10): 1675–1687. Publisher Full Text\n\nUzir M, Hossain Uzir M, Jerin I, et al.: Does quality stimulate customer satisfaction where perceived value mediates and the usage of social media moderates? Heliyon. 2020; 6: e05710. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVedadi A, Kolobandi A, Pool HK: The Effect of Customer Value And Satisfaction on Customer Loyalty: The Moderating Role of Ethical Reputation. Int. Res. J. Basic Sci. Appl. Res. 2013; 2(5): 453–458.\n\nWestbrook RA, Reilly MD: Value-percept disparity: An alternative to the disconfirmation of expectations theory of consumer satisfaction. Adv. Consum. Res. 1983; 10: 256–261.\n\nWirtz J, Bateson JE: Consumer Satisfaction with Services: Integrating the Environment Perspective in Services Marketing into the Traditional Disconfirmation Paradigm. J. Bus. Res. 1999; 44: 55–66. Publisher Full Text\n\nXu AJ, Wyer RS: The Effect of Mind-Sets on Consumer Decision Strategies. J. Consum. Res. 2007; 34(4): 556–566. Publisher Full Text\n\nYang K, Chiang Y, Lin Y: A Study on Service Quality, Customer Satisfaction, and Customer Loyalty: The Case of PChome. Proceedings of the 2nd International Conference on E-Society, E-Education and E-Technology. 2018.\n\nYeh C-H, Wang Y-S, Li H-T, et al.: The effect of information presentation modes on tourists’ responses in Internet marketing: the moderating role of emotions. J. Travel Tour. Mark. 2017; 34: 1–15. Publisher Full Text\n\nYi Y: A Critical Review of Consumer Satisfaction.Zeithaml VA, editor. Review of Marketing. Chicago: American Marketing Association; 1990; pp. 68–123.\n\nYüksel A, Yüksel F: The Expectancy-Disconfirmation Paradigm: A Critique. J. Hosp. Tourism Res. 2001; 25(2): 107–131. Publisher Full Text"
}
|
[
{
"id": "353771",
"date": "23 Jan 2025",
"name": "Shankha Shubhra Goswami",
"expertise": [
"Reviewer Expertise Multi-criteria decision making (MCDM)",
"Optimization techniques",
"Fuzzy decision-making",
"Fuzzy optimization",
"Industrial engineering",
"Management",
"Soft computing",
"Production management"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview comments While the article provides a valuable theoretical perspective on consumer satisfaction and its connection to business sustainability, it lacks empirical evidence, practical applicability, and novel contributions. Addressing these concerns and providing a clearer link between theory and practice would significantly enhance its relevance and impact.\nThe article is purely conceptual, which limits its practical application and relevance to real-world business scenarios. Include empirical validation of the theories discussed by presenting case studies, surveys, or meta-analyses to enhance the paper's applicability. The paper revisits well-established paradigms without presenting significant advancements or novel insights. Propose new frameworks, alternative models, or integrations of the expectation-confirmation paradigm with emerging theories (e.g., digital consumer behavior or sustainability frameworks). While the paper aims to explore the causes and effects within the expectation-confirmation paradigm, the summary does not specify how these relationships are analyzed or supported. Clearly outline the methodology for identifying and evaluating causal relationships, even in a conceptual framework. The study seems to focus heavily on reviewing existing literature without offering actionable insights or practical recommendations. Dedicate a section to practical implications, detailing how businesses can leverage the findings to enhance customer satisfaction and sustainability. Although the title suggests a focus on decision-making, the summary does not provide sufficient detail on how the paradigm informs business decisions. Strengthen the discussion on how the expectation-confirmation paradigm directly influences strategic decision-making and long-term business growth. The paper appears to focus exclusively on the disconfirmation paradigm, overlooking other relevant consumer satisfaction theories (e.g., equity theory, SERVQUAL). Broaden the scope to include a comparative analysis of multiple consumer satisfaction theories to provide a more comprehensive understanding. While the paper mentions business sustainability, it does not elaborate on how consumer satisfaction theories contribute to sustainable growth strategies. Discuss specific mechanisms or examples where consumer satisfaction leads to sustainability, such as eco-friendly brand loyalty or sustainable product preferences. Terms like \"intention of confirmation\" and \"disconfirmation in satisfaction theories\" are vague and require further clarification. Provide clear definitions and examples to ensure the terminology is accessible to a broader audience. The summary suggests a lack of clarity in defining the study's objectives and contributions. Refine the abstract and introduction to clearly articulate the research questions, objectives, and expected contributions. The article states that the paper provides critical analyses but does not detail the criteria or framework for these analyses. Adopt a systematic approach to critique the literature, such as identifying strengths, weaknesses, and opportunities for future research. The inclusion of conceptual diagrams or models would enhance the paper's readability and impact. Add visual representations of the expectation-confirmation paradigm, causal relationships, or proposed frameworks. The research does not provide information on the structure of the paper, which may affect its readability. Ensure a logical flow, with clear sections for literature review, critical analysis, gaps, and implications. The summary mentions gaps but does not propose specific directions for future research. Provide actionable recommendations for future studies, such as exploring the paradigm in emerging markets or digital contexts.\nRecommendation: Major Revision Required\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1399
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https://f1000research.com/articles/13-1398/v1
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21 Nov 24
|
{
"type": "Research Article",
"title": "Exploring acenocoumarol and silodosin as allosteric EGFR inhibitors for the treatment of non-small cell lung cancer",
"authors": [
"Swastika Maity",
"Krishnaprasad Baby",
"Bharath Harohalli Byregowda",
"Megh Pravin Vithalkar",
"Usha Y Nayak",
"K Sreedhara Ranganath Pai",
"Yogendra Nayak",
"Swastika Maity",
"Krishnaprasad Baby",
"Bharath Harohalli Byregowda",
"Megh Pravin Vithalkar",
"Usha Y Nayak",
"K Sreedhara Ranganath Pai"
],
"abstract": "Background Non-small-cell lung cancer (NSCLC) is a highly morbid disease. Chemotherapy for NSCLC lacks specificity and efficacy mainly because of drug resistance. The current study aimed to explore computational tools to target allosteric epidermal growth factor receptor (EGFR) sites and screen for the top molecules in vitro and in vivo xenograft models.\n\nMethods Molecular docking, virtual screening, and molecular dynamic studies revealed that acenocoumarol and silodosin are the top two allosteric EGFR inhibitors. They were further tested for cytotoxicity, apoptosis, cell cycle, and gene expression by qPCR, western blotting, A549 cell xenograft anti-proliferative activity, and tumor regression efficacy analysis.\n\nResults Acenocoumarol and silodosin exhibited cytotoxicity in A549 and IMR-90 cells at concentrations below 50 and 80 μM, respectively. Acenocoumarol and silodosin induced S-phase and G2/M-phase arrest in A549 cells in the cell cycle analysis. Both drugs showed early apoptosis at their IC50 doses (acenocoumarol 50 μM and silodosin 25 μM). KRAS (Kirsten rat sarcoma viral oncogene homolog) and ERK2 (extracellular signal-regulated kinase 2) gene regulation in A549 cells was confirmed using qPCR. KRAS and ERK2 activities were quantified by western blot analysis. In the xenograft study, tumor size, body weight, and organ weight were significantly attenuated by the test drugs compared with the standard cisplatin. Immunoblotting and western blot results of the A549-xenograft tissue indicated downregulation of KRAS and ERK2. Furthermore, the test drugs have upregulated caspase-3 gene expression.\n\nConclusion The drugs acenocoumarol and silodosin downregulate KRAS and ERK2 both in cell line and in Xenograft model. KRAS and ERK2 are associated with EGFR inhibition. Hence, acenocoumarol and silodosin can be further explored for repurposing studies in human trials.",
"keywords": [
"Allosteric EGFR inhibitor",
"NSCLC",
"Acenocoumarol",
"Silodosin",
"Drug repurposing"
],
"content": "Introduction\n\nThe surface protein receptor tyrosine kinase (TK) and epidermal growth factor receptor (EGFR) are targets for many drugs, particularly for treating lung cancer.1 Mutation and alteration of EGFR in the cell lead to the development of NSCLC. Exon-19 multi-nucleotide frame deletion leads to the dimerization of four amino-acid sequences in the N-lobe of the EGFR complex, leading to single L858R and T750M or double T790M- L858R mutation condition.2 A single nucleotide substitution on Exon-21 in the EGFR site leads to ATP site activation, resulting in the replacement of arginine with leucine at L858M, causing a cancerous lung condition. In NSCLC, the Cys797 mutation to serine (C797S) occurs in the EGFR moiety.3 One of the major problems of EGFR-TK is autophosphorylation, leading to signal transduction pathways that activate the ATP region of the protein due to amino acid activation in the N-lobe of the EGFR complex, leading to an unstable EGFR moiety, causing cancerous growth in the cells.4 Therefore, targeted therapy against EGFR overactivity may be effective for treating NSCLC. Currently, the first-generation FDA-approved EGFR therapies are gefitinib and erlotinib, which bind to the ATP site of EGFR, but they fail to inhibit autophosphorylation due to the T790 mutation occurrence.5 Afatinib and dacomitinib, second-generation FDA-approved drugs, target the inactive site in EGFR and enzymatically inhibit the T790 mutation. The problem with these molecules is that they only recognize the dimeric state of EGFR and thus fail to stop EGFR overexpression in the monomeric state.6 The third-generation drug, osimertinib, has a pyrimidine moiety that covalently binds to the ATP site of EGFR. This leads to the selective inhibition of T790 expression. However, with long-term use, third-generation EGFR inhibitors show C797 secondary mutations.7 Tumor complexity and adaptive cell pathways for signalling in NSCLC, particularly involving the activation of various signalling pathways, such as amplification of MET/HER2, RAS-MAPK, or RAS-PI3K pathways, activate novel fusion events and histological or phenotypic transformation.8,9 Specific mutations, such as G796R, G796S, G796D, and L792H, and less prevalent mutations in exon 20 were linked with osimertinib resistance. Mutations such as C797S disrupt and weaken the covalent bond that Cys797 forms with osimertinib, preventing it from effectively targeting the mutant EGFR and thus conferring resistance to the drug.10\n\nFourth-generation drug development involves allosteric site inhibition of EGFR. Mutant-specific allosteric inhibitors of EGFR, such as EAI001, have been found to bind to sites beyond the EGFR allosteric site. This molecule was optimized to yield EAI045, which had potency towards L858R/T790M mutations compared to wild-type EGFR. Researchers have designed and optimized allosteric EGFR inhibitors that bind to allosteric sites in the EGFR tyrosine kinase domain outside the ATP domain and have emerged as potential treatment strategies for EGFR-mutant cancers.11 The main factor for choosing fourth-generation NSCLC drugs or allosteric EGFR inhibitors is that it reduces the chances of “undruggable” protein-ligand moiety formation, thus reducing the chance of adverse reactions of such drugs.12 In this study, we used computational tools to identify acenocoumarol and silodosin as top-2 allosteric EGFR inhibitors.13 These molecules were further evaluated for their pharmacological efficacy against NSCLC.\n\n\nMethods\n\nA549 cells (human lung carcinoma alveolar epithelial squamous cells) and IMR-90 (fibroblasts isolated from normal fetal lungs) were procured from American-type cell culture (ATCC®), and stock cells were cultured in RPMI 1640 medium (Life Technologies, Invitrogen, catalogue: 2187008), supplemented with 10% inactivated Fetal Bovine Serum (FBS, Merck Catalogue F7524), 100 IU/ml penicillin, and 100 μg/ml streptomycin (Thermo Fisher Scientific®) in a humidified atmosphere of 5% CO2 at 37oC until confluent. The cells were dissociated with cell dissociating solution containing 0.2% trypsin (Invitrogen; catalog R-001-100), 0.02 % EDTA, and 0.05% glucose in PBS. Further, 50,000 cells/well were seeded in a 96-well plate and incubated for 24 hrs at 37oC, 5 % CO2 incubator (MIC-80; Microsil India Pvt. Ltd.) The cell viability is checked using a hemocytometer (Rohem Silverline Counting Chamber). The required amount of cells were further cultured in a T75 culture flask (Thermo Fisher Scientific).13\n\nThe top molecules from the in silico studies, danusertib, bifonazole, clopidogrel, acenocoumarol, silodosin, panobinostat, and standard doxorubicin were procured from TCI® India. The stock solution of test compounds 10 mM stocks was prepared using DMSO (dimethyl sulfoxide, TCI India). Serial two-fold dilutions were prepared from 100 μM to 3.125 μM using RPMI 1640 plain media for respective treatments.13 Cytotoxicity in A549 and IMR-90 cells were carried out using MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) reagent.14 The monolayer cell culture was trypsinized and the cell count was adjusted to 5 × 105 cells/ml using respective media containing 10% FBS. To each well of the 96-well plate, 100 μl of the diluted cell suspension (50,000 cells/well) was added. After 24 h, when a partial monolayer was formed, the supernatant was flicked off, washed the monolayer once with medium and 100 μl of different test concentrations of test drugs were added onto the partial monolayer in microtiter plates. The plates were then incubated at 37oC for 24 h in 5% CO2 atmosphere. After incubation, the test solutions in the wells were discarded, and 100 μl of MTT (5 mg/10 ml in PBS) was added to each well. The plates were incubated for 4 h at 37oC in 5% CO2 atmosphere. The supernatant was removed, and 100 μl DMSO was added, and the plates were gently shaken to solubilize the formed formazan.15 Absorbance was measured using a microplate reader (BMG LABTECH®) at 590 nm. The percentage growth inhibition was calculated using the following formula\n\nThe half maximal inhibitory concentration (IC50) values for cytotoxicity tests were derived from non-linear regression analysis performed using GraphPad Prism8.0 (Graph pad, San Diego, USA). Alternatively, R-program can also be used. The results were compared between groups. From the cytotoxicity results, we selected the best drugs, acenocoumarol and silodosin, for further testing.\n\nA549 cells (1 × 106 in RPMI buffer), were used in this study. The plates were analyzed using a flow cytometer (FACS Calibur, BD Biosciences, San Jose, USA). After 18 h of incubation, the floating cells were replaced with the new medium. Control, standard and test samples at different concentrations were added, followed by induction of apoptosis. Cells were scraped and 1 ml of medium was pipetted to the wells. After the cells were washed twice with cold PBS, they were resuspended in a binding buffer at 1 × 106 cells/ml. The cell suspension was portioned to 500 μl, to which 5 μl of Annexin V (Annexin V, FITC detection kit, Sigma-Aldrich®) and 10 μl of propidium iodide (Sigma-Aldrich) were mixed. The plates are stored in the dark for 15 min, followed by analysis with a flow cytometer. The quadrants were created based on viable cell markers with different colors.16 Gating was performed, and cell apoptosis was measured and compared in the different treatment groups.\n\nA549 cells (1 × 106 cells/ml) were cultured and kept at 6 well plates with 2 ml of RPMI medium and incubated for 24 h. It was then subjected to treatment with the test drugs acenocoumarol (25 and 50 μM), silodosin (12.5 and 25 μM), and standard doxorubicin (25 μM) were incubated for 24 h. The cells were then harvested and centrifuged at 2000 rpm for 5 min at room temperature, and the supernatant was discarded carefully, retaining the cell pellet. The cell pellet was washed by resuspending in 2 ml of 1XPBS. The washing was repeated another time with the same conditions. The supernatant was then discarded. From the pellet, the cells were fixed by resuspending in 300 μl of Sheath fluid (BD Bioscience®, catalogue no:342003), followed by the addition of 1 ml of chilled 70% ethyl alcohol drop by drop with continuous gentle shaking and another 1 ml of chilled 70% ethyl alcohol added at once. The cells were then stored at 4°C for or overnight. Post fixing, the cells were centrifuged at 2000 rpm for 5 min. The cell pellet was washed twice with 2 ml of cold 1X PBS. The cell pellet was then resuspended in 450 μl of sheath fluid containing 0.05 mg/ml PI (Sigma-Aldrich catalogue no: P4864), and 0.05 mg/ml RNaseA (Sigma-Aldrich, catalogue no: P4864) and incubated for 15 min in the dark. The percentage of cells in different stages of the cell cycle in compounds treated and untreated populations were determined using FACS Caliber (BD Biosciences, San Jose, CA).17\n\nA549 cells (10 × 106 cells/2 ml) were cultured in RPMI medium, added to P35 dish, and incubated till 80% confluency. Drug treatment with acenocoumarol (25 and 50 μM), silodosin (12.5 and 25 μM), and standard doxorubicin (25 μM) were were incubated for 24 h. The protein was isolated post-harvesting by washing with PBS solution twice. The cell pellet was suspended in 300 μl of Radioimmunoprecipitation assay (RIPA) buffer (Thermo-Fisher Scientific) with 1X protease inhibitor (Sigma-Aldrich). The cells were incubated for 30 min, but every 5 min, the suspension was mixed. Then, cells were centrifuged at 10,000 rpm for 12 min and protein lysates were collected. The protein lysates were mixed with 5X loading dye and heated for 2 min at 95°C. Further, it was loaded with 10% and 15% sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE) using Mini protean Tetra cell (Bio-Rad). The nitrocellulose membrane (0.2 μM) (Bio-Rad) was equilibrated in transfer buffer for 10 min. Protein transfer was done for 15 min in the Turbo Transblot (Bio-Rad) apparatus. The blot was blocked in 3% bovine serum albumin (BSA) in tris-buffered saline with Tween 20 (TBST, Thermo-Fisher Scientific, Catalogue no. A11008) for 1 h. The blot was incubated with 2° Ab (anti-Rabbit or anti-Mouse IgG-HRP (horseradish peroxidase, Thermo-Fisher Scientific) at dilution 1:10000 for 1 h. The blot was rinsed with enhanced chemiluminescence (ECL) reagent (Thermo-Fischer Scientific), for 1 min in the dark, and the images were captured between 0.5 to 5 s exposure in Chemidoc XRS and imaging system (Bio-Rad).17 The protein expression levels of KRAS and ERK2 were measured, keeping glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as loading control in this study and the fold regulation was calculated.\n\nTreated A549 cells were scraped and washed with sterile PBS, followed by centrifugation at 12,000 rpm for 5 min at 4°C. The supernatant was discarded, and 0.4 ml of TRIzol (Invitrogen - Life Technologies®) was added, mixed for 1 min, and allowed to stand for 10 min at room temperature. Chloroform (0.25 ml per 0.4 ml of TRIzol) was added, and the mixture was vortexed for 15 s. The tube was left to stand for 5 min, after which it was centrifuged at 12,000 rpm for 15 min at 4°C. The aqueous phase was carefully transferred to a new sterile microcentrifuge tube. Isopropanol (0.5 ml) was added, gently mixed for 30 s, and incubated at -20°C for 20 min. The mixture was centrifuged at 12,000 rpm for 10 min at 4°C. After removing the supernatant, the RNA pellet was washed with 0.5 ml of 70% ethanol and centrifuged at 12,000 rpm at 4°C. The supernatant was discarded, and the RNA pellet was air-dried. The pellet was resuspended in 20 μl of diethylpyrocarbonate (DEPC)-treated water, and the total RNA yield was quantified using SpectraDrop (SpectraMax i3x, Molecular Devices, USA). cDNA was synthesized from 500 ng of RNA using the PrimeScript RT reagent kit (Takara Bio) with oligo (dT) primers (Thermo-Fisher), according to the manufacturer’s instructions, in a reaction volume of 20 μl. The cDNA synthesis was performed at 50°C for 30 min. The synthesized cDNA was used for real-time polymerase chain reaction (RT-PCR) analysis. Each 20 μl PCR mixture contained 1.4 μl of cDNA, 10 μl of SYBR Green Master Mix (Thermo Fisher Scientific), and 1 μM of specific forward and reverse primers for the target genes ( Table 1).13 The PCR reaction began with enzyme activation at 95°C for 2 min, followed by 39 cycles of denaturation at 95°C for 5 s, and annealing/extension at the appropriate temperature for 30 s. A secondary denaturation at 95°C for 5 s was performed, followed by a melt curve analysis from 65°C to 95°C in 5°C increments. Fold expression or regulation was calculated and compared between treated groups.18,19\n\nThe study was performed with prior approval from Institutional Animal Ethics Committee (IAEC) approval and as per the guidelines of the CPCSEA, and followed ARRIVE 2.0 checklist.13 Nude mice (n=16, four groups) were used for the Xenograft induction and treatment. A549 cells at a sub-confluent level were harvested, and viable cells were counted using a haemocytometer. Post viability check, a single cell suspension of 5 x107 cells/ml was prepared in serum-free media and mixed in matrigel at a 1:1 ratio. All the mice were subcutaneously injected with 0.2 ml of cell suspension in the region above the right flank region.20,21 Tumor size was analyzed using digital Vernier callipers. Treatment with was started when the tumor size was 100-150 mm3 (2 weeks). Treatment with the test drugs and standard drugs was initiated as per the respective pre-determined doses, the positive control was intravenously administered, and test drugs were administered to animals in groups 3 and 4. Tumor length and width were measured every alternate day using Vernier calipers, and tumor volume was calculated. Once the tumor size reached the desired volume, ≈100-150 mm3 (3 weeks), the tumor volume was noted and randomly sorted into four groups, each consisting of four animals. The treatment groups contained the tumor control group, to which normal saline was administered orally; the positive control group mice were treated with 4 mg/kg cisplatin (TCI, India; CAS: 15663-27-1; catalogue no: D3371), and the test sample or treatment groups III and IV received an oral dose of silodosin at 8 mg/kg and acenocoumarol at 0.2 mg/kg till 21 days. At the end of the study, the mice were euthanized. The parameters such as tumor volume, % tumor growth inhibition, % change in body weight, organ weights, mean tumor weight.22 All efforts were made to reduce the suffering of the animals throughout the study phase.13\n\nThe caspase-3 regulation in A549-xenograft tissue gene expression were analyzed and compared between the treatment groups.23 The specific forward and reverse primers for the target genes are represented in Table 2.\n\nWestern blot analysis was performed and the Ref. 24. The respective markers were analyzed in this study.\n\nThe histopathology, hematoxylin and eosin (H&E) staining of tumour tissue, heart, kidney, liver, lung, and spleen were carried out.25 Cell infiltration, cell rupture, and cellular confluence were analyzed to identify the effects of the treatment group compared to the control group.\n\n\nResults\n\nIn A549 cells, cytotoxicity analysis by MTT assay showed potent cell death in all treated drugs. Silodosin, danusatib, acenocoumarol, and panobinostat were more potent than the others. The IC50 values are presented in Figure 1. The IC50 in IMR-90 cells are presented in Figure 2. Acenocoumarol and silodosin were more potent than panobinostat and danusatib. Based on the IC50 of the drugs acting on both cell lines, acenocoumarol and silodosin were selected for further in vitro analysis to analyze their efficacy in treating NSCLC and their antagonistic activity as EGFR allosteric inhibitors.\n\nLegend: The data presented by treatment groups is compared against control and doxorubicin. Drugs such as Bifonazol and clopidogrel did not show IC50, and hence, they are not represented in the figure.\n\nCell activity was observed in all four quadrants compared with that in the control group. The control group showed activity in the first quadrant, indicating the presence of highly viable cells ( Figure 3). This result reflects a significant decrease in cells due to the effect of treatment. The acenocoumarol treatment at 25 μM and 50 μM has induced 20.25%, 36.9% early apoptosis and 11.28%, 6.14% late apoptosis, whereas sample silodosin showed 33.49%, 36.09% early apoptosis and 16.21%, 24.84% late apoptosis at 12.5 μM and 25 μM treatment in A549 cells. Standard doxorubicin at 25 μM has shown total apoptosis of 54.24% in A549 cells ( Figure 4). The PI flow cytometry method on A549 cells in the treatment groups showed increased cell apoptosis compared to the control group. Groups such as acenocoumarol and silodosin showed earlier apoptosis when compared to doxorubicin. Silodosin at 25 μM induced more apoptosis than other treatments at different doses, as determined by Annexin V-FITC and propidium iodide (PI) staining and flow cytometry analysis.\n\nLegend: The experimental groups: vehicle control, standard control (Doxorubicin 25 μM), and Treatment groups, namely Acenocoumarol at concentrations 25 μM and 50 μM, silodosin at concentrations 12.5 and 25 μM. The viable cell population was determined at the bottom left of the quadrant of the plot. Early apoptotic cells were identified at the bottom right quadrant, and late apoptotic cells were indicated at the top right quadrant.\n\nLegend: The x-axis presents the treatment groups. Doxorubicin was the standard control. The y-axis represents the percentage of apoptosis activity. The graph shows the effect of treatment groups on checking viable cells, early apoptosis, late apoptosis and necrotic cell analysis. The data is presented by two-way ANOVA without replicas compared to doxorubicin with Mean±SEM. p<0.05, ** and p<0.5, *; compared to doxorubicin 25 μM.\n\nThe separation of cancer cells in the G0/1, S, and G2/M phases was demonstrated using flow cytometry analysis based on the fluorescence intensity of PI-stained cancer cells. The control group contained cells in the G0/G1 phase. The treatment of A549 cells at the concentrations of 25μM and 50μM with Sample acenocoumarol resulted in S phase and G2M phase arrest of 4.93%, 25.29%, and 10.19%, 15.15%, respectively, and Sample Silodosin has shown 13.7%, 33.37% S phase arrest, 14.82%, 19.43% G2M phase arrest at test concentrations 12.5 μM and 25 μM, respectively, in A549 cells. Standard doxorubicin at 25 μM induced G2M arrest of 31.61% and S phase arrest of 20.92%, respectively, in A549 cells. The test drugs showed significant G1 and S peaks compared with the standard control ( Figures 5 and 6). Acenocoumarol and silodosin treatment at 50 μM and 25 μM induced a significant decrease in the percentage of cells in the G1 phase, and an accumulation of cells in the S and G2/M phases of the cell cycle indicated cell cycle arrest at the S and G2M phase.\n\nLegend: Cell cycle activity in A549 cells with respective treatment conditions. The x-axis presents the propidium iodide-induced fluorescence; the y-axis presents the cell frequency. The stages of the cell cycle are marked as a: Go/G1, b: S, c: G2 M and d: SUB Go, respectively. Doxorubicin 25 μM, is the standard used for comparison.\n\nLegend: Cell cycle stages are presented as SUB Go, Go/G1, S and G2 M phases marked with different colours. Vehicle control, Standard control (Doxorubicin 25 μM), Treatment groups namely Acenocoumarol (25 μM and 50 μM), Silodosin (12.5 and 25 μM). The data was analysed by two-way ANOVA without replicas compared to doxorubicin with Mean ± SEM. p<0.05, ** and p<0.5, *; compared to doxorubicin 25 μM.\n\nThe Western blot results of A549 cells treated with acenocoumarol at 25 and 50 μM concentrations suggested that KRAS and ERK2 were downregulated by 2.12-, 3.50-, 1.04-, 1.68-fold, respectively. KRAS expression was found to be downregulated in cells treated with Silodosin at 12.5 and 25 μM by up to 1.08 and 1.71 folds. ERK2 expression was upregulated when treated with Silodosin at 12.5 μM and 25 μM ( Figure 7). The standard group showed downregulation of both KRAS and ERK2 by up to 3.02 and 2.41, respectively.\n\nLegend: A: Representation of western blot gels. The treatment groups are presented as lane a: vehicle control, b: acenocoumarol 25 μM, c: acenocoumarol 50 μM, d: silodosin 12.5 μM, e: silodosin 25 μM, f: standard control, doxorubicin 25 μM. B: Fold analysis to determine the level of expression.\n\nqPCR or quantitative PCR analysis of the target genes KRAS and ERK2 was carried out, and fold regulation was determined. The results suggested decreased KRAS and ERK2 expression in cells treated with acenocoumarol at 50 μM compared to the control, with 2.10- and 1.57-fold expression. Acenocoumarol at 25 μM showed only a negligible effect on KRAS expression, whereas ERK2 was observed to be positively upregulated 0.31-fold ( Figure 8) compared to the control. The gene expression of both KRAS and ERK2 was upregulated in cells treated with silodosin at 12.5 μM. The expression was observed to decrease as the treatment concentration increased, with 6.54- and 1.72-fold in KRAS and ERK2 expression, respectively. The standard treatment has shown decreased expression by 3.12- and 1.49-fold in KRAS and ERK2 expression ( Figure 9).\n\nLegend: The x-axis shows the drug treatments and the y-axis shows a fold change frequency by qPCR analysis. The treatment groups are vehicle control and standard control i.e. Doxorubicin 25 μM. Treatment groups namely Acenocoumarol at concentrations 25 μM and 50 μM, and silodosin at concentrations 12.5 and 25 μM.\n\nLegend: A. Tumor growth profile (mm3) during the treatment period of 21 days; B. Tumour induction in nude mice and its growth profile at the end of the study. In the disease control group (cisplatin 4 mg/kg), silodosin (8 mg/kg), and acenocoumarol (0.2 mg/kg), Values are represented as Mean ± SEM (n= 4). p<0.5 significant compared to the vehicle control.\n\nThe mice with A549 Xenografts treated with Cisplatin showed a tumor growth inhibition up to 73.57 ± 0.88 whereas, the test drugs showed inhibition up to 22.69 ± 3.79 and 45.3 ± 5.32% at 8 mg/kg and 0.2 mg/kg respectively (p<0.05, p<0.5) ( Figure 9). The tumor growth profile of all treatment groups was significantly reduced, indicating that the test drug showed good efficacy against NSCLC. Tumor growth inhibition was significant compared to that in control mice ( Figure 10). Other organ growth profiles suggested that the groups with treatment induction had good growth profiles compared with the disease control groups ( Figure 11).\n\nLegend: The disease control group i.e. cisplatin (4 mg/kg) showed significant tumour growth with p<0.001; the treatment groups silodosin 8 mg/kg and acenocoumarol (0.2 mg/kg) showed significant tumour growth inhibition profile against vehicle control (p<0.001). Data represented in Mean ± SEM was calculated.\n\nLegend: The vehicle control is disease-induced mice, cisplatin (4 mg/kg), silodosin (8 mg/kg), and acenocoumarol (0.2 mg/kg). Values are represented as Mean ± SEM, p< 0.05 is considered significant compared to vehicle control.\n\nqPCR analysis of the A549 xenograft treated with silodosin and acenocoumarol at pre-determined concentrations suggested the effective upregulation of Caspase-3 gene expression in tumor tissue samples. The tumor tissue from silodosin and acenocoumarol showed upregulation of Caspase-3 gene expression by 5.82- and 1.49-folds ( Figure 12), respectively, when compared to the control. In contrast, standard treatment with cisplatin resulted in a 1.71-fold increase in expression. Overall, the results suggest that the test sample treatment with silodosin and acenocoumarol at the respective concentrations was effective in the A549 xenograft model.\n\nLegend: The treatment groups namely Silodosin (8 mg/kg), acenocoumarol (0.2 mg/kg) and the disease control group, cisplatin (4 mg/kg) were compared to vehicle control (medium).\n\nIn the blot analysis of the treatment groups, Acenocoumarol 0.2 mg/kg and silodosin (8 mg/kg) were analyzed for KRAS and ERK2 enzyme fold regulation ( Figure 13). The blots (Figure 13B) show upregulation of KRAS, whereas ERK2 was downregulated very little, except with acenocoumarol treatment. Acenocoumarol showed better activity than the standard and silodosin treatments did.\n\nLegend: A: The treatment groups, namely Silodosin (8 mg/kg), acenocoumarol (0.2 mg/kg) and the disease control group, cisplatin (4 mg/kg), were compared to vehicle control (medium). B: The enzymatic degradation study of KRAS, GAPDH and ERK2 marker. The groups evaluated for fold regulation were a,b: vehicle control; c,d: disease control; e,f: Silodosin (8 mg/kg) and g,h: acenocoumarol: (0.2 mg/kg).\n\nTumor analysis of the histopathology test ( Figure 14) showed that A/group I: Normal architecture was observed. B/group II: Necrosis with moderate mononuclear cell infiltration. C/group III: mild necrosis with mild mononuclear cell infiltration. D/group IV: moderate mononuclear cells. Silodosin and acenocoumarol showed good anti-NSCLC activity compared with the disease control group. The arrows in Figure 14 show cell infiltration/inflammation. The treatment groups showed less cell infiltration than the vehicle-disease control group, indicating suppression of cancerous activity.\n\nLegend: A: lungs, B: Tumor, C: Liver and D: Kidney.\n\n\nDiscussion\n\nEGFR is the major oncogene driver in NSCLC, and EGFR-targeted therapy has the potential to deliver greater suppression of aggressive NSCLC compared to cytotoxicity-based pharmacotherapy.26 Drugs that target the allosteric site of EGFR-TK, disrupt the cell-signalling cascade and alter cellular function.27 The allosteric site has attracted significant interest from researchers and is now regarded as a highly promising target for developing anti-NSCLC drugs. Therefore, this study highlights the significance of inhibiting the EGFR allosteric site, which intersects with the TK receptor-ligand interaction.28 It has also been stated that anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS1), kinase-renin-angiotensin system (KRAS), protein kinase B (PKB), or (AKT) are other validated tissue biomarkers in NSCLC due to its downregulation of EGFR kinase in cell proliferation.29 Targeting the allosteric site stabilizes the protein complex, influencing the binding efficiency of the primary ligand. This inactivates the protein and reduces the responsiveness to ligands or results in a neutral effect during ligand interactions. Consequently, allosteric sites have the ability to disrupt or fully halt the signal transduction process. Moreover, the site remained stable throughout the interaction. As a result, allosteric site targeting can effectively suppress cellular proliferation, particularly in malignant conditions, with allosteric inhibitors showing high selectivity.12\n\nAcenocoumarol is an oral anticoagulant primarily used for the prevention and treatment of thromboembolic disorders. It inhibits the synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X) in the liver, which are essential for blood clot formation. This action helps prevent the formation of new blood clots and the growth of existing clots.30 Silodosin is an alpha-1 adrenergic receptor antagonist primarily used for the treatment of benign prostatic hyperplasia (BPH), a condition characterized by an enlarged prostate gland that can cause urinary symptoms in men.31 Acenocoumarol is a coumarin derivative with an active chiral core that is present in the enantiomeric form.32 Acenocoumarol is absorbed by the gastrointestinal tract and undergoes first-pass metabolism, which results in peak plasma levels after dosing. In addition, if not administered in lower doses, it may lead to thromboembolic events.33 A study indicated that acenocoumarol can upregulate extracellular signal-regulated kinase 2 (ERK1/2), leading to the activation of phosphorylation in the TK pathway. Acenocoumarol also affects the PI3K/AkT, MAPK, and RAS pathways by controlling the TK moiety.34\n\nEnzymes ERK2 and KRAS significantly inhibited enzymatic activity upon administration of silodosin. Hence, silodosin inhibits cell proliferation in NSCLC by inhibiting the signal transduction cascade, MAPKs, ERK, and k-RAS, which can stop aggressive growth, leading to potent anti-NSCLC activity. An earlier report showed that silodosin was able to produce pro-apoptotic activity in bladder cancer cells by enhancing the cytotoxic activity of cisplatin via ELK1 inactivation.35 Silodosin is produced by α-androgenic blockers. Silodosin is the treatment of choice for lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).36 Signal transduction in the TK complex via phosphorylation at certain sites in response to MAPKs and ERK. ELK-1 activation has been reported to demonstrate pro-apoptotic activity within the cytoplasm and pro-differentiation activity inside the nucleus of cancer cells, which lowers aggressive cell proliferation.37 The degradation products of silodosin also exhibited anticancer activity.38 Hence, silodosin could be repurposed as an anti-NSCLC drug.\n\nAllosteric inhibition of EGFR can prevent the autophosphorylation of tyrosine residues, blocking the recruitment of Grb2 (Growth factor receptor-bound protein 2) and Son of Sevenless (SOS), which are essential for KRAS activation.39 ERK2 is the downstream regulator of KRAS in the RAS-RAF-MEK-ERK pathway; hence, activation depends on upstream signals, such as EGFR.40 Hence, allosteric EGFR affects the activation of KRAS, which cascades through RAF and MEK to influence ERK2 phosphorylation. In this study, when enzymes ERK2 and KRAS were examined for their activity following the administration of silodosin, they demonstrated upregulated activity by exhibiting considerable enzymatic inhibition. We can conclude that silodosin and acenocomerol were able to reduce cell proliferation in NSCLC by suppressing the signal transduction cascade, MAPKs, ERK, and KRAS. Silodosin was able to promote pro-apoptotic activity in cancer cells and inhibit aggressive cancer growth, leading to significant anti-NSCLC activity that could be attributed to its allosteric EGFR inhibition.\n\n\nConclusion\n\nThe in silico study inferred that acenocoumarol and silodosin have an affinity for EGFR allosteric sites. Acenocoumarol and silodosin were subjected to a series of in vitro and A549 xenograft analyses to evaluate their potencies. Both drugs showed significant effects on A549 cells and were able to control the overexpression of ERK2 and KRAS. These drugs can be further explored in clinical trials to determine the efficacy of these drugs as fourth-generation anti-NSCLC agents.\n\n\nEthics considerations\n\nThe study was approved by the Institute’s Ethical Committee as per IAEC guidelines, and the Arrive Guidelines 2.0 was archived. The ethics approval no. for the study was IAEC-SLS-2022-071 (Date: 25th October 2022). All studies and animal handling were performed strictly according to the IAEC guidelines, and the ARRIVE 2.0 Checklist was archived.13\n\n\nAuthor contributions\n\nSwastika Maity: Conceptualization, Data curation, formal analysis, Investigation, Methodology, Project administration, writing the original draft, and editing.\n\nKrishnaprasad Baby: Methodology, Formal analysis, Validation\n\nBharath Harohalli Byregowda: Methodology, Formal analysis, writing- review and editing\n\nMegh Pravin Vithalkar: Methodology, Formal analysis, Visualization\n\nUsha Y Nayak: Supervision, Validation, Resources\n\nK Sreedhara Ranganath Pai: Supervision, Validation, Conceptualization.\n\nYogendra Nayak: Conceptualization, formal analysis, methodology, data curation, supervision, funding acquisition, writing, review, and editing.",
"appendix": "Data availability\n\nUnderlying data archived at Figshare https://doi.org/10.6084/m9.figshare.24587592.v5.13\n\nThis project contains the following underlying data:\n\nARRIVE-2.0_checklist.pdf\n\nSupplementary_file-1.docx (Data generated by in silico studies)\n\nSupplementary_file-2.docx (Data generated by in vitro and in vivo studies)\n\nMethods in Detail 1.docx (Detailed materials and methods for in vitro and in vivo studies)\n\nResults.xlsx (Contains the in vitro and in vivo data)\n\nImages- SDS.pptx (Contains the original images of western blots)\n\n\nAcknowledgement\n\nThe authors are thankful to the Manipal Academy of Higher Education, Manipal for the Financial support, and Dr. TMA Pai PhD Fellowship to Krishnaprasad Baby, Bharath Harohalli Byregowda, and Megh Pravin Vithalkar.\n\n\nReferences\n\nIyer RS, Needham SR, Galdadas I, et al.: Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers. Nat. 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}
|
[
{
"id": "343035",
"date": "03 Dec 2024",
"name": "Tyler Beyett",
"expertise": [
"Reviewer Expertise EGFR pharmacology including allosteric inhibitor discovery and development"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this article, Maity et al. explore the effects of acenocoumarol and silodosin treatment on primarily on A549 cells. They show that high doses of either molecule induce apoptosis in cell culture and have a slight, but significant, effect in xenograft models. Overall, I have major concerns about the interpretation of the results. While I believe the data showing that these molecules are cytotoxic, I am not convinced that it is through inhibition of EGFR.\nSpecific major points:\n\nMy biggest concern with this manuscript is the multiple references to these molecules as allosteric EGFR inhibitors. For example, in the manuscript title and the last sentence of the discussion. No data are presented in this study showing inhibition of EGFR by acenocoumarol or silodosin. There are also no data showing that they work through an allosteric mechanism of action. No allosteric inhibition data are provided in the reference prior work (reference 13) either. This reference only describes docking of the molecules and is lacking controls/reference molecules such as known allosteric EGFR inhibitors like EAI045 and JBJ-09-063. Docking is only a prediction that still requires experimental validation (protein-ligand binding analysis, biochemical kinase inhibition assay, cellular inhibition by phospho-EGFR western blot, etc.). Confirming an allosteric mechanism of action requires a crystal structure or enzymatic inhibition assays with varying ATP concentrations. For these reasons, the multiple claims that these molecules are allosteric EGFR inhibitors cannot be made, and this study must be presented/worded differently as a result. Related to the previous point, since inhibition of EGFR has not been shown, it cannot be assumed that the cytotoxic effects observed are related to EGFR. Performing a target engagement assay would aid in showing the effects are on target rather than working through another mechanism/pathway to induce apoptosis. Many compounds will induce cell death. Throughout the manuscript, critical details about experimental replicate (n) number are missing. The number of biological and technical replicates must be noted for all experiments. This is especially important since SEM is being reported, which is affected by n. Throughout the manuscript, relevant controls including known EGFR inhibitors, ATP-competitive and allosteric, are missing. Cisplatin is not the standard of care for the vast majority of EGFR-driven cancers and thus is not an ideal reference compound. As A549 cells are do not express mutant EGFR (they overexpress wild-type EGFR), a pan-EGFR inhibitor like afatinib is an ideal positive control. In the MTT cytotoxicity assay it is difficult to see where the IC50s are being derived from for some molecules. IC50 is defined as the inflection point of a sigmoidal curve, but many of these curves do not have such a point and do not appear to encompass enough of the dose-response curve to accurately report an IC50. Inclusion of EGFR inhibitors as controls, especially allosteric inhibitors, is needed for a frame of reference since IC50s are condition dependent. Additionally, it is not clear why acenocoumarol and silodosin were chosen. It is claimed that “From the cytotoxicity results, we selected the best drugs, acenocoumarol and silodosin, for further testing.” These molecules were not consistently more potent than the others. What wasn’t danusertib selected? It is most potent against the cancer cell line and least potent against the healthy cell line, which is typically the desired profile of a targeted therapy. The section titled “KRAS and ERK2 enzymatic inhibition by acenocoumarol and silodosin” is misleading as no inhibition data are presented. That section only provides data on total protein levels. Furthermore, it appears as if this experiment was only performed once. Given the potential for bias in quantifying western blot bands by densitometry, especially weak bands, this experiment must be performed multiple times and error bars reported. Related to the previous point, in the discussion it is stated that “Enzymes ERK2 and KRAS significantly inhibited enzymatic activity upon administration of silodosin” and “suppressing the signal transduction cascade.” This and related statements need to be removed, as enzymatic activity and signal transduction of ERK2 (typically assessed by phospho-ERK blotting) or activation of RAS (assaying for GTP bound state or GTPase activity) are not assessed. Furthermore, the use of “significantly” is inappropriate given that no statistical analyses were performed in the relevant figures 7 and 8. Information on the statistical tests used in Figures 9, 10, and 11 are missing. The related figures 7 and 8 do not make sense. For example, 12.5 uM silodosin greatly decreases expression, but the protein levels are not dramatically decreased. Similarly, for 25 uM acenocoumarol, expression is decreased for ERK2, but the protein level is normal. In the same group, KRAS expression is comparable to the controls, but protein levels are greatly increased. What is the explanation for this disconnect? In figure 9, are statistical tests only performed for the last treatment point (day 21)? If so, this must be stated. Other time points are likely significant if also considered. In the figure legend, I hope that p<0.5 is a typo meant to be p<0.05. The former significance cutoff is not stringent enough. In figure 11, what are the statistical significances for? And what statistical test was employed? Are you saying that all of the organs from a treatment group are significantly different than their corresponding values in the vehicle group? What about comparisons between treatment groups? Such analyses may require a multiple comparisons post hoc correction be used in the statistical analysis. Numerous typos throughout including, but not limited to, T750M and L858M (page 3). There are also red underlines in the text for figure 14 that should be removed. Antibodies used in western blots must be noted with their source and catalog number since they can vary widely. Source data should include the individual replicates for each experiment in addition to just the mean ± SEM\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "347134",
"date": "03 Jan 2025",
"name": "Chandan Shivamallu",
"expertise": [
"Reviewer Expertise Microbiology",
"Cancer Biology",
"Computational Biology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript presents an innovative approach to repurpose acenocoumarol and silodosin as allosteric inhibitors targeting EGFR for non-small-cell lung cancer (NSCLC). The combination of computational tools, in vitro analyses, and in vivo xenograft studies offers a vigorous frame for evaluating the potential of these drugs in a therapeutic context. The repurposing of clinically approved drugs as EGFR allosteric inhibitors provides a promising pathway to overcome drug resistance in NSCLC. This approach leverages known safety profiles, accelerating clinical translation. For this, the comprehensive methodology applied such as in silico, in vitro and in vivo is commendable. The molecular docking and dynamic studies are detailed and provide strong evidence of binding affinity for the EGFR allosteric site. Cytotoxicity, apoptosis, cell cycle arrest, and gene expression studies are systematically performed, showcasing the drugs’ mechanisms of action. The inclusion of tumor regression and histopathological analysis strengthens the translational relevance of the findings. The significant findings include both acenocoumarol and silodosin demonstrated effective inhibition of KRAS and ERK2, key players in EGFR signaling. The observed upregulation of caspase-3 and tumor growth inhibition validates the anti-NSCLC activity of these drugs. Further, the manuscript adheres to ethical guidelines, and all experimental procedures are well-documented, reflecting the integrity of the research. The findings in this work warrant publishing of this manuscript, however few suggestions for improvement are 1) While the data are extensive, certain figures and tables lack concise labeling and clarity, which could hinder understanding for readers who are unfamiliar with the subject. 2) In the discussion part, readers could benefit from a more detailed comparison with existing EGFR inhibitors, emphasizing the advantages of acenocoumarol and silodosin in terms of efficacy, selectivity, and safety. 3) Although the study concludes with a call for clinical trials, the discussion could elaborate on the specific challenges, such as pharmacokinetics and potential side effects, that need addressing for these drugs. 4) Minor grammatical inconsistencies and redundancies could be refined to enhance the readability and professionalism of the manuscript.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1398
|
https://f1000research.com/articles/13-1397/v1
|
21 Nov 24
|
{
"type": "Research Article",
"title": "Comparison of the severity of urinary tract infections between Metformin and SGL2 Inhibitors among Iraqi Type 2 Diabetics.",
"authors": [
"Diana Noori Hussien",
"Samara Mowafaq Ali",
"Samara Mowafaq Ali"
],
"abstract": "Background Many antidiabetic medications with distinct modes of action are available, The sodium glucose cotransporter-2 (SGLT-2) inhibitors are among the most recent oral antihyperglycemic medications. The American Diabetes Association recommends metformin, a biguanide medication, as the first option for oral control of type 2 diabetes because it has demonstrated promise in this regard.\n\nAim of the study To evaluate and compare the effects of metformin and SGLT-2 inhibitors on general urine parameters in T2DM patients from Iraq.\n\nMethod a prospective cohort study where 101 adult patients of both sexes aged under 70 years and newly diagnosed with T2DM, patients were divided into two groups, Metformin group (n=52), where metformin was prescribed as monotherapy by the clinician and SGLT-2 inhibitors group (n=49) where either dapagliflozin or empagliflozin were prescribed by the clinician, general urine examination was done for each patient in the first contact and after 12 weeks of treatment.\n\nResults The mean age was 57±9 years for the metformin group and 54±9 years for the SGLT-2 inhibitors group. There was no significant difference in leukocytes, erythrocytes, or epithelial cell counts between the metformin group and the SGLT2 inhibitor group before and after 12 weeks of treatment. There was a significant difference (p-value =0.043) in leukocytes and a non-significant difference in erythrocytes and epithelial cell counts before and after treatment in the SGLT-2 inhibitors group.\n\nConclusions Diabetic patients on SGLT-2 inhibitors treatment demonstrated higher leukocyte count than metformin group patients, an indicator and predictor for higher susceptibility to urinary tract infections.",
"keywords": [
"Urinary Tract Infection",
"Metformin",
"SGLT-2 inhibitors",
"diabetes mellitus."
],
"content": "Introduction\n\nDiabetes mellitus type 2 (T2DM) is linked to a high rate of death and morbidity, and it may harm the patient’s cardiovascular, renal, and neurological systems.1 One of the main risk factors for type 2 diabetes is a family history of the disease. It is characterized by gradual dysfunction of β-cells; numerous studies have employed C peptide levels as a biomarker of β-cell function.2 Patients with coronary artery disease have more health issues as a result of insulin resistance, which is the primary cause of type 2 diabetes.3 Diabetes mellitus type 2 frequently results in diabetic nephropathy. Urine and plasma contain neutrophil gelatinase-associated lipocalin (NGAL), which is detectable beginning two to four hours following a kidney injury. When GFR decreased, serum NGAL rose noticeably. Regarding type 2 diabetes mellitus, serum NGAL may be a prognostic sign for the early identification of diabetic nephropathy.4 In the general population, diabetes mellitus type II (DM) is one of the main causes of osteoporosis.5 Longer diabetes duration was associated with a higher risk of UTI rather than glycemic control (HbA1C). Women receiving pharmaceutical treatment for diabetes were primarily at higher risk, indicating a correlation between the severity of diabetes and UTI risk. The most frequently isolated organism in all women, including young women, was E. coli.6 Among female diabetics with problems of neuropathy, nephropathy, and retinopathy, the prevalence of asymptomatic pyuria has increased. As diabetic microangiopathy worsens, the prevalence of asymptomatic pyuria rises with the increasing period of having diabetes.7 Medication and lifestyle modifications are two methods for treating type 2 diabetes. The American Diabetes Association8 recommends that the biguanide medication metformin be used as the primary option for oral therapy of type 2 diabetes because it has demonstrated promise. Weight loss, vascular protection, and glucose metabolism are all positively impacted by metformin.9 Patients with type 2 diabetes (T2DM) may have considerable differences in their glycemic control and adiposity indicators due to a variety of factors, including metformin dosages and treatment adherence. Elevating the metformin dose did not correlate with body fat percentage or insulin resistance.10 Dapagliflozin is a popular oral antidiabetic medication that selectively and reversibly inhibits the sodium-glucose co-transporter-2 (SGLT-2). It increases urine glucose excretion, which can dramatically reduce hyperglycemia without affecting the function of the pancreatic β cell. Compared to the control group, dapagliflozin improves hemoglobin concentration and corrects anemia in patients with heart failure and CKD.11 SGLT-2 inhibitors provide bacteria with a substrate to feed on since they increase the amount of glucose in the urinary system. As a result, they have already been connected to genitourinary tract infections.12 The current study aims to evaluate and compare the effects of metformin and SGLT-2 inhibitors on general urine parameters in T2DM patients from Iraq.\n\n\nMethods\n\nIn a prospective study where 101 adult patients of both sexes aged under 70 years and newly diagnosed with T2DM based on the International Expert Committee criteria,13 patients were recruited and called weekly from a single private clinician record who gave informed consent to access the weekly patient archives for 2 months. The recruited patients were then divided into two groups: the Metformin group (n=52), where metformin was prescribed as monotherapy by the clinician, and the SGLT-2 inhibitors group (n=49) where either dapagliflozin or empagliflozin were prescribed by the clinician, Each patient was invited to a private laboratory where sociodemographic data (age, education level, social status, and smoking status) and clinical data were collected during the face-to-face interviews with the patients. A microscopic general urine examination was then done for each patient on their first contact and after 12 weeks of treatment.\n\nThe study was conducted in cooperation with a single private internist clinic and a single private laboratory in Baghdad, Iraq. The patients were recruited and did their first general urine examination in the period between the 1st of January 2023 and the 1st of March 2023, All patients underwent their second test before the 1st of May 2023, and all patients and other private parties provided their written and informed consent to participate in the study.\n\nInclusion criteria\n\nAdult Patients of both sexes aged under 70 years old, newly diagnosed with T2DM,13 taking either metformin monotherapy or SGLT-2 inhibitors (Dapagliflozin or Empagliflozin).\n\nExclusion criteria\n\nPatients who refused to participate in the study, patients with ongoing acute or chronic kidney diseases, and patients with ongoing urinary tract infections.\n\nEach patient was provided 15-30 ml of clean-catch midstream urine, the urine specimen was then prepared and examined under the High Power Field of the light microscope (Olympus BX51 Microscope, Olympus Corporation®, Japan) to count the cells and provide the result of cellular microscopic examination.\n\nEach patient underwent two microscopic general urine examinations separated by 12 weeks of continuous diabetes treatment, data on the Erythrocyte count, Leukocyte count, and epithelial cell count was then obtained in the Cell/HPF unit to evaluate and compare the effect of both metformin and SGLT-2 inhibitors on these urinary parameters.\n\nEach eligible patient completed the research tool in writing and completed the consent form. The following formula was utilized to determine the sample size14: n=Z1−α22σ2d2\n\nIn this case, d indicates the precision of the quantitative variable estimate, n is the sample size, α is the first type, Z is the table-based normal distribution index that is taken into account at 5% type-one error (P<0.05), and σ stands for the small variable variance.15 A first type error in this study has values of 0.05, 96.3, 7.38, and 0.99, correspondingly for z, σ, and d. XXX were taken into consideration as the sample size and were included in the data analysis after accounting for the 10% non-response.16 For every region in the nation, a sample size of XXX was determined with a design effect of 2, 80% statistical power with a two-sided test, and α = 0.05 to detect a 10% decrease. It was assumed that 30% of people had an irregular legal status at time 1 (the current study) and 20% at time 2 (the subsequent study round).17\n\nEthical considerations\n\nThe study was approved by the Institutional Review Board (IRB) in the College of Medicine/University of Baghdad (Approval no. 03-11 on 31st of December 2023), the ethical approval for the current study was uploaded to the Zenodo: Ethical approval and reporting guidelines. https://doi.org/10.5281/zenodo.14037291.18\n\nThis project contains the following file: (Ethical approval.jpg).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThe obtained data were entered, coded, displayed, and examined using a computer utilizing the IBM SPSS-29 statistical package (IBM Statistical Packages for Social Sciences, version 29, Chicago, IL, USA) that was made accessible as a database software program. Simple metrics of frequency, percentage, mean, standard deviation, and range (minimum-maximum values) were used to present the data.19 The Students-t test was used to determine the significance of the difference between two independent means (quantitative data). When evaluating the significance of differences in percentages (qualitative data), the Pearson Chi-square test (χ2-test) was employed, along with Yate’s adjustment or the Fisher Exact test if necessary. The P value was considered statistically significant if it was equal to or less than 0.05.20\n\n\nResults\n\nThe study included 101 patients with type 2 diabetes mellitus; 52 were receiving metformin, and 49 were receiving either dapagliflozin or empagliflozin. The mean age of the patients was 57±9 for metformin and 54±9 for SGLT2 inhibitors; 63.5% were illiterate, 94.2% of the metformin group and 93.9% of SGLT2 inhibitor group were married, 78.8% of the metformin group and 81.6% of SGLT2 inhibitor group were non-smokers, and 53.8% of metformin group and 57.1% of SGLT2 inhibitor group were hypertensive ( Table 1).\n\n* Significant difference between percentages using Pearson Chi-square test (χ2-test) at 0.05 level.\n\n# Significant difference between two independent means using Students-t-test at 0.05 level.\n\nThere was no significant difference (p-value > 0.05) in leukocytes, erythrocytes, or epithelial cell counts before and after treatment between the metformin group and the SGLT2 inhibitor group, as shown in Table 2.\n\n* Significant difference between percentages using Pearson Chi-square test (χ2-test) at 0.05 level.\n\nThere was no significant difference (p-value>0.05) in leukocytes, erythrocytes, or epithelial cell counts before and after treatment in the metformin group, as shown in Table 3.\n\n* Significant difference between percentages using Pearson Chi-square test (χ2-test) at 0.05 level.\n\nThere was a significant difference (p-value = 0.026) in leukocytes and a non-significant difference in erythrocytes and epithelial cell counts before and after treatment in the SGLT2 inhibitor group ( Table 4).\n\n* Significant difference between percentages using Pearson Chi-square test (c2-test) at 0.05 level.\n\nThere was a significant difference (p-value = 0.043) in leukocytes and a non-significant difference in erythrocytes and epithelial cell counts before and after treatment in the dapagliflozin group, as shown in Table 5.\n\n* Significant difference between percentages using Pearson Chi-square test (χ2-test) at 0.05 level.\n\nThere was no significant difference (p-value> 0.05) in leukocytes, erythrocytes, or epithelial cell counts before and after treatment in the empagliflozin group, as shown in Table 6.\n\n* Significant difference between percentages using Pearson Chi-square test (χ2-test) at 0.05 level.\n\n\nDiscussion\n\nOur study’s findings show that the metformin group and the SGLT2 inhibitor group did not significantly differ in their counts of leukocytes, erythrocytes, or epithelial cells before or after treatment, as shown in Table 2. In comparison to other antidiabetic medications, the use of SGLT2 inhibitors is not linked to an increased incidence of UTIs, according to the findings of a study conducted by Wajd Alkabbani in 2022 to evaluate the risk of UTIs related to SGLT2 inhibitors in type 2 diabetes.21 Additionally, Table 3 shows no statistically significant difference in the metformin group’s counts of leukocytes, erythrocytes, or epithelial cells before and after treatment. In a study published in 2022, Fu-Shun Yen compared the morbidity and mortality linked to sepsis and UTI in patients with diabetes between metformin users and nonusers. The findings indicated that among patients with type 2 diabetes, metformin use was not significantly associated with a lower risk of sepsis, recurrent UTI, or UTI. Compared to metformin nonuse, it was linked to a decreased risk of death from a UTI or sepsis.22 In contrast, the SGLT2 inhibitor group’s data revealed a non-significant change in the numbers of erythrocytes and epithelial cells before and after treatment but a significant difference in leukocytes ( Tables 4,5). According to research by Zhigui Zheng, they were published in 2023, dapagliflozin 10 mg/day for a treatment period longer than 24 weeks was associated with a significantly higher risk of urinary tract infection (UTI) than placebo or other active treatments. As a result, patients with type 2 diabetes mellitus should carefully consider the risk of UTI before beginning high-dose, long-term dapagliflozin therapy or adding it on top of existing treatment.23 However, when one of the four SGLT2 inhibitors—dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin is used in a meta-analysis study to estimate the association between the use of these drugs and the risk of UTI, the results indicate that dapagliflozin appears to independently increase the risk of UTI, though the mechanism underlying this intra-class variation in risk is unclear.24 Another study conducted in 2013 by Kristina M. Johnsson revealed a small increase in the incidence of urinary tract infection when type 2 diabetes is treated with once-daily dapagliflozin 5 or 10 mg. Most infections were mild to severe and controlled clinically.25 Our findings about empagliflozin indicated that there was no discernible change in the counts of leukocytes, erythrocytes, or epithelial cells in the group receiving therapy before and after the medication (see Table 6). According to the results of a study conducted in 2024 by Cristina Rebordosa, patients with type 2 diabetes who started taking empagliflozin compared to those who started taking a dipeptidyl peptidase-4 (DPP-4) inhibitor had higher risks of DKA and GI and lower risks of ALI, AKI, CKD, and severe UTI complications when using empagliflozin.26 However, results from a study conducted in 2021 by Arbinda Pokhare on type 2 diabetes patients using empagliflozin revealed that UTIs (17.8%), nasopharyngitis (11.9%), and hypoglycemia (10.71%) were the most often reported side effects of the medication.27 According to Chunmei Xu’s study, SGLT2i was found to have comparable anti-hyperglycemic efficacy to metformin monotherapy, including reducing blood glucose and HbA1c without significantly raising the incidence of UTIs. It also significantly reduced cardiovascular risk factors. However, a study by Mustafa Tanriverdi28 revealed that glucosuria and SGLT-2i use predicted UTI in T2D patients. It also suggested that urine culture is crucial when determining the kind and mode of administration of antibacterial treatment, particularly for patients on SGLT-2i treatment.29 In contrast to individuals on non-SGLT2 inhibitors, patients taking dapagliflozin and empagliflozin had a higher incidence of UTIs, according to a study by Uitracul. Furthermore, when treated with SGLT2 inhibitors, patients who were older and female had a considerably higher incidence of UTI, but patients who had permanent jobs had a reduced risk.30 Among 17 trials evaluating dapagliflozin, 499 events suggestive of UTIs were recorded in 7145 participants (raw event rate 7.0%). A meta-analysis of these trials revealed that, in comparison to the control, dapagliflozin was linked to an increased risk of events that could be indicative of UTIs.31 Furthermore, SGLT2 inhibitor-induced glucosuria probably contributes to an increased risk of genital infections and urinary tract infections to a lesser degree. Treatment with SGLT2 inhibitors does not raise the risk of upper UTIs (pyelonephritis). Furthermore, SGLT2 inhibitors have been linked to an increase in benign urine symptoms brought on by osmotic diuresis, such as an increase in urine output. This might have also made it more likely that patients on SGLT2 inhibitors would have been diagnosed with infections.32\n\nSuperior evidence could be provided by studying more urinary parameters on a larger sample of T2DM Iraqi patients taking metformin and SGLT-2 Inhibitors and by extending the monitoring period to evaluate the risk and incidence of urinary tract infections among these patients in controlled trials.\n\n\nConclusions\n\nDiabetic patients on SGLT-2 inhibitors treatment demonstrated higher leukocyte count than metformin group patients, an indicator and predictor for higher susceptibility to urinary tract infections.\n\nThe study was approved by the Institutional Review Board (IRB) in the College of Medicine/University of Baghdad (Approval no. 03-11 on 31st of December 2023), the ethical approval for the current study was uploaded to the Zenodo: Ethical approval and reporting guidelines. https://doi.org/10.5281/zenodo.14037291.18\n\nThis project contains the following file:\n\n• (Ethical approval.jpg).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nAll patients and other private parties provided written and informed consent to participate in the study.\n\n\nAuthors’ contribution\n\nDNH contributed to conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, validation, visualization, and writing-original draft preparation. SMA contributed to conceptualization, data curation, investigation, methodology, project administration, resources, supervision, writing – review & editing.",
"appendix": "Data availability\n\nZenodo: “Impact of Metformin vs SGLT-2i on urinary parameters (Latest Version)”, https://doi.org/10.5281/zenodo.14055980.33\n\nThis project contains the following underlying data file:\n\n• (Data: Latest version.xlsx).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nSTROBE criteria for cohort studies was used as reporting criteria for the current study. The complete filled-in reporting guideline document for the current study was uploaded to Zenodo: Ethical Approval and Reporting Guidelines. https://doi.org/10.5281/zenodo.14037291.18\n\nThis project contains the following file:\n\n• (Reporting guidelines.doc).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0) (https://creativecommons.org/licenses/by/4.0/).\n\n\nReferences\n\nHealth UDo, Services H: National Diabetes Information Clearinghouse (NDIC). National diabetes statistics.2011.\n\nAbed B: The Relationship between Family History and C-peptide Level in Type2 Diabetic Patients. Journal of the Faculty of Medicine Baghdad. 2013; 55: 258–264. Publisher Full Text\n\nArif M, Rasheed M, Ismaeel A: Study some biochemical parameters in patients with Coronary artery disease with and without Type 2 diabetesStudy of some Biochemical Parameters in Patients with Coronary Artery Disease with and without Type 2 Diabete. Journal of the Faculty of Medicine Baghdad. 2024; 66: 51–57. Publisher Full Text\n\nAllawi A, Kahdem A, Nada SZ, et al.: Neutrophil gelatinase associated lipocalin (NGAL) in early detection of nephropathy in type 2 diabetic Iraqi patients. Journal of the Faculty of Medicine, Baghdad. 2017; 59: 74–78. Publisher Full Text\n\nAziz ZSA, Numan S, Al-khalisy MH: Evaluation of the effect of type II diabetes mellitus on bone mineral density of upper and lower limbs by dual-energy X-ray absorptiometry. Journal of the Faculty of Medicine Baghdad. 2023; 65(1): 27–33. Publisher Full Text\n\nAyoub NS, Abdallah K, AL-Khazraji SK: Bacterial profile of urinary tract infections in Diabetic postmenopausal women. Journal of the Faculty of Medicine Baghdad. 2014; 56(1): 79–84. Publisher Full Text\n\nNasir HA: Asymptomatic pyuria in diabetic females. Journal of the Faculty of Medicine Baghdad. 2006; 48(3): 274–276. Publisher Full Text\n\nBergenstal RM, Wysham C, Macconell L, et al.: Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010; 376(9739): 431–439. PubMed Abstract | Publisher Full Text\n\nEffect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352(9131): 854–865. PubMed Abstract | Publisher Full Text\n\nAbdulrahman Z, Atrakji M, Al-Maliky A, et al.: Influence of Metformin Dose and Treatment Adherence on Glycemic Control, Zainab S. Abdulrahman Adiposity, and Cardiovascular Risk Markers in Iraqi Patients with T2DM. Journal of the Faculty of Medicine Baghdad. 2023; 64: 218. Publisher Full Text\n\nObeed AA, AL-Kinani TA, AL-Qadhi H: Effect of dapagliflozin on hemoglobin level in heart failure patients with chronic kidney disease and/or diabetes. Journal of the Faculty of Medicine Baghdad. 2022; 64(4): 203–207.\n\nGeerlings SE, Meiland R, Hoepelman AI: Pathogenesis of bacteriuria in women with diabetes mellitus. International Journal of Antimicrobial Agents. 2002; 19(6): 539–545. Publisher Full Text\n\nInternational Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009; 32(7): 1327–1334. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoore DS, McCabe GP: Introduction to the practice of statistics. WH Freeman/Times Books/Henry Holt & Co; 1989.\n\nDawson B, Trapp RG: Basic & clinical biostatistics. Basic & clinical biostatistics.2004; 438.\n\nJavaheri Tehrani F, Nikpour S, Haji Kazemi EA, et al.: The effect of education based on health belief model on health beliefs of women with urinary tract infection. International Journal of Community-Based Nursing and Midwifery. 2014; 2(1): 2–11. PubMed Abstract\n\nPham PN, Johnston LG, Keegan K, et al.: Innovative Strategies for Remotely Sampling Hard-to-Reach Populations: Assessing Phone Versus Internet Respondent-Driven Sampling Approaches Among Venezuelan Refugees and Migrants in Colombia. American Journal of Epidemiology. 2023; 192(10): 1613–1623. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHussien DN: Ethical Approval and reporting guidelines. 1.0 ed2024. Zenodo.\n\nCelentano DD, Szklo M, Farag Y: Gordis Epidemiology E-Book: Gordis Epidemiology E-Book. Elsevier Health Sciences; 2023.\n\nDaniel WW: Biostatistics: a foundation for analysis in the health sciences. Wiley; 1978.\n\nAlkabbani W, Zongo A, Minhas-Sandhu JK, et al.: Sodium-Glucose Cotransporter-2 Inhibitors and Urinary Tract Infections: A Propensity Score-matched Population-based Cohort Study. Canadian Journal of Diabetes. 2022; 46(4): 392–403.e13. PubMed Abstract | Publisher Full Text\n\nYen FS, Wei JC, Shih YH, et al.: Role of Metformin in Morbidity and Mortality Associated with Urinary Tract Infections in Patients with Type 2 Diabetes. Journal of Personalized Medicine. 2022; 12(5). PubMed Abstract | Publisher Full Text | Free Full Text\n\nZheng Z, He D, Chen J, et al.: Risk of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Treated with Dapagliflozin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clinical Drug Investigation. 2023; 43(4): 209–225. PubMed Abstract | Publisher Full Text\n\nDonnan JR, Grandy CA, Chibrikov E, et al.: Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019; 9(1): e022577. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJohnsson KM, Ptaszynska A, Schmitz B, et al.: Urinary tract infections in patients with diabetes treated with dapagliflozin. Journal of Diabetes and Its Complications. 2013; 27(5): 473–478. Publisher Full Text\n\nRebordosa C, Thomsen RW, Tave AK, et al.: Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts. Diabetes, Obesity and Metabolism. 2024; 26(4): 1291–1304. PubMed Abstract | Publisher Full Text\n\nPokharel A, Kc S, Thapa P, et al.: The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease. Cureus. 2021; 13(7): e16687. PubMed Abstract | Publisher Full Text\n\nXu C, He L, Zhang J, et al.: The Cardiovascular Benefits and Infections Risk of SGLT2i versus Metformin in Type 2 Diabetes: A Systemic Review and Meta-Analysis. Metabolites. 2022; 12(10). PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanrıverdi M, Baştemir M, Demirbakan H, et al.: Association of SGLT-2 inhibitors with bacterial urinary tract infection in type 2 diabetes. BMC Endocrine Disorders. 2023; 23(1): 211. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUitrakul S, Aksonnam K, Srivichai P, et al.: The Incidence and Risk Factors of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Using SGLT2 Inhibitors: A Real-World Observational Study. Medicines (Basel). 2022; 9(12). Publisher Full Text\n\nLiu J, Li L, Li S, et al.: Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Scientific Reports. 2017; 7(1): 2824. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeerlings S, Fonseca V, Castro-Diaz D, et al.: Genital and urinary tract infections in diabetes: impact of pharmacologically-induced glucosuria. Diabetes Research and Clinical Practice. 2014; 103(3): 373–381. PubMed Abstract | Publisher Full Text\n\nHussien DN: Impact of Metformin vs SGLT-2i on urinary parameters (Latest Version). 1.0 ed.2024. Zenodo."
}
|
[
{
"id": "354138",
"date": "17 Jan 2025",
"name": "Mahesh M. Umapathysivam",
"expertise": [
"Reviewer Expertise Type 2 Diabetes",
"Genetics",
"SGLT2i DKA",
"inpatient glucose management",
"incretin hormones"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of Context:\nMultiple agents are available for the treatment of type 2 diabetes. Current American diabetes association guidelines suggest initial treatment with metformin and intensification with SGLT2i or GLP-1RA as preferred second line agents depending on patient characteristics. SGLT2i reduce glycaemia by increasing urinary glucose an effect that has been associated with candidiasis but whilst large cardiovascular outcome trials have not demonstrated increased rates of UTI (these should be referenced), this study design can miss safety signals.\nThis study aimed to contribute to the literature in the field on this complication by prospectively following patients with either metformin or SGLT2 monotherapy and then examining a surrogate for urinary tract infection - number of leucocytes per high power field on microscopy at base line and then at 12 weeks. Notably this end point may be limited due to increased urinary volume with SGLT2i treatment or increased leukocyte number in setting of non-bacterial infection e.g. candidiasis. The study reports the number of leucocytes in various categories and other cell populations before and after therapy with metformin and SGLT2i. There was no difference when groups were compared but there was an increase in urinary leucocytosis after 12 weeks of SGLT2i compared to baseline. In the text it does not explicitly state at any point state if this is increased or decreased or the magnitude of change. . The results report.\nI have not recommended for indexing in current state as there is inconsistency between results and conclusion and this need to be addressed prior to consideration of indexing.\nThe following specific suggestions are offered to strengthen the article;\n\nTitle: Use people first language i.e. “diabetic” is not appropriate it should be “person with diabetes” or similar. The title should reflect what was measured i.e. urinary tract infections were not measured urinary leucocytosis was measured.\nAbstract:\nThis should follow STROBE format more closely. Remove “because it has demonstrated promise in this regard”. State T2DM in full then abbreviate. Be clearer in the language around the results and state direction of effect and magnitude. Conclusion is not consistent with results – The results state “There was no significant difference in leukocytes, erythrocytes, or epithelial cell counts between the metformin group and the SGLT2 inhibitor group before and after 12 weeks of treatment” whilst conclusion states “Diabetic patients on SGLT-2 inhibitors treatment demonstrated higher leukocyte count than metformin group patient”. Please check capitalisation throughout.\nIntroduction:\nRemove content that does not relate to the proposed study – e.g. discussion of relation between diabetes and osteoporosis and discussion of NGAL. This section should focus on setting up the justification for the study. Reference 12 for association between SGLT2i and infection is incorrect. Please review. Samples size section is incomplete with multiple areas marked XXX.\nMethods:\nEthics: Patients completed written informed consent but study states 63.5% were illiterate please clarify.\nIt would be helpful to know renal function and Hba1c at baseline and at 12 weeks if possible. It would be helpful to know why individuals were treated with SGLT2i monotherapy rather than metformin. Are these populations very different? Ascertainment bias should also be included as a limitation. A definition of a “positive test” need to be provided.\nResults:\nMore description of results is required. It would help the reader to know the direction of effect for significant results and the magnitude of the difference. Presentation of the average number of leukocytes with comparison of students T test would be useful I am unsure what “it was assumed that 30% of people had an irregular legal status at time 1 and 20% at time 2” means\nConclusion:\nThere is conflict throughout between the reporting of results and interpretation. To my reading there is no statistical difference between metformin group and SGLT2i group. There is an increase statistically significant increase in leukocytes after initiation of SLT2i compared to before. This should form the basis of discussion.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1397
|
https://f1000research.com/articles/13-303/v1
|
19 Apr 24
|
{
"type": "Research Article",
"title": "In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1",
"authors": [
"Margot Paco-Chipana",
"Karel Mena-Ulecia",
"Yoan Hidalgo Rosa",
"Maria Isabel Herrera Valdivida",
"Luis Daniel Goyzueta-Mamani",
"Berly Cardenas-Pillco",
"Miguel Angel Chavez-Fumagalli",
"Haruna Luz Barazorda-Ccahuana",
"Margot Paco-Chipana",
"Karel Mena-Ulecia",
"Yoan Hidalgo Rosa",
"Maria Isabel Herrera Valdivida",
"Luis Daniel Goyzueta-Mamani",
"Berly Cardenas-Pillco",
"Miguel Angel Chavez-Fumagalli"
],
"abstract": "Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1.\n\nMethods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA).\n\nResults This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid.\n\nConclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.",
"keywords": [
"Echinococcus granulosus",
"EgFABP1",
"fatty acids",
"gene ontology",
"quantum mechanics",
"molecular dynamics simulation",
"MM/GBSA"
],
"content": "Introduction\n\nParasitic nematodes are responsible for significant human suffering, with an astounding 1.5 billion individuals suffering from helminth infections brought on by soil. They infect people, injure cattle, and reduce food production, which results in morbidity and mortality on a global scale.1 The cestode species of the genus Echinococcus,2–4 currently divided into the species Echinococcus granulosus sensu lato species complex, Echinococcus multilocularis, Echinococcus shiquicus, Echinococcus vogeli, and Echinococcus oligarthra, cause echinococcosis, also known as hydatid disease, and it is estimated that over a million people are afflicted worldwide.5 While the disease manifests clinically as cystic (CE), alveolar (AE), and neotropical (NE) echinococcosis, CE is the most common worldwide, producing substantial morbidity and relative mortality among human populations and is caused by E. granulosus complex.6\n\nBenzimidazoles (BMZ), specifically albendazole and mebendazole when albendazole is not well tolerated, are the only medications now available against CE and AE in clinical settings. In CE, BMZ is additionally used to stop recurrence caused by protoscolece leakage following surgery or percutaneous treatment, either by itself or in combination.7 Much of the parasites’ success is due to their ability to disguise themselves from host immune defenses. However, despite the importance of these organisms to human and animal health, little is understood about the molecular mechanisms that underpin these stealth processes. Increasing our knowledge of how parasitic nematodes influence the immune system has tremendous potential to guide the development of new therapies for immunological dysregulation.8\n\nThe acquisition, storage, and transportation of lipids for the formation of hydatid cysts is made possible in this situation by the E. granulosus fatty-acid-binding protein 1 (EgFABP1). To promote the uptake of lipids, the ligand-binding association with EgFABP1 causes a conformational change in the protein structure. This modification of the interaction mechanism with membranes is also feasible,9 which has made fatty acids (FAs) interesting drug targets. These are classified as saturated fatty acids (SFAs, without double bonds) and unsaturated fatty acids (UFAs, with the presence of double bonds). Also, UFAs are classified as monounsaturated fatty acids (MUFAs) which have only one double bond, and polyunsaturated fatty acids (PUFAs) which have two or more double bonds.10\n\nIt has been demonstrated that PUFAs have anti-inflammatory and antibacterial effects, including their effectiveness in protecting against several parasite-related disorders.11 Jae-Won Choi et al.12 suggested that (ω)-3 PUFAs could be a potential therapeutic candidate for preventing diseases such as toxoplasmosis and other parasitic infections by intracellular protozoa. Moreover, Muturi K.N. et al.13 has shown that a diet of (ω)-6 and (ω)-3 PUFAs is important in immunity against nematode parasites. However, according to Katdare Aakash et al.14 there are many studies of fatty acids as therapeutic additives, but more studies are still required to confirm these as unique therapeutic agents. Because of this, there is a need for greater research to determine how effective certain FAs are at preventing parasite infections caused by E. granulosus.\n\nIn this study, we evaluated the binding free energy of fatty acids against EgFABP1 using molecular mechanics generalized born surface area (MM/GBSA) methodology. Additionally, EgFABP1 analysis was performed regarding phylogeny and gene ontology (GO) enrichment analysis and protein-protein interaction network analysis. The study also delved into the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of various fatty acids, coupled with an examination of their chemical reactivity using quantum mechanics. Finally, an in-depth exploration was undertaken through all-atom molecular dynamics simulations to analyze the binding free energy of the EgFABP1 complex.\n\n\nComputational details\n\nThe FASTA sequence of the Echinococcus granulosus fatty acid-binding protein 1 (EgFABP1) protein from Echinococcus granulosus (ID: Q02970) was retrieved from the UniProt database (http://www.uniprot.org/),15 and subjected to the Blastp tool,16 followed by a sequence similarity search performed on E. granulosus (taxid:6210) within the non-redundant protein sequence database. To investigate the evolutionary relationship of EgFABP1 proteins, the retrieved sequences were uploaded in MegaX software and aligned using ClustalW.17 Utilizing the neighbor-joining technique utilized by iTOL, the resulting multiple sequence alignments was used to reconstruct and show a distance-based phylogenetic tree.18 Also, the EgFABP1-related sequences were uploaded into the Cytoscape platform,19 where the plugin StringApp19 was used to retrieve and extend the molecular network information from the STRING database20 and the plugin cytoHubba was used to score and rank the nodes according to network properties, affording to the Maximal Clique Centrality (MCC) topological analysis method.21 The default parameters of Cytoscape were used to show the network; node size and color were manually changed according to the scores obtained from the MCC analysis. Finally, StringApp was also used to retrieve functional enrichment for Gene Ontology (GO) terms, regarding Biological Processes (BP), Molecular Functions (MF), and Cellular Components (CC), while the results were expressed in bubble plots employing the SRplot online platform (http://www.bioinformatics.com.cn/srplot).\n\nIn this work, fourteen FAs were selected from PubChem database.22 The PubChem CID access code and chemical structure are described in Table 1. The geometries of these compounds were optimized using B3LYP/6-311++g(d,p) basis set level, implemented in ORCA software version 4.1.2.23,24 The ground-state was verified by counting the imaginary frequencies of each compound.\n\nThe FAs optimized geometries were used for global and local reactivity descriptors calculation; the methodology is described below.\n\nGlobal reactivity descriptors\n\nGlobal reactivity descriptors are derived from conceptual Density Functional Theory (DFT),25 this type of analysis allows us to understand the relationships among structure, stability and reactivity.26 The global reactivity descriptors were calculated by the mean Koopmans’ theorem, which considers the HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital) energy orbitals (Table 2).\n\na HOMO orbital energy.\n\nb LUMO orbital energy.\n\nLocal reactivity descriptors: Fukui function\n\nElectrophilic, nucleophilic and radical attacks were calculated using Fukui functions.35 The optimized geometries were selected compounds, and single point energy calculation was performed on the neutral, positive and negatively charged molecule using B3LYP/6-311++g(d,p) basis set implemented in ORCA software version 4.1.2.23,24 The Fukui functions were calculated using Multiwfn36 according to the following equations:\n\nNucleophilic attack:\n\nElectrophilic attack:\n\nRadical attack:\n\nWhere ρN is the electron density at a point r in space around the molecule. The N corresponds to the number of electrons in the molecule. N+1 corresponds to an anion with an electron added to the LUMO of the neutral molecule. N−1 is the cation with an electron removed from the HOMO of the neutral.\n\nThe Molecular Weight (MW), Hydrogen Bonds (nHA, nHB), Polar Surface Area (PSA), Dissociation Constant (pKa), the logarithm of the molar solubility in water (logS), n-octanol/water partition coefficient (logP), n-octanol/buffer solution distribution coefficient at pH = 7.4 (logD7.4), and ADMET pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity) were performed on the ADMETlab 2.0 online platform (https://admetmesh.scbdd.com/). The prediction of pKa values was obtained by MolGpKa web server (https://xundrug.cn/molgpka).\n\nThe protein structure of Echinococcus granulosus fatty-acid-binding protein I (EgFABP1) was downloaded from the Protein Data Bank37,38 (https://www.rcsb.org) under access code PDB ID: 1O8V. This protein presents a hydroxylated cysteine (CSO63) that was considered in this work. We defined the AMBER99SB-ILDN force field parameters of the CSO63 and fourteen FAs in the ACPYPE39 server online (https://www.bio2byte.be/login/?next=/acpype/). Finally, the water molecules present in the crystal structure were removed.\n\nThe coupling systems were solved in the DockThor server40,41 (https://dockthor.lncc.br/v2) with a grid dimension of 5 × -7 × 10, the genetic algorithm settings with number of evaluations = 1000000, population size = 750, and number of runs = 24.\n\nThe molecular dynamics (MD) simulation was carried out using GROMACS v.2020.642 with the AMBER99SB-ILDN force field. Fifteen MD simulations, EgFABP1 without ligand and EgFABP1 coupled to fourteen FAs was considered. The topologies were prepared considering a cubic box of 1 nm from the edge of the box to the protein surface. The TIP3P water model was used for the solvation of the different systems. 200000 energy minimization steps were settled with the steep-descent algorithm. Equilibrium dynamics simulations in the canonical ensemble at constant volume and the production simulation in the isobaric-isothermal at constant pressure (1 bar of reference pressure with Parrinello-Rahman barostat) were applied. The calculation time in isobaric-isothermal ensemble (NPT) was 200 ns. In both MD simulations, the V-rescale thermostat regulated the temperature at 309.65 K. The analysis of the MD was carried out with the Gromacs tools and plotted in the Gnuplot v. 4.543 software. Additionally, hydrophobic interactions between FAs and EgFABP1 were analyzed using the PLIP (Protein-Ligand Interaction Profiler) server.44 The graphical visualizations were evaluated in the VMD (Visual Molecular Dynamics)45 and UCSF Chimera v.1.1546 software.\n\nThe binding free energy from each coupling system (EgFABP1-FAs) was calculated by Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) method. The mmpbsa.py47 module from AmberTools 2048 program and gmx MMPBSA v1.4.149 were used for these assays. The equations related to calculations of binding free energies (ΔGbind) were the following:\n\nWhere ΔEMM is the variation between the minimized energy of the protein-ligand complexes (EgFABP1-FAs) that includes the van der Waals (ΔEvdw) and electrostatic (ΔEele); ΔGGB is the electrostatic solvation energy, ΔGSA is the difference in surface area energies for protein and ligand and −TΔS refers to the contribution of entropy to temperature (T).\n\nSpearman’s Rho (also called Spearman’s rank correlation coefficient) was used to estimate the correlation between protein stability and binding free energy of the systems (EgFABP1-FAs). The coefficient was calculated using Python SciPy package.50 Spearman’s Rho is a rank-based non-parametric correlation measurement between two datasets, represented by a monotonic function. The Spearman’s Rho between feature X and Y is described by equation 7:\n\nWhere ρ denotes the Spearman’s Rho and n is the sample size.\n\n\nResults and discussion\n\nAccording to several studies, E. granulosus comprises a variety of strains with a comparatively high level of genetic variation. Also, numerous aspects of the parasite, such as its life cycle and transmission, pathogenicity, metabolic characteristics, and drug susceptibility, are impacted by this wide range of variety.51 Thirteen proteins with similarity to EgFABP1 were discovered by running a BLASTp search followed by phylogenetic analysis of the amino acid sequences against the E. granulosus proteome (Figure 1A). Also, understanding how successfully the proteins interfere with the complex regulatory machinery is essential, as developments in network biology have demonstrated that single-protein targeting is ineffective in treating complex disorders52; the analysis of the extended protein network showed that the proteins with the highest centrality scores on the network are annotated as mediators of RNA polymerase II transcription (Figure 1B). Additionally, the analysis of the functional enrichment for Gene Ontology (GO) revealed that the terms linked to BP were retinol metabolic process (GO:0042572) and positive regulation of biological process (GO:0048518), while retinol and fatty acid-binding proteins have been associated to suppress host immunity during nematode infection.53 Also, the GO terms associated with CC found in the analysis were intracellular organelle (GO:0043229) and organelle (GO:0043226), while the MF term was lipid binding (GO:0008289). EgFABP1 isoforms were found in the cytosolic, nuclear, mitochondrial, and microsomal fractions of the experiments, indicating that these molecules may be engaged in a variety of cellular activities54 (Figure 1C).\n\nA. Phylogenetic analysis of the amino acid sequences against the E. granulosus proteome. B. Analysis of the extended protein network of E. granulosus. C. Analysis of the functional enrichment for Gene Ontology (GO).\n\nGlobal reactivity descriptors\n\nDFT has been very successful in the last decade in predicting the chemical reactivity of various molecules.55–58 Within the DFT theory, one of the most used to determine the stability and reactivity of a particular molecule are the frontier molecular orbitals HOMO and LUMO.59,60 In Table 3, the energy values of the HOMO and LUMO orbitals for all the studied molecules match those reported in the literature for organic molecules.61 It is necessary to highlight that SFAs molecules (MTR, PDN, PLM and STA) showed the most negative values of the HOMO orbital, meaning that these molecules are the most likely to donate electrons in a chemical reaction.60,61 According to the frontier orbital theory, the energy difference between the HOMO and LUMO orbitals (HOMO-LUMO gap) is a measure of the chemical stability of a molecule in a reaction.61,62 High differences between the HOMO concerning the LUMO orbital indicate high stability of the molecule in a chemical reaction.63 Analyzing the HOMO-LUMO gap energy behaviour shown in Table 3, the SFAs molecules obtained the greatest difference in this parameter compared to the other molecules, this means that SFAs compounds present greater chemical stability according to the frontier molecular orbitals theory and the global reactivity descriptors followed by the Koopmans theory,27,56 which means that the HOMO and LUMO frontier orbitals were considered in the calculation.\n\n* μ→ correspond to Dipole Moment (debye).\n\nRegarding the dipole moment, we observed that the value decreases depending on the unsaturation degree of the FAs due to their liposolubility.64\n\nTo delve into the biological behaviour of the FAs under study, it is necessary to analyze the local reactivity descriptors such as the molecular electrostatic potential and the Fukui function. The molecular electrostatic potential provides information on the atoms of the chemical structure of a molecule with positive or negative charge density; and the Fukui function is a chemical observable that gives us the measure of which part of the molecule is more susceptible to a nucleophilic, electrophilic, or radical attack.\n\nLocal reactivity descriptors\n\nAs can be seen in Figure 2 ARA, DHA, and EPA molecules (PUFAs with the longest chains) had the most pronounced charge densities of all the compounds studied due to the structure of minimum energy in geometry optimization. These molecules have a greater torsion degree than the others, this implies that their unsaturations in addition to the carboxyl group, are very close. This generates a distribution of negative charges greater than the others. In general, the negative charge density (red lines) for all molecules were lower than the positive charge density (yellow lines), this is due to the FAs structure. These FAs molecules have between 14 and 22 carbon atoms, where the hydrocarbon chain predominates with a negative charge density towards the backbone. Likewise, the negative charge density is only located in the carboxyl group and in the unsaturations.\n\nThe negative charge density in each atom is represented in red lines and the areas with positive charge density in each molecule are represented in yellow color.\n\nThe Fukui function is a local selectivity descriptor.65–67 This parameter reveals the most susceptible molecule area of nucleophilic (f+), electrophilic (f−), and radicalary (f0) attacks.65 The Figure 3 shows that DHA, PDN, STA, and TVA molecules were the FAs with areas most susceptible to nucleophilic and electrophilic attack. These compounds have a significant concentration of positive and negative charges; the negative charge density is oriented around the unsaturations (with respect to DHA and TVA) and the carboxyl group.\n\nThe negative isovalues in each atom are represented in purple lines and the areas with positive isovalues in each molecule are represented in light blue color.\n\nThe radicalary attack behavior was different from the f+ and f−. In this case, the density obtained for all molecules was low. The f0 are focused fundamentally on the unsaturations from FAs. This result is due to fatty acids being susceptible to radical attack by reactive oxygen species in unsaturations.68–72\n\nThe molecular weight (WM), number of hydrogen bond donors (nHBD), number of hydrogen bond acceptors (nHBA), and rotatable bonds (nRot) (see Table 4); have shown acceptable values according to the data based on the “Drug-Like Soft” rule (WM(100-600), nHBA(0-12), nHBD(0-7), and nRot(0-11)). The topological polar surface area (TPSA) values of all the compounds reported 37.30 A2, which is an optimal value according to Verber’s rule (≤140 A2). Therefore, these results show that FAs would have good absorption and permeability. Likewise, all FAs are accepted for Lipinski’s rule of five ((MW≤500; logP≤5; hydrogen bond acceptor≤10; hydrogen bond donors≤5), indicating acceptable oral absorption and bioavailability.\n\na Molecular weight in g/mol.\n\nb Hydrogen bond acceptor.\n\nc Hydrogen bond donor.\n\nd Topology Polar Surface Area.\n\ne rotatable bonds.\n\nf Partition Coefficient.\n\ng Logarithm of the aqueous solubility value.\n\nh Logarithm of the n-octanol/water distribution coefficients at pH = 7.4.\n\ni Dissociation constant.\n\nThe pharmacokinetic properties are reported in Table S1 from Supporting Information. The oral adsorption logP, distribution logD, and solubility logS descriptors were evaluated. The results showed that the logP values are above the desired range (0 to 3 log mol/L), indicating that these compounds are insoluble since they are trapped in the lipophilic bilayer. This could be confirmed by the resulting values of logD (1 to 3 log mol/L) that 197 are between 3 to 5, decreasing the solubility. Furthermore, all the compounds have a pKa = 4.8 except for 7-hexadecenoic acid with a pKa = 4.6. The fatty acids analyzed show optimal values for Caco-2 (>-5.15log cm/s); indicating that they have good permeability to intestinal cell membranes. They are also a substrate for P-glycoprotein (Pgp), where Pgp is a transporter efflux out of cells of xenobiotic molecules.\n\nIn general, the FAs have a high percentage (up to 90%) of plasma protein binding (PPB), contrary to DHA and EPA with PPB83.359% and PPB89.359%, respectively. This union is determined by the structural properties of fatty acids that influence the oral bioavailability of the compounds, where a portion of the free compound could be absorbed through the membranes. The penetration of the blood-brain barrier (BBB) is important for those components that have activity in the central nervous system (CNS), some fatty acids have a better facility to penetrate the BBB than others; the values of lipophilicity, molecular weight, and TPSA allow us to predict a good penetration of the compounds to the BBB.\n\nCytochrome P450 (CYP) isoforms were also evaluated. The results indicated that fatty acids have a substrate/inhibitory effect on the CYP2C9 isoenzyme, which is important in the oxidation of xenobiotic compounds. ARA, DHA, and EPA fatty acids showed a moderate clearance of 6.011ml/min/kg, 9.988ml/min/kg, and 8.610ml/min/kg, respectively, while the other compounds had values below ≤5 ml/min/kg, indicating low excretion. Among the results, DHA and EPA present relative toxicity due to their high lipophilicity.\n\nBest protein-ligand binding models were obtained using a genetic algorithm from the Dockthor server. Additionally, an affinity prediction scoring was obtained among the fourteen FAs. This prediction affinity is used to rank different ligands in virtual screening experiments considering the “Total Energy” of each FAs.40,41 According to the score, DHA has a better affinity to EgFABP1 compared to the other FAs (see Table S2 from Supplementary Material).\n\nRegarding Molecular Dynamics analysis, Figure 4 shows the plot of RMSD (root-mean-squared deviation), RMSF (root-mean-squared fluctuation), RG (radii of gyration), SASA (solvent-accessible surface area), and HBond (intramolecular hydrogen bonds from protein) during the simulation time of 200 ns in the isobaric-isothermal ensemble. The analysis of the RMSD plot showed us the MRT, ARA, and EPA with instability from 150 to 200 ns. Similar behaviour has the RMSF analysis, in which low and high fluctuations indicate the structural mobility of each residue in molecular dynamics. The RG plot indicates low compactness between EPA and ARA. While for the SASA study, we observed that the solvent access is similar in coupled systems and apparently, the number of HBonds is reduced in coupled systems.\n\nA. Root-mean squared deviation. B. Root-mean squared fluctuation. C. Radii of gyration. D. Solvent-Accessible Surface Area. E. Intramolecular hydrogen bonds from protein.\n\nThe Table 5 shows the average values for RMSD, RMSF, RG, SASA, and HBond for the last 20 ns (same time used to estimate binding free energy by MM/GBSA). However hydrophobic interactions and salt bridges were calculated from the last frame. One of the most outstanding systems (receptor-ligand) was EgFABP1-EPA because it presents an average value of RMSD (0.50±0.07 nm), RMSF (0.17±0.08 nm), RG (1.53±0.02 nm), SASA (91.37±2.26) higher and HBond (98.00±5.00) lower than the other systems. The PLA and VAC systems show a lower RMSD (0.14±0.01 nm) and RMSF (0.10±0.04 nm) than the other systems, indicating that the protein is more stable. Additional information about the hydrophobic interactions between EgFABP1-FA are reported in Table S3 from Supplementary Material.\n\nThe binding free energy estimation was analyzed by MM/GBSA method. Table 6 shows that DHA (-38.52±2.60 kcal/mol ΔG) and PLA (-37.07±4.55 kcal/mol ΔG) obtained the best energy followed by the VAC (-36.52±2.25 kcal/mol ΔG) and OLE (-35.58±3.64 kcal/mol ΔG). All these four ligands are UFAs (i.e DHA correspond to PUFAs and the others correspond to MUFAs). These results suggest that the EgFAPB1 has a preference for unsaturated fatty acids. In parallel, it was observed that the Van der Waals energies give the greatest energy contribution.\n\nOn the other hand, EPA obtained lower binding free energy than the other FAs. Figure 5, shows how DHA (better free energy) stabilizes the protein. However, EPA (lower free energy) destabilizes the protein. According to research by Undurti N. Das,73 this effect could be beneficial in overcoming drug resistance against parasitic infections. Likewise, we observe that EPA has fewer hydrophobic interactions than DHA.\n\nAlso, we evaluated Spearman’s Rho between RMSD and binding free energy (Δ TOTAL). In the systems with better free energy, the protein tends to be more stable than without ligand, which could be inversely related. We obtain a Spearman’s Rho = 0.73 and p-value = 0.0029. The results indicate that the relationship between RMSD and binding free energy is a significant (p-value below the usual threshold of 0.05) correlation. In addition, according to most of the research reviewed,74,75 the Spearman’s Rho obtained is classified as a strong correlation.\n\n\nConclusions\n\nIn summary, this work shows an in silico approximation of fourteen fatty acids against EgFABP1 from Echinococcus granulosus. The results of global chemical reactivity descriptors demonstrated the high chemical reactivity of fatty acids, and low toxicity analyzed by ADMET properties. Structural analysis of EgFABP1 showed that it is a protein with a wide pocket with a high affinity for hydrophobic ligands. It has been observed that during the simulation time, the receptor-ligand systems with better free energy stabilize the protein, showing that this type of ligand shows a favorable behavior in the binding site of EgFABP1. Our results showed that unsaturated fatty acids and saturated fatty acids have an affinity for the active site of EgFABP1 and the best coupling was made with docosahexaenoic acid. We also observed that that eicosapentaenoic acid may possess bioactive properties against EgFABP1. These findings suggest a compelling opportunity for further exploration into the therapeutic or functional implications of eicosapentaenoic acid. Finally, these in silico studies show us a promising action of fatty acids for the research and detection of EgFABP1 in the host.",
"appendix": "Data availability\n\nFigshare. Supplementary material, https://doi.org/10.6084/m9.figshare.24534547.v1. 76\n\nThis project contains the following underlying data:\n\n• Data 1. Global Chemical Reactivity descriptors calculated from Koopmans’ theorem.\n\n• Data 2. RMSD, RMSFM, RG, SASA and Hbond averge values, N° Hydrophobic Interactions and Salt Bridges.\n\n• Data 3. Calculated MM/GBSA binding free energy of EgFABP1-Fas (kcal/mol).\n\n• Data 4. Physicochemical Properties of Fatty Acids.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgments\n\nWe appreciate the computational support of the internal project UCSM with grant number 7309-CU-2020. Yoan H. R. Yoan is grateful to the ANID- Postdoctoral 3230141. This work is similar to that existing in a preprint: https://doi.org/10.26434/chemrxiv-2023-z157s.\n\n\nReferences\n\nvan den Hoogen J , Geisen S, Wall DH, et al.: A global database of soil nematode abundance and functional group composition. Sci. Data. 2020; 7(1): 103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOtero-Abad B, Torgerson PR: A systematic review of the epidemiology of echinococcosis in domestic and wild animals. PLoS Negl. Trop. Dis. 2013; 7(6): e2249. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEckert J, Deplazes P: Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin. Microbiol. Rev. 2004; 17(1): 107–135. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoro P, Schantz PM: Echinococcosis: a review. Int. J. Infect. Dis. 2009; 13(2): 125–133. 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}
|
[
{
"id": "286385",
"date": "19 Jun 2024",
"name": "Roberto Kopke Salinas",
"expertise": [
"Reviewer Expertise I work on protein structure and dynamics using NMR spectroscopy and other methods",
"and I am interested in FABPs."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript describes a computational study of the interaction between the Echinococcus granuloses fatty acid binding protein (EgFABP1) with fatty acids. A set of 4 saturated fatty acids (C14, C15, C16 and C18), 5 monounsaturated fatty acids (C16, C18), and 5 polyunsaturated fatty acids (arachidonic, docosahexaenoic, eicosatetraenoic, linoleic, linolenic acid) were tested. Their interaction was investigated by MD simulations, and their affinities were estimated using MM/GBSA. Initial structures for fatty acids were optimized using quantum mechanics calculations, while the EgFABP1 X-ray structure was available in the PDB in the ligand bound state. Initial complexes between EgFABP1 and fatty acids were built by docking using an automated protocol (Dockthor, LNCC). Individual 200 ns MD trajectories were calculated for each complex and analyzed. The authors observed that EgFABP1 has greatest affinity for docosahexaenoic acid (DHA) followed by the cis-vaccenic acid, palmitoleic acid (PLA), trans-vaccenic acid (TVA), and oleic-acid (OLE) in this order. They also observed that binding to eicosatetraenoic acid (EPA) destabilized EgFABP1, and speculated that this molecule could have bioactive properties against EgFABP1.\n\nI am not an expert in bioinformatics nor in the prediction of chemical reactivity and toxicity. Therefore I will not comment on these parts. Concerning docking and MD simulations, I have the following comments to the authors: 1) Please provide a rationale for the selection of the 14 fatty acids used in the study 2) Which structures were chosen for the affinity prediction? Did authors use the last MD snapshot? 3) In their introduction authors stated that \"...to promote the uptake of lipids, the ligand-binding association with EgFABP1 causes a conformational change in the protein structure\". Could authors provide more information about this conformational change? 4) How long was the equilibration phase and production phase of the MD simulation? 5) By analyzing the evolution of RMSD and Rg during the MD trajectory in Figure 4, it seems that complexes with EPA, MRT (C14), and ARA are the ones that move further away from the initial structure. Would this explain their lower affinity? Could the authors suggest an explanation or a rationale for why the same behavior was not observed with other fatty acids? Furthermore, did authors run a MD trajectory with the apo protein for comparison? 6) Regarding Figure 4, how did you calculate the RMSD and RMSF? Was it over the whole complex or over the protein part, or the interface? In addition, I feel that showing number of h-bonds and SAS does not add interesting information and could be left out. 7) In the computational biology analysis, could authors explain which sequences similar to EgFABP1 were used to build the phylogenetic tree? Minor points: 1) In the second line of the last paragraph of page 14, please correct VAC for TVA 2) Table 5 could be moved to SI\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12583",
"date": "21 Nov 2024",
"name": "Haruna Barazorda-Ccahuana",
"role": "Author Response",
"response": "Thank you for your detailed comments Regarding the comment “Please provide a rationale for the selection of the 14 fatty acids used in the study”. The selection of the 14 fatty acids was based on experimental evidence, the references are added in the Molecular geometry optimization subsection. Regarding the comment “Which structures were chosen for the affinity prediction? Did authors use the last MD snapshot?”. For the affinity prediction, we utilized the last snapshot from the molecular dynamics (MD) simulation. This final snapshot was selected as it represents the equilibrated state of the protein-ligand complex, capturing the most stable and realistic conformation of the Echinococcus granulosus fatty-acid-binding protein 1 (EgFABP1) interacting with the selected fatty acids. Regarding the comment “In their introduction authors stated that \"...to promote the uptake of lipids, the ligand binding association with EgFABP1 causes a conformational change in the protein structure\". Could authors provide more information about this conformational change?”. Yes. We have added that the conformational change of the carrier protein is based on the fact that it improves its intracellular solubility. Regarding the comment “How long was the equilibration phase and production phase of the MD simulation?”. Equilibration phase: 250 ps and Production phase: 200 ns Regarding the comment “By analyzing the evolution of RMSD and Rg during the MD trajectory in Figure 4, it seems that complexes with EPA, MRT (C14), and ARA are the ones that move further away from the initial structure …”. The low affinity is because EPA, MRT, and ARA have a low number of hydrophobic interactions. Table 5 shows the values for Hydrophobic interaction. Indeed, it was possible to compare it with the apoprotein. Regarding the comment “Figure 4, how did you calculate the RMSD and RMSF? Was it over the whole complex or over the protein ..”. The RMSD and RMSF were calculated for the protein component of the complex, focusing specifically on the main chain atoms of Echinococcus granulosus fatty acid-binding protein 1 (EgFABP1). This analysis aimed to monitor the overall stability and flexibility of the protein structure throughout the molecular dynamics (MD) simulation. By adopting this approach, we evaluated how the binding of different fatty acids affects the conformational stability of the protein. Regarding the solvent-accessible surface area (SASA), it is directly linked to solubility; generally, a larger accessible surface area for polar regions of a protein enhances its solubility in polar solvents, such as water. In our results, EgFABP1 bound to EPA exhibited the highest SASA value, indicating that the misfolded structure allows for increased solvent exposure. Additionally, the analysis of hydrogen bonds provides critical insights into the protein’s structural integrity, stability, conformational dynamics, and interactions, both internally and with the surrounding environment—key factors in understanding its biological function and behavior under varying conditions. Our results showed that EgFABP1 bound to EPA formed the fewest hydrogen bonds, correlating with the lowest interaction energy. Regarding the comment “In the computational biology analysis, could authors explain which sequences similar to EgFABP1 were used to build the phylogenetic tree?”. It was included in the subsection \"Computational Biology Analysis\" Regarding the comment “In this paragraph it is important considered that Echinococcus is platyhelminth, so this first paragraph needs to be changed to focus in platyhelminth …”. This information was added in the “Introduction” section. Regarding the comment “In the similar situation in the paragraph: has shown that a diet of f (ω)-6 and (ω)-3 PUFAs is important in immunity against nematode parasites …”. This information was added in the “Introduction” section Regarding the comment “The protein structure of Echinococcus granulosus fatty-acid-binding protein I (EgFABP1) was validated in some software please indicated. Was obtained a Ramachandran plot of this structure?”. This information was added to the \"Docking and Molecular Dynamics simulation\" section Regarding the comment “Considered necessary to further describe the importance of these proteins (FAs) for diagnosis or future treatments targeting Echinococcus, please include an additional paragraph to the discussion”. This information was added in the “Discussion” section Minor points: Regarding the comment “In the second line of the last paragraph of page 14, please correct VAC for TVA”. This has been corrected. Regarding the comment “Table 5 could be moved to SI”. This has been corrected."
}
]
},
{
"id": "286389",
"date": "29 Jun 2024",
"name": "Diana G Rios-Valencia",
"expertise": [
"Reviewer Expertise Tapeworms",
"antiparasitic analysis",
"proteomics",
"recombinant proteins."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nOverall, the work âÂÂIn silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1â seems thorough and well-structured. With a very well done bioinformatic analysis, here are some suggestions which need to incorporate before accepting the article:\n1.-In this paragraph it is important considered that Echinococcus is platyhelminth, so this first paragraph needs to be changed in order to focus in platyhelminth or tapeworms: Parasitic nematodes are responsible for significant human suffering, with an astounding 1.5 billion individuals suffering from helminth infections brought on by soil. They infect people, injure cattle, and reduce food production, which results in morbidity and mortality on a global scale. àThe cestode species of the genusàEchinococcus\n2.- In the similar situation in the paragraph: has shown that a diet of (ÃÂ��)-6 and (ÃÂ��)-3 PUFAs is important in immunity against nematode parasites. However, according to Katdare Aakash et al. there are many studies of fatty acids as therapeutic additives, but more studies are still required to confirm these as unique therapeutic agents. Because of this, there is a need for greater research to determine how effective certain FAs are at preventing parasite infections caused byàE. granulosus. again it seems that echinoccocus is a nematode, consider clarifying that this is not the case.\n3.- The protein structure ofàEchinococcus granulosusàfatty-acid-binding protein I (EgFABP1)àwas validated in some software please indicated. Was obtained a Ramachandran plot of this structure?\n4.- Considered necessary to further describe the importance of these proteins (FAs) for diagnosis or future treatments targeting Echinococcus, please include an additional paragraph to the discussion. Overall, the work âÂÂIn silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1â seems thorough and well-structured. With a very well done bioinformatic analysis, here are some suggestions which need to incorporate before accepting the article.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12584",
"date": "21 Nov 2024",
"name": "Haruna Barazorda-Ccahuana",
"role": "Author Response",
"response": "Thank you for your detailed comments. Regarding the comment “In this paragraph it is important considered that Echinococcus is platyhelminth, so this first paragraph needs to be changed to focus in platyhelminth …”. Response: This information was added in the “Introduction” section. Regarding the comment “In the similar situation in the paragraph: has shown that a diet of f (ω)-6 and (ω)-3 PUFAs is important in immunity against nematode parasites …”. Response: This information was added in the “Introduction” section Regarding the comment “The protein structure of Echinococcus granulosus fatty-acid-binding protein I (EgFABP1) was validated in some software please indicated. Was obtained a Ramachandran plot of this structure?”. Response: This information was added to the \"Docking and Molecular Dynamics simulation\" section Regarding the comment “Considered necessary to further describe the importance of these proteins (FAs) for diagnosis or future treatments targeting Echinococcus, please include an additional paragraph to the discussion”. Response: This information was added in the “Discussion” section"
}
]
},
{
"id": "281773",
"date": "20 Sep 2024",
"name": "Guangyou Yang",
"expertise": [
"Reviewer Expertise parasitic disease"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript presents a computational study exploring the interaction of various fatty acids with EgFABP1, a protein crucial for lipid metabolism in Echinococcus granulosus. While the research topic is relevant and the methodology is well-described, the current manuscript is not suitable for indexing before accomplishing the following modifications.\nSpecific Comments: 1, The manuscript lacks sufficient depth in discussing the biological implications of the computational findings. While the authors mention the potential therapeutic applications, they fail to comprehensively explore how the observed interactions might affect the parasite's survival. 2, The overemphasis on DHA as the most promising candidate lacks balance and underrepresents the potential of other fatty acids. A more comprehensive analysis and comparison of different candidates, including those with higher bioavailability or better stability, is necessary. 3, The manuscript does not sufficiently explain the mechanism by which these fatty acids might affect EgFABP1 activity and the downstream effects on the parasite's biology. 4, Figure 1, depicting the phylogenetic analysis and protein network, is quite basic and lacks proper labeling. Figures 2 and 3, showcasing electrostatic potential and Fukui function, are difficult to interpret and lack concise captions. 5, Tables are generally well-presented but could benefit from clearer organization and more concise explanations for each data point. 6, The manuscript needs a more robust discussion of the biological implications of the findings. The authors should identify a specific and impactful research question driving the study. 7, The manuscript should go beyond simply stating the potential therapeutic applications of specific fatty acids. A detailed discussion of how these interactions could influence parasite biology is necessary. 8, Some information, like the classification of fatty acids, is repeated multiple times throughout the manuscript. Streamlining the text to eliminate redundancies would improve clarity and flow. 9, I would also (strongly) recommend checking the English language, the English grammar, spelling, and typing has to be carefully polished at places.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12585",
"date": "21 Nov 2024",
"name": "Haruna Barazorda-Ccahuana",
"role": "Author Response",
"response": "Thank you for your detailed comments and annotations in the copy. 1. Regarding the comment “The manuscript lacks sufficient depth in discussing the biological implications of the computational findings...”. We have added in the “Conclusion” section a focus on what is expected from these interacting systems. 2. Regarding the comment “The overemphasis on DHA as the most promising candidate lacks balance and underrepresents the potential of …”. Our results made a comparison of many FAs models reported in the literature. DHA surprised us because it showed the best performance in the study levels (quantum methods and classical methods), which seems important to us because these can modulate immune responses, influence parasite growth, and impact general dynamics. of the host-parasite relationship, with possible benefits and disadvantages for the host. 3. Regarding the comment “The manuscript does not sufficiently explain the mechanism by which these fatty acids might affect …”. In this work, we have particularly focused on understanding how an FA binds to EgFABP1 by quantum chemistry methods and classics. 4. Regarding the comment “Figure 1, depicting the phylogenetic analysis and protein network, is quite basic and lacks proper labeling. Figures 2 and 3, showcasing electrostatic potential and Fukui function, are difficult to interpret and lack concise captions”. The phylogenetic analysis is basic because there is not much information regarding EgFABP1. In the case of Figures 2 and 3, details were described in the manuscript. 5. Regarding the comment “Tables are generally well-presented but could benefit from clearer organization and more concise explanations for each data point”. Yes, each table was analyzed and explained again. 6. Regarding the comment “The manuscript needs a more robust discussion of the biological implications of the findings. The authors should identify a specific and impactful research question driving the study”. More information was added in the “Discussions” section. 7. Regarding the comment “The manuscript should go beyond simply stating the potential therapeutic applications of specific fatty acids. A detailed discussion of how these interactions could influence parasite biology is necessary”. More information was added in the “Discussions” section. 8. Regarding the comment “Some information, like the classification of fatty acids, is repeated multiple times throughout the manuscript. Streamlining the text to eliminate redundancies would improve clarity and flow”. Yes, in some cases we have removed what was redundant. 9. Regarding the comment “I would also (strongly) recommend checking the English language, the English grammar, spelling, and typing has to be carefully polished at places”. The review has already been done."
}
]
}
] | 1
|
https://f1000research.com/articles/13-303
|
https://f1000research.com/articles/13-1394/v1
|
20 Nov 24
|
{
"type": "Case Report",
"title": "Case Report: A small bowel occlusion revealed by a strangulated transomental hernia",
"authors": [
"AHMED MENIF",
"SOUHAIB ATRI",
"WASSIM RIAHI",
"HELMI ZEBDA",
"SOUHAIB ATRI",
"WASSIM RIAHI",
"HELMI ZEBDA"
],
"abstract": "Introduction Transomental hernias are a rare type of internal hernia, accounting for less than 1% of all internal hernias. They occur when abdominal contents protrude through a defect in the omentum, leading to bowel obstruction and potential strangulation. We report the case of a young male admitted for the management of an acute bowel obstruction.\n\nCase report A 38-year-old male patient with no significant medical or surgical history presented with a proximal bowel obstruction syndrome. Upon physical examination, he exhibited mild abdominal distension, tenderness in the right iliac fossa, and tympanism. Laboratory tests indicated elevated inflammatory markers. An emergency computed tomography (CT) scan suggested the presence of a congenital band or an internal hernia. A laparoscopic procedure was performed, which identified a transomental hernia with a segment of the ileum protruding through an omental defect adjacent to the transverse colon. The herniated loop of small intestine was found to be compromised and gangrenous. Due to the severity of the condition, a midline incision was made to convert the procedure, allowing for resection of the affected segment of the small intestine while preserving 2.5 meters of viable bowel distal to the duodenojejunal junction. The remaining small intestine was exteriorized as a double-barrel ileostomy, and the transomental defect was subsequently repaired. The postoperative recovery was uneventful.\n\nConclusion Although internal hernias account for a relatively small percentage of cases, they are frequently overlooked as a cause of bowel obstruction. Diagnosis this condition is challenging, both clinically and radiologically. Facilitating prompt surgical intervention to mitigate high mortality is essential.",
"keywords": [
"Transomental hernia",
"Internal hernias",
"Small bowel occlusion",
"Great omentum"
],
"content": "Introduction\n\nInternal hernias are protrusions of the viscera through a peritoneal or mesenteric opening, with the herniated viscera remaining within the abdominal cavity.1 Transomental hernias are a rare type, accounting for less than 1% of all internal hernias.2 They occur when abdominal contents protrude through a defect in the omentum, leading to bowel obstruction and potential strangulation.1 Compared to other internal hernias, transomental hernias more frequently present with strangulation of the small bowel.3 We present the case of a strangulated omental hernia to highlight the importance of early diagnosis to reduce the high risk of mortality associated with this condition.\n\n\nCase report\n\nA 38-year-old male patient, with no medical or surgical history, consulted our emergency room for an abdominal pain evolving for 48 hours accompanied by vomiting and a cessation of materials and gas, without a fever context. Clinical assessment revealed a patient who was thin and calm with a deteriorated general condition. Upon physical examination he was apyretic, stable hemodynamically and respiratorily, with a non-scarring abdomen. Notably he has a slight abdominal bloat, a defense of the right iliac fossa, and tympanism. The hernia orifices were free and the digital rectal examination normal. He had leukocytosis and neutrophilia on blood picture at 21000 and a CRP at 144. An emergent computed tomography (CT) scan performed revealed an intestinal distension proximal to a beak-shaped transitional zone located in the right paracolic gutter with decreased enhancement of the small bowel. Suspicion of a congenital band or an internal hernia ( Figures 1 and 2).\n\nGiven the clinical and radiological discrepancy, surgical treatment was opted for. Laparoscopy revealed a transomental hernia with part of ileum herniating in the omental defect close to the transverse colon. The obstructed loop of small intestine in hernia was compromised and gangrenous ( Figures 3 and 4). A conversion by the midline incision was requisite.\n\nThe compromised small intestine was resected leaving 2.5 meters of good vitality downstream of the duodenojejunal angle. Given the perioperative findings of peritonitis contraindicating anastomosis, it was decided to exteriorize the small intestine in a double gun barrel ileostomy. The transomental defect was repaired. The postoperative course was uneventful.\n\n\nDiscussion\n\nInternal hernias are protrusions of the viscera through a peritoneal or mesenteric opening, with the herniated viscera remaining within the abdominal cavity.1 The apertures for internal hernias can be classified as normal (e.g., foramen of Winslow), paranormal (e.g., paraduodenal, ileocecal, supravesical fossa), or abnormal (e.g., transomental defect) based on the typical anatomy of the abdominal cavity.4 These hernias account for 0.6% to 5.8% of all cases of intestinal obstruction.3 Transomental hernias are a rare type, accounting for less than 1% of all internal hernias.2 The greater omentum extends inferiorly from the greater curvature of the stomach to the transverse colon and beyond, draping into the anterior, inframesocolic abdomen. Omental defects can be congenital or acquired. Bowel can herniate through one to four layers of the omentum, but most commonly penetrates all four layers.5 Yamaguchi classified transomental hernias as type A (peritoneal cavity → greater omentum → peritoneal cavity), B (peritoneal cavity → omental bursa → peritoneal cavity), or C (peritoneal cavity → omental bursa).6 Our case was a type A.\n\nThis pathology occurs at all ages. However, the literature notes a predominance between 38 and 48 years. A study of 14 cases of internal abdominal hernias reported a mean age of 71 years.7 Our patient was relatively younger. Regarding gender, several studies have noted a male predominance of this condition.1 The usual way of revealing internal hernia is intestinal obstruction including nausea, vomiting, abdominal pain, distended abdomen, and constipation. Comparing with other types of intern hernias clinical signs of transomental hernia show a severe periumbilical colics accompanied by hyperactive bowel sounds and progressive distension. The surgeon can feel a sensitive abdominal mass, which represents the Gordian knot of the herniated intestine.2 Our patient showed a small bowel occlusive syndrome and a severe colic in the right iliac fossae with a slight distended abdomen.\n\nIn 2007, in a series of 14 cases, Armstrong stated that preoperative diagnosis of internal hernias was almost impossible.1 However, nowadays, several authors show the effectiveness and reliability of the abdominal CT not only to confirm the diagnosis of intestinal obstruction, but also to specify the location and type of the internal hernia.8 It can be helpful for diagnosis, revealing findings such as dilated small bowel loops pressed against the abdominal wall without omental fat causing central displacement of the colon segments and a “beak sign” at the transition zone as observed in our case. Because the defect is not visualized, the anomalies of the mesenteric vessels may be seen such as a stretched and agglomerated mesenteric vascular pedicle or a displacement of the main mesenteric.2 However, radiographic findings are often nonspecific and definitive diagnosis is usually made intraoperatively. Hence a skilled radiologist is essential to identify the subtle signs of internal hernias, which can have a significant impact on patient outcomes.\n\nPrompt surgical intervention is critical, as transomental hernias have a high postoperative mortality rate of up to 30% due to the high incidence of strangulation.5 In most cases, a gangrenous bowel is present at the exploratory laparotomy. Treatment involves reduction of the hernia contents, resection of nonviable bowel if present, and repair of the omental defect to prevent recurrence. Mortality is highest when there is a delay in diagnosis and treatment, emphasizing the importance of maintaining a high index of suspicion for this rare cause of bowel obstruction. Our patient consulted our emergency department late, which accentuated digestive ischemia and compromised his bowel loop vitality.\n\nA first laparoscopy is an emerging technic and should be attempted nowadays. A few rare cases of laparoscopic reduction of this type of hernia are described in the literature.7 In our case, it was deemed lucid to proceed with a midline incision conversion due to the presence of intestinal necrosis, in order to preserve the patient’s prognosis and ensure a successful surgical outcome.\n\n\nConclusion\n\nAlthough internal hernias account for a relatively small percentage of cases, they are frequently overlooked as a cause of bowel obstruction. Diagnosis this condition is challenging, both clinically and radiologically. Facilitating prompt surgical intervention to mitigate high mortality is essential. Abdominal CT remains a cornerstone of radiological assessment, and it has already been established that laparoscopic approach is a safe surgical approach.\n\n\nDisclaimer\n\nNo generative AI technologies such as Large Language Models (ChatGPT, COPILOT, etc.) and text-to-image generators have been used during the writing or editing of this manuscript.\n\n\nEthics\n\nEthical approval was not required.\n\n\nConsents\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patients.\n\n\nConsent to publish\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patients.\n\n\nAuthors’ contributions\n\nAuthors and affiliations:\n\nGeneral surgery department, Regional Hospital of Beja, Beja, Tunisia\n\nAhmed Menif, Souhaib Atri, Mohamed Rached Khelili, Helmi Zebda, Wassim Riahi\n\nContributions:\n\nWR contributed to work conception, MK and HZ collected data and SA revised the manuscript and AM wrote the manuscript.\n\nCorresponding author:\n\nCorrespondence to Ahmed Menif.",
"appendix": "Data availability\n\nNo data associated with this article.\n\n\nAcknowledgements\n\nThe authors confirm that all figures included in this submission are original works.\n\n\nReferences\n\nArmstrong O, Hamel A, Grignon B, et al.: Internal hernias: anatomical basis and clinical relevance. Surg Radiol Anat SRA. 2007 Jun; 29(4): 333–337. PubMed Abstract | Publisher Full Text\n\n[PDF] Intestinal obstruction Internal Hernias: Report of Clinical Cases Hernias internas: Presentación de casos clínicos|Semantic Scholar.[cited 2024 Sep 15]. Reference Source\n\nBuainain LA, Kaundinya KB, Hammed FN: Transomental hernia – An enigmatic case report causing bowel obstruction in a virgin abdomen. Int J Surg Case Rep. 2019 Nov 27; 66: 88–90. Publisher Full Text\n\nKelahan L, Menias CO, Chow L: A review of internal hernias related to congenital peritoneal fossae and apertures. Abdom Radiol. 2021 May; 46(5): 1825–1836. PubMed Abstract | Publisher Full Text\n\nA Spontaneous Transomental Hernia: A Rare Cause of Bowel Obstruction - PMC.[cited 2024 Sep 15]. Reference Source\n\nLee SH, Lee SH: Spontaneous Transomental Hernia. Ann Coloproctol. 2016 Feb; 32(1): 38–41. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMay A, Cazeneuve N, Bourbao-Tournois C: Occlusion aiguë du grêle par hernie interne dans le hiatus de Winslow: diagnostic scanographique, traitement cœlioscopique. J Chir Viscérale. 2013 Nov 1; 150(5): 373–375. Publisher Full Text\n\nMasson E. EM-Consulte: Imagerie radiologique des hernies internes.[cited 2024 Sep 15]. Reference Source"
}
|
[
{
"id": "345630",
"date": "24 Dec 2024",
"name": "Erica Nishimura",
"expertise": [
"Reviewer Expertise esophageal cancer",
"gastric cancer",
"general surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to thank the authors for the opportunity to review this manuscript.\nAlthough it is well written, there are some concerns that need to be clarified to improve the manuscript.\nWas the blood test before surgery really showed CRP as “144” or was it “14.4”? I think it would be more helpful for the readers if there were arrows in figure 1 and 2 to identify the anomality. Are there any images of the laparoscopy when you identified the hernia? Although 2.5m of small intestine was preserved, exactly what was the length of the resected intestine? The patient was young and he was hemodynamically stable, although he showed peritonitis was it really necessary to create an ileostomy?\n6.The authors showed discuss the surgical strategy in the discussion.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
},
{
"id": "352346",
"date": "20 Jan 2025",
"name": "Kehkashan Anwar",
"expertise": [
"Reviewer Expertise General Surgery"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe case report is well structured and informative.\nThe clear description of clinical presentation and surgical management provide valuable information.\nConsider providing a bit more context in the abstract to emphasize on the urgency of early diagnosis and how specific case contributes to the broader understanding of trans omental hernia. It would be helpful to highlight the diagnostic challenges in these rare hernias .\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1394
|
https://f1000research.com/articles/13-415/v1
|
29 Apr 24
|
{
"type": "Research Article",
"title": "Understanding of plagiarism amid North-African post-graduate dental students: A cross sectional pilot study",
"authors": [
"Rim Kallala",
"Mehdi Khemiss",
"Ines Azzouzi",
"Yosra Gassara",
"Soumaya Touzi",
"Belhassen Harzallah",
"Helmi Ben Saad",
"Rim Kallala",
"Mehdi Khemiss",
"Ines Azzouzi",
"Yosra Gassara",
"Soumaya Touzi",
"Belhassen Harzallah"
],
"abstract": "Background Plagiarism remains poorly understood among post-graduate dental students (PGDSs) in North Africa. Data on the level of understanding of plagiarism (UP) in this population is lacking. This study assessed UP of Tunisian PGDSs'.\n\nMethods A cross-sectional pilot study was conducted at the Faculty of Dental Medicine of Monastir, involving 147 PGDSs registered in 2022. Students were recruited via email invitations and convenience sampling at a medical congress. A French survey with 11 questions on UP, offering three-choice answers (yes/no/maybe) was administered. Each correct answer received one point, and a total UP score below six indicated a low-level of UP.\n\nResults The mean±SD UP score of the 106 students who accepted to participate in the study was 4.7±2.2, indicating a low-level of UP. The majority of PGDSs (81.13%) demonstrated a low-level of UP. A comparison between subjective and objective assessments of UP revealed that a significant percentage of PGDSs underestimated their understanding (81.13% vs. 62.26%, respectively). The two groups of PGDSs with low (n=86) and acceptable/excellent (n=20) UP showed comparable characteristics in terms of age, sex, discipline, post-graduate-level, experience-level, graduation-status, and survey-response modality.\n\nConclusion This study highlights a lack of awareness of UP among North African PGDSs, emphasizing the need for further efforts to enhance awareness and promote better UP in this population.",
"keywords": [
"Academic misconduct",
"Attitudes",
"Awareness gap",
"Dental education",
"Plagiarism assessment"
],
"content": "Introduction\n\nPlagiarism, a form of research misconduct,1 derives from the Latin term “plagiarius”, which means “kidnapper” or “abductor”.2 This longstanding issue,3 which involves the act of stealing ideas without proper attribution or crediting the original source,2 can apply to textual content, articles, or words.4 Since 1990, the term “plagiarism” has been included as a medical subject heading (MeSH) in the PubMed database search engine, with a definition as “passing off as one’s owned the work of another without credit”.4 Plagiarism is prevalent across various fields such as arts, literature, medicine, dentistry, and engineering,5,6 and its consequences can lead to article retractions.7 Despite the widespread occurrence of plagiarism between 2000 and 2023,5 studies focusing on plagiarism remain scarce. As of December 16, 2023, a search in PubMed using the MeSH term “plagiarism” yielded only 933 papers, with 12 % (n=111) of them published in the last five years (2018-2023). Several factors contribute to researchers resorting to plagiarism, including the easy availability of data5 and the increased accessibility to information on the Internet.8 The pressure to publish can also drive individuals to engage in plagiarism.9 Memon et al.10 compared plagiarism awareness among medical and non-medical students, finding statistically significant differences between them, with medical students being more susceptible to these behaviors. The literature reports a high prevalence of plagiarism among medical students.11 The lack of education about plagiarism in educational institutions is a major factor contributing to its proliferation.12 In 2023, plagiarism is widely considered one of the most persistent matters faced by higher education establishments.1\n\nA systematic review conducted in 2020, focusing on plagiarism in the dental field, concluded that this phenomenon is inevitable but varies in terms of intent, ranging from deliberate misconduct to unintentional repetition of previous ideas.13 Teaching students to avoid plagiarism is crucial for promoting academic integrity and ensuring the production of acceptable academic work.5 Consequently, assessing the “understanding of plagiarism” (UP) among students, especially those in dental education, holds significant importance. However, studies investigating UP among dental students are limited and present discrepancies.14–20 For instance, while a Brazilian study reported that 100% of students enrolled in a dentistry course at a university acknowledged that plagiarism constitutes a crime,16 an Australian study reported that 44% of post-graduate dental students did not consider plagiarism to be a problem.15 These disparities can be attributed to methodological differences in the questionnaires used to assess UP and variations in student populations.14–20 Although there are studies evaluating UP among North African dental academics,4,7 to the best of the authors’ knowledge, no research has been conducted in this area among North African dental students.\n\nGiven that UP is recognized as the first step in preventing plagiarism and considering the aforementioned points, the primary objective of this pilot study was to evaluate the level of UP among a specific sample of North African post-graduate dental students (PGDSs).\n\n\nMethods\n\nThis study is a component of a broader research project led by a dentist affiliated with a university hospital (MK in the authors’ list). The project encompasses two distinct studies. The first focused on evaluating the UP among 96 North African university hospital doctors (UHDs, 22% were dentists).4 The findings of this study revealed a lack of awareness regarding plagiarism among North African UHDs, with 74% of UHDs demonstrating a low level of UP.4 Building upon these results, the present study aims to investigate UP among a different group of participants, such as PGDSs.\n\nThe study was conducted following the guidelines established by the STROBE statement.21This cross-sectional pilot study was conducted at the Faculty of Dental Medicine of Monastir (FDMM), Tunisia, from May 2, 2022, to October 30, 2022. The research protocol was determined to be exempt from human subjects’ research review by the FDMM Ethics Committee, and therefore, formal approval was not required. For the “paper method“(Figure 1), informed written consent was obtained from each participating student. For the “electronic method” (Figure 1), the fact that the participant responded to our email and sent us the filled questionnaire as an attached file indicates his/her consent to participate in the study. The survey was administered anonymously, ensuring confidentiality. Detailed information regarding the study objectives was provided to the students, ensuring their understanding of the research purposes.\n\nTAOM: Tunisian Association of Oral Medicine. PGDSs: Post-Graduated Dental Students.\n\nThe study population consisted of all PGDSs enrolled at the FDMM during the 2022 academic year. The FDMM is the sole institution in Tunisia that offers dental medicine education, admitting approximately 30 to 40 new PGDSs each year. For the specific year under investigation (ie; 2022), the total number of PGDSs was 147, distributed as follows: 38 in the 1st year, 33 in the 2nd year, 38 in the 3rd year, and 38 in the 4th year. These PGDSs are residents who have completed their medical studies and passed the Tunisian national exam to obtain a specialist diploma.\n\nAll 147 PGDSs were invited to participate in the survey, and a five-step recruitment process, outlined in Figure 1, was implemented. To summarize, the following three recruitment methods were utilized: i) Individual emails were sent to all 147 PGDSs; ii) Announcements were disseminated through the Facebook pages of the 14 medical dental departments of the FMDM; and iii) Convenience sampling was employed, where questionnaires were distributed to PGDSs who had attended a medical congress or were acquainted with individuals involved in the study. During steps 1 to 3, which involved the electronic recruitment method, a total of 59 PGDSs were recruited. In steps 4 and 5, which involved the paper-based recruitment method, an additional 47 PGDSs were recruited.\n\nThe sample size for this study was estimated using the following formula22: n = [(Zα/2)2 × P × (1 - P) × D]/E2; where «P» represents the proportion of the main event of interest (ie; low UP), «E» is the margin of error, «Zα/2» is the normal deviate for a two-tailed alternative hypothesis at the desired level of significance, and «D» represents the design, which is equal to 1 for simple random sampling.\n\nAccording to a study conducted in Saudi Arabia,20 it was found that 17.9% of dental students (p = 0.179) were unaware of the meaning of the term “plagiarism” among a sample of 246 participants. Assuming a confidence interval of 99.9% (Zα/2 = 3.29) and a «E» of 0.065, the calculated sample size (n) was determined to be 376 participants [376 = [(3.29)2 × 0.179 × (1 – 0.179) × 1]/0.0652]. However, since our descriptive study involves a finite population (ie; a population with a limited number of participants), a correction was applied to the sample size.22 The number of students to be included after correction is given by the formula n’ = (N x n)/(N + n), where “n'” represents the corrected sample size, “N” is the size of the finite population (which is 147 in our study), and “n” is the sample size calculated from the standard formula (n=376). Therefore, the corrected minimum sample size (n’) is equal to 106 participants [106 = (147 x 376)/(147+376)].\n\nThe study employed a questionnaire written in French (See extended data Appendix A76 for the French version and Appendix B77 for the English version), and participants were not given a time limit for completing it. The questionnaire was divided into two sections. The first section focused on gathering general characteristics of the students, including age (in years), sex (ie; male/female), department such as biomaterials, dental anatomy, general anatomy, microbiology, oral physiology, oral radiology, dental surgery, endodontics, fixed prosthodontics, maxillofacial prosthesis, orthodontics, pedodontics, periodontology, and removable prosthodontics, discipline (ie; differentiating between basic sciences and clinical sciences), post-graduate level (ie; 1st year, 2nd year, 3rd year, 4th year), experience level (ie; non-experienced for 1st and 2nd years, experienced for 3rd and 4th years), response modality (ie; electronic or paper), and dental doctor graduation (ie; yes, not yet).\n\nThe second section of the questionnaire focused on the French survey, which comprised 11 questions related to UP.23 The survey was an online quiz accessible on the Laval University website.23 Each question provided three answer choices (ie; yes, no, may be), with one point awarded for each correct answer.23 A total score was calculated for each participant, and based on this score, three levels of UP were identified:\n\ni) Excellent level (score between 9 and 11): Participants at this level demonstrated the ability to use and cite sources honestly and effectively when writing a paper.\n\nii) Acceptable level (score of 7 or 8): Participants at this level need to pay attention to certain points, and consulting literature about plagiarism may be beneficial.\n\niii) Low level (score ≤ 6): Participants at this level are required to be vigilant when writing papers about plagiarism and consulting literature books on the topic is imperative.\n\nFor statistical purposes, two objective levels of UP were considered: “excellent or acceptable” and “low”.4\n\nAn additional question regarding self-assessment of UP by the PGDSs was added at the beginning of the questionnaire4: how do you evaluate your UP? Is it “low”, “acceptable” or “excellent”? Two subjective levels of understanding of plagiarism were retained: “excellent or acceptable” and “low”.4\n\nThe distribution of variables was analyzed using the Kolmogorov-Smirnov test.24 The latter involves comparing the cumulative distribution functions of the observed data with those of a theoretical distribution, typically a standard distribution like the normal or uniform distribution.24 It assesses whether the observed data follow the specified distribution or not.24 Quantitative data were presented as mean ± standard deviation (SD) with a 95% confidence interval and range [minimum-maximum]. Categorical data were presented as relative frequencies. The two-sided Chi-2 test was used to compare the percentages of PGDSs based on subjective (self-assessment) and objective (survey) assessments of UP. All statistical procedures were performed using a statistical software (StatSoft, Inc. (2014). STATISTICA (data analysis software system), version 12. www.statsoft.com, RRID: SCR_014213). The significance level was set at 0.05.\n\n\nResults\n\nOut of the 147 PGDSs invited to participate, 106 (72.11% participation rate) completed the survey. The survey was completed by 59 students (55.1%) through electronic mails and by 47 students (41.9%) through paper-based questionnaires (Figure 1).\n\nThe characteristics of the 106 PGDSs are presented in Table 1. The majority of the sample consisted of female participants (76.42%), and most of the PGDSs belonged to the clinical sciences (87.74%).\n\nTable 2 displays the results of the assessment of UP. The mean UP score was 4.7±2.2, indicating a low level of understanding. A high percentage of PGDSs (81.13%) demonstrated a low level of UP. A comparison between subjective and objective assessments revealed that a significant proportion of PGDSs underestimated their low level of UP.\n\na Number (%).\n\nb Mean ± standard deviation (95% confidence interval) [minimum-maximum].\n\nTable 3 provides the characteristics of the PGDSs categorized based on their objective level of UP (i.e.; low vs acceptable/excellent). The two groups exhibited comparable ages and comparable percentages of PGDSs in terms of sex, discipline, post-graduate level, experience level, graduation status, and response modality.\n\n\nDiscussion\n\nThis study was conducted among a sample of North-African PGDSs, as they represent future academic doctors and are required to write scientific papers. The main concerning finding of this pilot study was that 80.4% of Tunisian PGDSs demonstrated a low level of UP. Although the study was limited to Tunisia, it sheds light on the nature and extent of this problem in the North-African and/or Maghreb region. Our results reflect the magnitude of the UP issue among PGDSs in North Africa.\n\nIn recent years, the phenomenon of plagiarism has emerged as a significant ethical problem, especially among medical students, as evidenced by various studies.4,14–20,25–32 This misconduct in research writing has become widespread worldwide, with high prevalence reported among students from different continents, including America,29 Europe,26 Asia,28,33,34 and Africa.35,36 Regarding the African continent, Rohwer et al.37 examined biomedical research journal articles and found evidence of plagiarism in 63.2% of the 495 African papers studied. Plagiarism is considered a serious violation of academic integrity and a scholarly misconduct, as emphasized by Clarke et al.5 Addressing plagiarism is essential to enhance the quality of education, and avoiding plagiarism has been incorporated as a target under Sustainable Development Goal number 4 (SDG4).5 Achieving the targets of SDG4 in higher education institutions requires addressing the issue of plagiarism.5\n\nThere is a scarcity of studies specifically assessing UP among dental students.14–20 Table 4 provides a detailed overview of seven related studies. Nevertheless, to the finest of the authors’ knowledge, this is the first Tunisian and North African study to examine the issue of UP among PGDSs.\n\na Mean [Minimum-Maximum].\n\nb [Minimum-Maximum].\n\nc %.\n\nd Mean±standard deviation.\n\n\nDiscussion of results\n\nThe mean score for UP was low at 4.7±2.2, with 80.4% of PGDSs showing a low level of UP. Of concern was the finding that a significant percentage of PGDSs underestimated their level of UP (Table 2). These alarming results closely resemble those reported in a previous study conducted among Tunisian UHDs.4 Using the same French survey,23 Khemiss et al.4 reported that UHDs had a low mean score of UP (5.4±1.9), with 74% of them demonstrating low levels. Our findings suggest that Tunisian PGDSs have not received adequate guidance regarding plagiarism, a growing issue with the widespread availability of internet resources and artificial intelligence.38 This lack of understanding may be a primary reason for the prevalence of plagiarism in North African states, such as Tunisia.4 The findings also confirm a lack of awareness about plagiarism among both academics and students in Tunisian universities.\n\nThe observed low average score of UP (4.7±2.2 out of 11 questions) was intermediate compared to studies conducted among postgraduate and undergraduate dental students (Table 4). On one hand, this score was consistent with an Iranian study involving 452 PGDSs, where the mean number of correct answers to 25 plagiarism knowledge questions was low at 6.9±3.318 (Table 4). On the other hand, the local score contradicted findings from a Saudi Arabian study involving 246 dental students, where the mean plagiarism knowledge scores, assessed through 15 questions,17,39 were high at 10.4±1.1 for males and 10.5±1.2 for females20 (Table 4).\n\nThe high percentage of PGDSs displaying a low level of UP (80.4%) was also intermediate compared to percentages reported in the literature (Table 4). On one hand, our percentage aligned with findings from some studies14,16,17,19 (Table 4). For instance, 53% and 69% of 1153 dental students from 62 American and Canadian dental schools believed they should not be responsible for monitoring the academic integrity of other students and did not consider cheating a serious problem at the university.14 In a Brazilian study involving 186 dental students, 78%, 74%, 69%, 48%, and 44% of students reported a lack of respect for image copyrights, a lack of understanding of direct quotes and paraphrasing, ignorance about the different types of plagiarism, and the belief that authors can be wrongly referenced, respectively.16 An Indian study of 248 dental master’s degree students revealed that 51%, 49%, and 49% of students did not recognize plagiarism as a punishable offense, were unaware of its adverse effects on the community’s health, and did not know that software is available for plagiarism checking, respectively.17 Similarly, an Iranian study involving 102 dental students, found that 77%, 56%, 53%, 48%, and 45% of students believed using previous method descriptions was justified, self-plagiarism was not punishable, plagiarized parts of a paper could be ignored if they had scientific value, using one’s own previously published work without citation was allowed, and copying with a colleague’s permission was not wrong, respectively.19 On the other hand, the percentage in our study differed from that in some reported studies15–17 (Table 4). For instance, among Australian undergraduate students, 56% of nine postgraduate students considered plagiarism a problem, and 90% of 103 first-year students in the Bachelor of Oral Health (BOralH) and Bachelor of Dental Science (BDSc) program reported that their school had clear guidelines for dealing with plagiarism.15 In addition, 88%, 84%, and 74% of Indian dental master’s degree students were familiar with the term “plagiarism”, recognized it as an act of academic malpractice, and were aware of the mandatory dental council of India point system for scientific publications in academics.17 Some authors also reported that 100% of Brazilian students enrolled in a dentistry course were aware that plagiarism constitutes a crime.16\n\nA significant percentage of PGDSs underestimated their low level of UP. While 62.26% of PGDSs considered their UP to be low, objective evaluation increased this percentage to 81.13% (Table 2). No previous study has evaluated this issue in dental students. Our result was similar to that reported for Tunisian UHDs, where 44.8% of them perceived their UP as low, but objective evaluation raised this percentage to 74.0%.4 Our finding was partially aligned with another study comprising doctoral candidates at the Faculty of Medicine and comparing attitudes towards scientific misconduct and self-reported behavior (eg, plagiarized publication).40 This discrepancy between subjective and objective evaluations can be explained by the Kruger-Dunning effect,41 a cognitive bias in which individuals with low ability or knowledge in a particular domain tend to overestimate their competence in that domain.42 The overestimation of knowledge observed in our study aligns with results reported in various subject areas, such as logical reasoning aptitude among university students and clinical practice among specialist physicians.41–44\n\nThe two groups of PGDSs with “low” and “acceptable/excellent” UP levels showed comparable characteristics, including age, sex, discipline, post-graduate level, experience level, graduation, and response modalities (Table 3). To the best of the authors’ knowledge, no previous specific study has aimed to identify the profile of a PGDS with a low level of UP. Our finding aligns with a 2017 study that evaluated the role of plagiarism in 761 conference abstracts written by graduate students and early- to late-career faculty from approximately 70 countries.45 The study examined patterns of plagiarism among professional academic writers and found that demographic categories such as geographical location of the current institution, geographical location of the institution where the highest degree was obtained, rank, position, citizenship information, sex, and discipline were not consistent indicators of text-matching.45 However, it appears that the post-graduate level, academic year, and students’ age influence the UP level of dental students15,18 (Table 4). First, one study15 reported that the percentages of Australian undergraduate students who considered plagiarism a problem were 56%, 63%, and 83% among post-graduate students, fifth-year students of the BDSc program, and first-year students of the BOralH and BDSc program, respectively. Second, in the same study,15 the percentages of undergraduate students who believed their school had clear guidelines for dealing with plagiarism were 90%, 56%, and 44% among first-year students of the BOralH and BDSc program, post-graduate students, and fifth-year students of the BDSc program, respectively. Third, an Indian study18 identified that UP increased as the age and academic year of dental post-graduate students progressed. In contrast to our study, some authors46 reported that first-year medical dental students exhibited the highest negative attitude towards plagiarism, followed by second-year and then third-year students.\n\nFour factors may contribute to the observed low level of UP amid Tunisian PGDSs. First, there appears to be a perception of permissiveness towards plagiarism within dental medical faculties, with institution leaders exhibiting tolerance towards plagiarists, despite Tunisia implementing initiatives to combat this issue.47 Although a decree was introduced in 2008 allowing universities to autonomously sanction plagiarists, research integrity remains under-discussed, and there is a lack of initiatives to address this concern.4 The absence of comprehensive policies may explain the low level of UP among PGDSs. Fifteen years after the decree’s publication,47 it is crucial to evaluate whether policies against plagiarism in the medical field are being effectively implemented in Tunisia. Second, a significant reason for the prevalence of plagiarism is the inadequate emphasis by institutions on addressing the problem.48 The absence of mandatory training modules on research and medical writing within medical curricula may account for the observed low level of UP.49 Writing a thesis or article or dissertation is a complex task for medical students, requiring training and practice similar to any other academic skill.25,50,51 PGDSs require support from qualified supervisors to improve the quality of their academic and scientific work.50,51 Qualified supervisors play a vital role in ensuring the integrity of manuscripts produced by their students, as responsibility for suspected plagiarism is shared between senior researchers and young scientists.52 Our results are expected since some previous Tunisian studies including UHDs from different specialties including dentistry, reported a low level of awareness regarding plagiarism.4,7 These results reinforce the notion that academics who themselves lack knowledge or understanding in a particular subject (eg; UP) are less likely to effectively teach or transmit that knowledge to their students. The adage “One who lacks something cannot give it” aptly applies. Third, the low level of UP may be attributed to the lack of plagiarism detection software tools in medical faculties.53 The implementation of plagiarism detection tools has the potential to reduce the prevalence of plagiarism within institutions.4,54,55 However, it is important to consider different perspectives on the effectiveness of these tools. While Stappenbelt and Rowles.56 found that allowing students to check their own work can be beneficial and improve their skills, Youmans57 reported that the availability of such software for students does not necessarily reduce plagiarism in their own work. Additionally, Rodafinos58 concluded that expecting students to self-check their work may inadvertently encourage them to “cheat” by avoiding matches with the original sources. Since 2022, the FDMM has implemented plagiarism checker software (Turnitin), providing all teachers with access to this tool. This initiative aims to effectively raise awareness about plagiarism among students, encouraging them to use the software to check their theses and articles prior to submission. The faculty authorities are committed to promoting awareness of plagiarism and provide training to prevent its occurrence. Ford and Hughes15 found that dental students and staff expressed support for the use of Turnitin across all courses. However, a significant proportion (44%) of PGDSs expressed uncertainty regarding their stance on the use of Turnitin.15 However, it is important to note that existing plagiarism detection software tools are often limited to specific languages and can only identify copied words, while figures and other content may not be adequately compared.4,52,59,60\n\n\nDiscussion of the methodology and study limitations\n\nThe sample size calculation for this study (n=106) appears to be acceptable. It was slightly higher than the sample size of a previous Indian study, which included 102 dental students.19 However, it was significantly lower compared to the sample sizes of other relevant studies, such as 154 Australian undergraduate students,15 186 Brazilian students enrolled in a dentistry course at a university,16 246 Saudi Arabian dental students,20 248 Indian dental Master’s degree students17; 452 Indian dental post-graduate students,18 and 1153 American/Canadian dental students.14 Among these seven studies, only one20 reported the sample size calculation. Calculating the sample size is crucial as it ensures the study has a sufficient number of participants to generate statistically significant results, increases the study's power to detect meaningful effects, enhances the reliability of findings, and improves the generalizability of the results to the target population.22\n\nFollowing a similar approach to a previous North African study involving university hospital doctors,4 we combined the PGDSs with acceptable and excellent UP levels. We made this decision for two reasons. First, the number of students with an excellent UP level was low (n=8). Second, including three separate groups in a single study raises concerns about the comparability of sex distribution and postgraduate levels among the groups.4\n\nWhile various tools have been established and recommended to assess plagiarism, particularly in terms of attitudes, acceptance, and practice,17,23,28,29,39,61–64 evaluating UP is also important, especially among PGDSs. Assessing UP helps promote academic integrity, ensures ethical research practices, cultivates critical thinking skills, and enhances the quality and originality of scholarly work. This study appears to be the first to apply a virtual quiz to assess UP in students.23 We chose to use the University of Laval quiz23 to evaluate UP among Tunisian PGDSs for several reasons. First, the quiz had previously been used in a local study involving university hospital doctors.4 Second, all available surveys used to assess understanding, attitudes, practices, and knowledge related to plagiarism were in English and lacked a certified French version.17,28,29,39,61–64 Since French is the second language in Tunisia, the French Laval quiz appeared to be more suitable for Tunisian PGDSs without the need for translation or validation. Third, the Laval quiz23 is not time-consuming, requiring thoughtful responses, with an average of 15 minutes needed to answer the 11 questions.\n\nQuestionnaires have proven to be advantageous and consistent tools for evaluating attitudes, practices, and knowledge related to plagiarism.17,39,61,63,65 Some previous studies that aimed to assess UP among students in the medical or engineering fields chose to use quizzes.66–68 In other related studies (Table 4), non-standardized questionnaires were predominantly used,14–19 with the exception of one study from Saudi Arabia.20 Moreover, only two studies16,20 provided references for the questionnaires used.17,38,60\n\nSimilar to a previous Indian study,18 our study exclusively focused on PGDSs. However, in other related studies (Table 4), authors included dental students without providing further specifics,14,16,17,19,20 or both undergraduate and postgraduate students.15 We decided to concentrate on PGDSs in our study due to their requirement to complete a medical thesis as part of their graduation process. This decision was made with the intention of creating a more homogeneous sample, as PGDSs undergo a distinct academic milestone that has the potential to impact their attitudes and behaviors within our research context. This study has some limitations that need to be addressed. Firstly, as with any questionnaire-based study, the utilization of a questionnaire23 introduces subjectivity into the responses, and there is a possibility that some questions may have been answered randomly.4This introduces the potential for measurement bias, which should be considered when interpreting the results. Secondly, the use of a French quiz,23 derived from a Western academic culture within a sample representing an Eastern culture should be acknowledged. Despite the Tunisian PGDSs’ fluency in the French language, their understanding of quizzes derived from Western academic culture may differ.69 This aspect needs to be considered when interpreting the results. Additionally, the undergraduate experience and educational practices of Tunisian PGDSs occur within a culturally distinct context compared to the Canadian university system. While integrity is universally valued, its manifestations and practices may vary across different countries and cultures.69 This variation could partially explain the low level of UP among Tunisian PGDSs. Research has shown that educational practices related to honesty and quality in teaching and learning differ across cultures.69,70 For example, textual reproduction of learned content may be considered dishonorable and substandard in one culture, while it may be deemed acceptable and even necessary in another.69 Thirdly, the convenience sampling used in this study may introduce result bias as it is not representative of the entire target population, potentially leading to skewed or inaccurate findings.71 Initially, an electronic data collection method was chosen, but due to a stagnant response rate (Figure 1), the recruitment approach was modified to incorporate convenience sampling, similar to a relevant study conducted in Saudi Arabia.20 Consequently, it is important to note that our findings solely pertain to the included PGDSs.72 Caution must be exercised when interpreting the results as this sample may not be representative of all PGDSs in North Africa. A fourth limitation of our study is the absence of data regarding the number of publications and/or communications in medical congresses among the PGDSs.4 Including this information would have provided a more comprehensive understanding of the students’ profile and allowed for a more nuanced analysis by categorizing them based on their publication and communication activity. Future studies should consider collecting such data to enhance the interpretation of findings and provide a more detailed characterization of the participants.4 Finally, it would have been beneficial to include an additional validated questionnaire, such as the “Attitude toward Plagiarism” questionnaire,63 as utilized in a previous study.20 This would have enhanced the scientific rigor of our research by providing a more comprehensive assessment of students’ attitudes towards plagiarism. By incorporating established measurement tools, we could have gained valuable insights and comparisons that would contribute to the validity and generalizability of our findings.\n\nMisunderstanding plagiarism is a common occurrence, and the lack of clarity surrounding the concept makes UP essential to prevent this misconduct. However, it should be noted that UP alone is not sufficient. As highlighted by Iloh et al.,35 despite the awareness of plagiarism among Nigerian students, instances of violations were still detected. Therefore, it is crucial to focus on enhancing researchers’ knowledge and attitudes towards plagiarism, particularly among junior researchers. According to Poorolajal et al.,65 there is a significant association between the prevalence of plagiarism and an increase in scores of knowledge and attitude towards plagiarism, with a decrease of 13% and 16% per one-unit increase, respectively. This highlights the importance of researchers’ awareness regarding plagiarism. Therefore, it is crucial for scholastic programs to focus on enhancing knowledge and improving the attitude of researchers, particularly junior ones, towards plagiarism. Achieving the following three goals, as proposed by Muthanna,73 should be the target: i) Develop skills in creative, critical, and scientific thinking; ii) Encourage creative writing, translation, and publication across various disciplines; and iii) Advance knowledge through scientific research in all fields. To address these concerns, it is recommended to organize workshops, seminars, and scientific writing courses specifically focused on plagiarism.25,73 Interactive seminars have shown effectiveness in addressing this issue, as suggested by Marshal et al.74 Dedicated modules on medical research ethics and writing should be integrated into undergraduate medical curricula in North Africa to proactively prevent plagiarism.4 Combatting plagiarism is a shared responsibility, and each medical school should establish its own institutional policies to effectively address this growing phenomenon.73 Table 5 presents ten recommendations aimed at preventing plagiarism among dental medical students. By implementing these recommendations, dental medical schools can promote a culture of academic integrity and equip students with the necessary skills and knowledge to avoid plagiarism.\n\n\nConclusion\n\nThe level of UP among Tunisian PGDSs is alarmingly low, necessitating urgent action to improve it. Our study serves as an urgent call to raise awareness among North-African officials in dental faculties regarding the prevalence of plagiarism in the medical dental field. It is imperative that institutions make dedicated efforts to investigate instances of plagiarism, as dental medical faculties possess the capacity to identify fraudulent manuscripts and subsequently implement appropriate disciplinary measures against plagiarists.\n\n\nEthical approval\n\nThe research protocol was determined to be exempt from human subjects’ research review by the Ethics Committee of the Faculty of Dental Medicine of Monastir, and therefore, formal approval was not required. Our study adhered to the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/).\n\n\nInformed consent\n\nFor the “paper method”(Figure 1), informed written consent was obtained from each participating student. For the “electronic method” (Figure 1), the fact that the participant responded to our email and sent us the filled questionnaire as an attached file indicates his/her consent to participate in the study.",
"appendix": "Data availability\n\nZenodo: Excel data of the 106 Tunisian post-graduate dental students [Data set]. DOI: https://zenodo.org/records/10642001. 75\n\nThe project contains the following underlying data:\n\n- Data plagiarism.xlsx [Excel data of the 106 Tunisian post-graduate dental students]. 75\n\nZenodo: Questionnaire (version française): état de connaissance en matière de plagiat: enquête auprès des résidents en médecine dentaire. DOI: https://zenodo.org/records/10992113. 76\n\nThe project contains the following extended data:\n\n[Appendix A: Copy of the French questionnaire] (Applied questionnaire). 76\n\n- Zenodo: Questionnaire (English version). Knowledge attitudes regarding plagiarism: survey of dental medicine residents. DOI: https://zenodo.org/records/10992137. 77\n\nThe project contains the following extended data:\n\n[Appendix B: Copy of the translated English questionnaire]. 77\n\nZenodo: STROBE checklist for “Understanding of plagiarism amid North-African post-graduate dental students: A cross sectional pilot study”. Doi: https://zenodo.org/records/10692067. 78\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nIn order to correct and improve the academic writing of our paper, we have used the language model ChatGPT 3.5. 79 Authors wish also to express their sincere gratitude to all participants for their cooperation.\n\n\nReferences\n\nRodrigues F, Gupta P, Khan AP, et al.: The cultural context of plagiarism and research misconduct in the Asian region. J. Korean Med. Sci. 2023 Mar 27; 38(12): e88. Epub 20230327. eng. 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Arch Med Health Sc. 2018; 6(2): 270. Publisher Full Text\n\nMohamed ME, Mohy N, Salah S: Perceptions of undergraduate pharmacy students on plagiarism in three major public universities in Egypt. Account. Res. 2018; 25(2): 109–24. Epub 20180221. eng. PubMed Abstract | Publisher Full Text\n\nRohwer A, Wager E, Young T, et al.: Plagiarism in research: a survey of African medical journals. BMJ Open. 2018 Nov 8; 8(11): e024777. Epub 20181108. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDergaa I, Chamari K, Zmijewski P, et al.: From human writing to artificial intelligence generated text: examining the prospects and potential threats of ChatGPT in academic writing. Biol. Sport. 2023 Apr; 40(2): 615–22. Epub 20230315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGomez M, Nagesh L, Sujatha B: Assessment of the attitude towards Plagiarism among dental postgraduate students and faculty members in Bapuji Dental College and Hospital, Davangere – A cross sectional survey. IOSR-JDMS. 2014; 13(5): 01–06. Publisher Full Text\n\nHolm S, Hofmann B: Associations between attitudes towards scientific misconduct and self-reported behavior. Account. Res. 2018; 25(5): 290–300. Epub 20180625. eng. PubMed Abstract | Publisher Full Text\n\nKruger J, Dunning D: Unskilled and unaware of it: how difficulties in recognizing one's own incompetence lead to inflated self-assessments. J. Pers. Soc. Psychol. 1999 Dec; 77(6): 1121–34. Epub 2000/01/08 eng. PubMed Abstract | Publisher Full Text\n\nMahmood K: Do people overestimate their information literacy skills? A systematic review of empirical evidence on the Dunning-Kruger effect. Comminfolit. 2016; 10(2): 199–213. Publisher Full Text\n\nAbdullah JM: The eight stages of trust and “Amanah” in medicine and the Dunning-Kruger effect. Malays. J. Med. Sci. 2014 Jul; 21(4): 1–3. Epub 2015/05/16. eng. PubMed Abstract | Free Full Text\n\nLai NM, Teng CL: Self-perceived competence correlates poorly with objectively measured competence in evidence based medicine among medical students. BMC Med. Educ. 2011 May 28; 11: 25. Epub 20110528. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHodges A, Bickham T, Schmidt E, et al.: Challenging the profiles of a plagiarist: a study of abstracts submitted to an international interdisciplinary conference. Int. J. Educ. Integr. 2017 Aug 28; 13(1): 7. PMID: WOS:000410143400001. English. Publisher Full Text\n\nAlzahrani MS, Ingle NA, Assery MK: Knowledge, attitude, and practice about plagiarism among dental interns and postgraduate dental students in Riyadh city, Kingdom of Saudi Arabia. Int. J. Commun. Med. Public Health. 2020 08/28; 7(9): 3327–3334. 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Routledge; 2011 2011/11/01; 749–761.\n\nRodafinos A: Plagiarism management: Challenges, procedure, and workflow automation. Interdiscip J E-Skills Lifelong Learn. 2018 11/25; 14: 159–175. Publisher Full Text\n\nWager E: Defining and responding to plagiarism. Wiley-Blackwell; 2014; vol. 2014/01/01. : 33–42.\n\nWiedermann CJ: Ethical publishing in intensive care medicine: A narrative review. World. J Crit Care Med. 2016 Aug 4; 5(3): 171–9. Epub 20160804. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarbastefano R, Souza C: Plágio em trabalhos acadêmicos: uma pesquisa com alunos de graduação. Anais do 27° Encontro Nacional de Engenharia de Produção: 8-11 out 2007; Foz do Iguaçu, Brasil. Foz do Iguaçu: Enegep.2007; p. 1–8. (Last visit: April 18, 2024). Reference Source\n\nGhajarzadeh M, Hassanpour K, Fereshtehnejad SM, et al.: Attitude towards plagiarism among Iranian medical students. J. Med. Ethics. 2013 Apr; 39(4): 249. Epub 20120413. eng. PubMed Abstract | Publisher Full Text\n\nMavrinac M, Brumini G, Bilic-Zulle L, et al.: Construction and validation of attitudes toward plagiarism questionnaire. Croat. Med. J. 2010 Jun; 51(3): 195–201. Epub 2010/06/22. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRyan G, Bonanno H, Krass I, et al.: Undergraduate and postgraduate pharmacy students' perceptions of plagiarism and academic honesty. Am. J. Pharm. Educ. 2009 Oct 1; 73(6): 105. Epub 2009/11/04. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoorolajal J, Cheraghi P, Irani AD, et al.: Construction of knowledge, attitude and practice questionnaire for assessing plagiarism. Iran. J. Public Health. 2012; 41(11): 54–8. Epub 20121101. eng. PubMed Abstract | Free Full Text\n\nFisher ER, Partin KM: The challenges for scientists in avoiding plagiarism. Account. Res. 2014; 21(6): 353–65. Epub 2014/05/03. eng. PubMed Abstract | Publisher Full Text\n\nVarghese J, Jacob M: Do medical students require education on issues related to plagiarism? Indian. J. Med. Ethics. 2015 Apr-Jun; 12(2): 82–7. Epub 20141125. eng. PubMed Abstract | Publisher Full Text\n\nHenslee AM, Murray SL, Olbricht GR, et al.: Assessing freshman engineering students' understanding of ethical behavior. Sci. Eng. Ethics. 2017 Feb; 23(1): 287–304. Epub 20160116. eng. PubMed Abstract | Publisher Full Text\n\nHanda N, Power C: Land and discover! A case study investigating the cultural context of plagiarism. J Pract Teach Learn. 2005; 2(3): 74–95. PMID: WOS:000213530300008. English. Publisher Full Text\n\nMcInnis C: Researching the first year experience: Where to from here?. Routledge; 2010 2001/07/01; vol. 20. : 105–114. Publisher Full Text\n\nGanguli M, Lytle ME, Reynolds MD, et al.: Random versus volunteer selection for a community-based study. J. Gerontol. A Biol. Sci. Med. Sci. 1998 Jan; 53(1): M39–M46. PubMed Abstract | Publisher Full Text\n\nLucas SR: An inconvenient dataset: bias and inappropriate inference with the multilevel model. Qual. Quant. 2014; 48(3): 1619–1649. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuthanna A: Plagiarism: A shared responsibility of all, current situation, and future actions in Yemen. Account. Res. 2016; 23(5): 280–7. Epub 2016/02/19. eng. PubMed Abstract | Publisher Full Text\n\nMarshall T, Taylor B, Hothersall E, et al.: Plagiarism: a case study of quality improvement in a taught postgraduate programme. Med. Teach. 2011; 33(7): e375–81. Epub 2011/06/24. eng. PubMed Abstract | Publisher Full Text\n\nBen Saad H: Excel data of the 106 Tunisian post-graduate dental students. Zenodo. 2024. (Last visit: April 18, 2024). Reference Source\n\nBen Saad H: Questionnaire (version française): Etat de connaissance en matière de plagiat: enquête auprès des résidents en médecine dentaire. Zenodo. 2024. (Last visit: April 18, 2024). Reference Source\n\nBen Saad H: Questionnaire (English version). Knowledge attitudes regarding plagiarism: survey of dental medicine residents. Zenodo. 2024. (Last visit: April 18, 2024). Reference Source\n\nBen Saad H: STROBE checklist for “Understanding of plagiarism amid North-African post-graduate dental students: A cross sectional pilot study”. Zenodo. 2024. (Last visit: April 18, 2024). Reference Source\n\nDergaa I, Ben SH: Artificial intelligence and promoting open access in academic publishing. Tunis. Med. 2023 Jun 5; 101(6): 533–6. Epub 20230605. PubMed Abstract"
}
|
[
{
"id": "289631",
"date": "26 Jun 2024",
"name": "Vanja Pupovac",
"expertise": [
"Reviewer Expertise research integrity",
"plagiarism",
"methodology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIs the work clearly and accurately presented and does it cite the current literature? The paper could benefit from some structural modifications: Page 7, the beginning of the Discussion, should be moved to the Introduction as they are general information more appropriate at the beginning of the article. On page 13, Discussion of the methodology and study limitations, paragraph 3 – why you chose this questionnaire should be moved under Methods. Data presented in Table 4 should be integrated as a text either in the Introduction or Discussion. The literature used is comprehensive and up-to-date. Please, when you refer to your previous studies explain that one of the team members is the author of the study and that the same instrument was used (page 12, paragraphs 2 and 3).\nIs the study design appropriate and does the work have academic merit? The study design is appropriate for measuring knowledge about different forms of misconduct in the academic community. Therefore, we suggest modification in the title of the paper. Please, instead of plagiarism use misconduct in the academic community. Also, please explain why you refer to your study as a pilot study. Additionally, on page 3, paragraph 4, you mentioned that the study was a part of the broader research project, so it would be advised to provide the title and funding organization of the project. Considering the lack of studies about knowledge of plagiarism among Tunisian students, the results of this study are a valuable addition to the discussion about plagiarism. Even more, we believe that results have practical value as evidence for formulating educational programs on misconduct.\nAre sufficient details of methods and analysis provided to allow replication by others? We believe that this study could be replicated if the following modifications are conducted. Modifications regarding the instrument: Because questions in the instrument do not only describe scenarios of plagiarism but also some topics from publication ethics (Q5, Q7), and cheating in classrooms (Q9, Q10, and Q11) we suggest the authors provide a more detailed description (presumably, in Method section) of all forms of misconduct presented in the questionnaire such as verbatim plagiarism Q1, paraphrasing Q4, etc... Furthermore, it would be more appropriate to say that you measured knowledge of misconduct instead of understanding of plagiarism. Additionally, please add results for each question/scenario separately as it will show which forms of misconduct are the most and least understood. Presenting results in this way will substantially contribute to the clarity and distinctiveness of this article.\nModifications regarding the sample: Figure 1., the study flowchart, is well organized and very informative, however the procedure regarding Step 5 – recruitment of the friends of the participants remains unclear:\nIt is unclear who those friends are – are they also from your target population of PGDS at the FDMM? If yes, it would be clearer for the readers if they were called “colleagues” and not friends. Also, who administered the test to them – the researchers or their friends and if so, how did they give their survey to the researchers? How did you control that someone didn’t take the survey twice or that only the other students from FDMM took the survey?\nAdditionally, on page 4, under Study Design, paragraph 2 it should state “…PGDS who had attended TAOM congress” and not “a congress” since it was a specific congress. Page 7, Discussion, paragraph 1 – The first sentence should state: “The study was conducted on a convenient sample of PGDS from FDMM…”, and not “a sample of North-African PGDS” as it is not precise. Sample size calculation: Even though, you state the general purpose of the sample size calculation (pg. 13, paragraph 2) it is unclear why you used it because the study population is smaller than the recommended sample size calculation.\nIf applicable, is the statistical analysis and its interpretation appropriate? Comments regarding the presentation of results: Due to ethical concerns (your participants could be easily identified) we would suggest removing the distribution of participants according to the Department and Post-graduate level from Table 2. Also, please explain what Experience level means. Moreover, please check the correct percentages for low levels of UP, in Table 2 you say it’s 81,13%, but then on page 7 paragraphs 1 and 4, you write 80,4% of students had low UP. Understandably, you decided to group excellent and acceptable levels in the statistical analysis, however, in Table 2 where you show descriptive statistics, it would be better to separate those categories to show frequencies for each category (excellent, acceptable, and low) for the objective and self-assessment of UP even if you are going to merge them in the analysis. We would also advise you to please include frequencies of answers for each of the scenarios in the questionnaire and perform further analysis, for example, differences in responses regarding participants’ gender, experience, response modality, and disciplines for each question or summarize results for questions with similar scenarios (e.g., Q2 and Q5 – respect for editorial rules).\nComments regarding the interpretation of results: Please discuss the main result of your study - the lack of statistically significant difference in the level of knowledge of misconduct regarding all socio-demographic characteristics of participants (see Table 3.) Furthermore, it is not appropriate to state that you have identified the profile of the low UP students (the subchapter What is the profile of a Tunisian PGDS with a low level of UP?) when no differences were found. Your study measured only knowledge of misconduct. However, in the discussion, you often compared your results with the perception of the severity of misconduct perceived responsibility for monitoring academic integrity, or knowledge of university guidelines for dealing with plagiarism, (page 11, paragraph 3, continues on page 12).\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes, both the survey data and the questionnaire (in French and translated English versions) are available. However, we must emphasize our major concern regarding data presented in the supplement material of the article – Data set (Zenodo: Excel data of the 106 Tunisian post-graduate dental students [Data set]. DOI: https://zenodo.org/records/10642001.75) More precisely, it is not clear why 6 students were given 6 points on Q5 in the Excel table (cells R100, R103-107) while all other answers are 0 and 1 (and you have mentioned that they were given a point for each correct answer). If you remove those 6 points they would be in another UP category.\nAre the conclusions drawn adequately supported by the results? The recommendations organized in Table 5 are overreaching the results of the study. We suggest that recommendations be more specific, for example, you could suggest learning outcomes for educational courses on misconduct.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12344",
"date": "21 Oct 2024",
"name": "Helmi BEN SAAD",
"role": "Author Response",
"response": "Comment N° 1. Is the work clearly and accurately presented and does it cite the current literature? The paper could benefit from some structural modifications: a. Page 7, the beginning of the Discussion, should be moved to the Introduction as they are general information more appropriate at the beginning of the article. b. On page 13, Discussion of the methodology and study limitations, paragraph 3 – why you chose this questionnaire should be moved under Methods. c. Data presented in Table 4 should be integrated as a text either in the Introduction or Discussion. d. The literature used is comprehensive and up-to-date. e. Please, when you refer to your previous studies explain that one of the team members is the author of the study and that the same instrument was used (page 12, paragraphs 2 and 3). RESPONSE .Thank you for all your excellent remarks. All structural modifications requested by the reviewers were applied. a. We have moved the beginning of the Discussion to the Introduction b. We have moved the paragraph 3 related to “why we chose this questionnaire” from the Discussion s to the Methods c. Data presented in Table 4 are integrated as a text in the Discussion d. Thank you for this positive feedback e. Thank you for this remark pertinent. In the paper, when we referred to our previous study, we have explained that 2 authors of the team members are the authors of the study and that the same instrument was used TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. The sentence (please, see below) was moved from the Discussion to the beginning of the Introduction, and we have applied all needed arrangements (Lines 24-35): In recent years ( i.e. ; after 2000), the phenomenon of plagiarism has emerged as a significant ethical problem, 7especially among medical students, as evidenced by various studies. 4 , 13-27 This misconduct in research writing has become widespread worldwide, with high prevalence reported among students from different continents, including America, 28 Europe, 21 Asia, 23 , 29 , 30 and Africa. 31 , 32 Regarding the African continent, Rohwer et al. 33 examined biomedical research journal articles and found evidence of plagiarism in 63.2% of the 495 African papers studied. Plagiarism is considered a serious violation of academic integrity and a scholarly misconduct, as emphasized by Clarke et al. 5 Addressing plagiarism is essential to enhance the quality of education, and avoiding plagiarism has been incorporated as a target under Sustainable Development Goal number 4 (SDG4). 5 Achieving the targets of SDG4 in higher education institutions requires addressing the issue of plagiarism. 5 b. We have moved the paragraph 3 related to “why we chose this questionnaire” from the Discussion to the Methods. We have applied all needed arrangements (Lines 161-175): Why we have chosen the Laval University quiz 23? While various tools have been established and recommended to assess plagiarism, particularly in terms of, attitudes, acceptance, and practice, 16 , 23 , 24 , 35 , 40 - 44 evaluating KoM is also important, especially among PGDSs. Assessing KoM helps promote academic integrity, ensures ethical research practices, cultivates critical thinking skills, and enhances the quality and originality of scholarly work. Our study appears to be the first to apply a virtual quiz to assess students’ KoM. 35 We opted for the Laval University quiz 35 to evaluate KoM among Tunisian PGDSs for several reasons. First, the quiz was previously used in a local study involving UHDs. 4 Second, all available surveys used to assess understanding; attitudes, practices, and knowledge related to plagiarism were in English and lacked a certified French version. 16 , 23 , 24 , 40 - 44 Since French is the second language in Tunisia, and since medical teaching is in French, the French Laval quiz appeared to be more suitable for Tunisian PGDSs without the need for translation or validation. Third, the Laval quiz 35 is not time-consuming, requiring thoughtful responses, with an average of 15 minutes needed to answer the 11 questions. c. Data presented in Table 5 (which was old Table 4) are integrated as a text in the Discussion. Please see when we often refer to Table 5. For example, the following sentence exists in the Discussion (Lines 233-236): There is a scarcity of studies specifically assessing KoM among dental students. 13 – 19 Table 5 provides a detailed overview of seven related studies. 13 – 19 Nevertheless, to the finest of the authors’ awareness, this is the first Tunisian and North-African study to examine the issue of KoM among PGDSs. d. No action is needed. e. When we referred to our previous study (reference 4), we have explained that 2 authors of the team members are the authors of the previous study, and that the same instrument was used (Lines 65-68): Two of the team members of this study (MK and HBS in the authors’ list) are the authors of the abovementioned study. 4 Moreover, the same instrument (i.e. ; an online quiz accessible on the Laval University website 35) was used in both studies. Comment N°2. Is the study design appropriate and does the work have academic merit? a. The study design is appropriate for measuring knowledge about different forms of misconduct in the academic community. Therefore, we suggest modification in the title of the paper. Please, instead of plagiarism use misconduct in the academic community. b. Also, please explain why you refer to your study as a pilot study. c. Additionally, on page 3, paragraph 4, you mentioned that the study was a part of the broader research project, so it would be advised to provide the title and funding organization of the project. d. Considering the lack of studies about knowledge of plagiarism among Tunisian students, the results of this study are a valuable addition to the discussion about plagiarism. Even more, we believe that results have practical value as evidence for formulating educational programs on misconduct. RESPONSE a. Thank you for your positive feedback. We have accepted your suggestion and instead of plagiarism we have used, overall the paper knowledge of misconduct (abbreviated as KoM) b. We have deleted the term pilot from the title and all the paper c. Our study was a part of a broader research project titled: plagiarism knowledge and understanding in Tunisian university. The project has no funding organization d. Thank you for your positive feedback TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. The new title is : Knowledge of misconduct amid North-African post-graduate dental students: A cross sectional study b. We have deleted the term pilot from the title and all the paper. c. We have added the following sentence in the text (Lines 57-68): This study is a component of a broader research project titled “plagiarism knowledge and understanding in Tunisian universities” led by two university hospital doctors (UHDs) [i.e. ; a dentist and a physiologist (MK and HBS, in the authors’ list, respectively)]. The project encompasses two distinct studies. The first focused on evaluating the plagiarism understanding among 96 North-African UHDs (22% were dentists). 4 The findings of the aforementioned study revealed a lack of awareness regarding plagiarism among North-African UHDs, with 74% of them demonstrating a low-level of plagiarism understanding. 4 Building upon these results, the present study aims to investigate KoM among a different group of participants, such as PGDSs. d. We have added the following sentence in the conclusion (Lines 526-527): Our results have practical value as evidence for formulating educational programs on plagiarism/misconduct. Comment N°3. Are sufficient details of methods and analysis provided to allow replication by others? a. We believe that this study could be replicated if the following modifications are conducted. Modifications regarding the instrument: Because questions in the instrument do not only describe scenarios of plagiarism but also some topics from publication ethics (Q5, Q7), and cheating in classrooms (Q9, Q10, and Q11) we suggest the authors provide a more detailed description (presumably, in Method section) of all forms of misconduct presented in the questionnaire such as verbatim plagiarism Q1, paraphrasing Q4, etc... b. Furthermore, it would be more appropriate to say that you measured knowledge of misconduct instead of understanding of plagiarism. c. Additionally, please add results for each question/scenario separately as it will show which forms of misconduct are the most and least understood. Presenting results in this way will substantially contribute to the clarity and distinctiveness of this article. RESPONSE a. We have accepted your suggestion. In the Methods, we have provided a more detailed description of all forms of misconduct presented in the questionnaire such as .Verbatim plagiarism: Q1 to Q3 .Paraphrasing: Q4 .Publication ethics: Q5 to Q8 .Cheating in classrooms: Q9 to Q11 b. We agree with the reviewers. Please see our response to your comment N°2a c. Thank you for this excellent suggestion. We have added a Table including results for each question (questions 1 to 11) and the four forms of misconduct. We agree with the reviewer that presenting results in this way will substantially contribute to the clarity and distinctiveness of our article TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. We have added the following sentence inside the Methods (Lines 155-160): The 11 questions explore the following four forms of misconduct: Verbatim plagiarism (questions 1 to 3), paraphrasing (question 4), publication ethics (questions 5 to 8), and cheating in classrooms (questions 9 to 11). Scores for each question ( i.e. ; 11 questions) and for the four forms of misconduct were calculated. The percentages of participants who responded correctly to each question ( i.e. ; 11 questions) and to all questions of each form of misconduct were calculated. .Moreover, see the discussion part reserved to the 4 forms of misconduct b. Please see the revised version of our paper and our response to your comment N°2a c. Please, see the new added Table: now Table 3 and related text in the Results. We have added the following sentence (Lines 207-213): Table 3 displays the results for the 11 and the four forms of misconduct ( i.e. ; verbatim plagiarism, paraphrasing, publication ethics, and cheating in classrooms). The percentages of students having correct answers to each question varied from 17.9% (question 11) to 61.3% (questions 8 and 10). The percentages of students having correct answers to questions of each form of misconduct varied from 0.0% (verbatim plagiarism and publication ethics) to 36.8% (paraphrasing). Only one student answered correctly to the three questions related to cheating in classrooms. Comment N°4. Modifications regarding the sample: Figure 1., the study flowchart, is well organized and very informative, however the procedure regarding Step 5 – recruitment of the friends of the participants remains unclear: a. It is unclear who those friends are – are they also from your target population of PGDS at the FDMM? If yes, it would be clearer for the readers if they were called “colleagues” and not friends. b. Also, who administered the test to them – the researchers or their friends and if so, how did they give their survey to the researchers? How did you control that someone didn’t take the survey twice or that only the other students from FDMM took the survey? c. Additionally, on page 4, under Study Design, paragraph 2 it should state “…PGDS who had attended TAOM congress” and not “a congress” since it was a specific congress. RESPONSE 4. Thank you for your positive feedback concerning Figure 1. Procedure regarding Step 5 is improved: please, see the new Figure 1: a. Yes, “friends” were also from our target population of PGDS at the FDMM? We have renamed them “colleagues” b. Thank you for your excellent remarks. Two researchers (RK and MK in the authors’ list) administered the test to the PGDSs. All additional information were added inside the paper c. The sentence was corrected inside Figure 1 and text TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE 4. Please, see the revised Figure 1. a. Please see the revised Figure 1 and note that we have reported: STEP 5: Paper method (October 1, 2022) Questionnaires directly delivered to a selected group of colleagues chosen from the 147 PGDSs list (n=15 who had not taken the survey before). b. We have added the following sentence (Lines 93-106): All 147 PGDSs were invited to participate in the survey, and a five-step recruitment process, outlined in Figure 1, was implemented. To summarize, the following three recruitment methods were utilized: i) Individual emails were sent to all 147 PGDSs; ii) Announcements were disseminated through the Facebook pages of the 14 medical dental departments of the FMDM; and iii) Convenience sampling was employed, where questionnaires were distributed to PGDSs who had attended the medical congress of the Tunisian Association of Oral Medicine (n=32) or were acquainted with authors involved in the study ( i.e. ; 15 colleagues chosen from the 147 PGDSs ‘list and who had not taken the survey before). During steps 1 to 3, which involved the electronic enrolment method, 59 PGDSs were recruited. In steps 4 and 5, which involved the paper-based enrolment method, an additional 47 PGDSs were recruited. During the paper-based enrolment method ( i.e. ; steps 4 and 5), two researchers (RK and MK in the authors’ list) asked the PGDSs if they had taken the survey before. If they had not, the researchers administered the questionnaire and collected the surveys from the PGDSs upon completion. c. The following sentence was added (Lines 98-99): …. who had attended the medical congress of the Tunisian Association of Oral Medicine (n=32) or were Comment N°5. Page 7, Discussion, paragraph 1 – The first sentence should state: “The study was conducted on a convenient sample of PGDS from FDMM…”, and not “a sample of North-African PGDS” as it is not precise. RESPONSE .Thank you. Correction done TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .The sentence was corrected (Lines 227-228): This study was conducted on a convenient sample of 106 PGDSs from FDMM, as they represent future academic doctors and …… Comment N°6. Sample size calculation: Even though, you state the general purpose of the sample size calculation (pg. 13, paragraph 2) it is unclear why you used it because the study population is smaller than the recommended sample size calculation. RESPONSE .Thank you for this remark .We calculated the sample size to inform the readers about the confidence interval of our study (ie; 99.9%) and mainly to know when to stop the recruitment of students .Before the beginning of the study, we have consulted an experienced statistician who helped us writing this important section .We are aware that the study population is smaller than the recommended sample size calculation. This is explained by the fact that our study involves a finite population (ie; a population with a limited number of participants), and therefore a correction was applied to the sample size. In practice, to calculate the sample size in a finite population, we use a formula that accounts for the finite population correction (FPC). This correction is necessary when the population size is small relative to the sample size because it reduces the required sample size compared to what would be needed for an infinite population. The FPC is necessary when the sample is a significant fraction of the population (usually more than 5-10% of the population). Without this correction, the sample size would be overestimated, leading to inefficiencies. Please see: Kish, L. (1965). Survey Sampling. New York: John Wiley & Sons TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .No action is needed. Comment N°7. If applicable, is the statistical analysis and its interpretation appropriate? Comments regarding the presentation of results: a. Due to ethical concerns (your participants could be easily identified) we would suggest removing the distribution of participants according to the Department and Post-graduate level from Table 2. b. Also, please explain what Experience level means. RESPONSE a. Thank you for this important ethical concern. We have removed the distribution of participants according to the Department (but not according to Post-graduate level) from Table 1. Since there are several students in each post-graduate level, it is impossible to identify them b. Experience level was arbitrarily defined as; non-experienced for 1 st and 2 nd years of study, and experienced for 3 rd and 4 th years of study TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. We have removed the distribution of participants according to the Department and from Table 1. In addition, all needed changes inside the Methods were done b. We have reported the following sentence inside the paper (Lines 133-135): experience level (arbitrarily defined as non-experienced for 1 st and 2 nd years, and experienced for 3 rd and 4 th years), Comment N°8. Moreover, please check the correct percentages for low levels of UP, in Table 2 you say it’s 81,13%, but then on page 7 paragraphs 1 and 4, you write 80,4% of students had low UP. RESPONSE .Thank you for your remark and sorry for this mistake .After taking into consideration all your excellent remarks, we have corrected all the percentages TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .In the revised version, and after taking into account all your remarks, the percentage for low KoM level is 85.85% . Comment N°9. Understandably, you decided to group excellent and acceptable levels in the statistical analysis, however, in Table 2 where you show descriptive statistics, it would be better to separate those categories to show frequencies for each category (excellent, acceptable, and low) for the objective and self-assessment of UP even if you are going to merge them in the analysis. RESPONSE .Thank you for your remark and sorry for this mistake .All needed corrections were done TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .In Table 2 you can see the frequencies for each category (excellent, acceptable, and low) for the objective and self-assessment of KoM. Please see the revised Table 2. Comment N°10. We would also advise you to please include frequencies of answers for each of the scenarios in the questionnaire and perform further analysis, for example, differences in responses regarding participants’ gender, experience, response modality, and disciplines for each question or summarize results for questions with similar scenarios (e.g., Q2 and Q5 – respect for editorial rules). RESPONSE .Thank you for these suggestions .First, we have included frequencies of answers for each of the scenarios in the questionnaire and for the 4 forms of misconducts (what you rename questions with similar scenarios): Table 3 .Second, your suggestion to perform further analysis, for example, differences in responses regarding participants’ gender, experience, response modality, and disciplines for each question is interesting. However, in order to send a clear message and keep the paper as short as possible, we decided to plane these analyses during an upcoming study. Thank you for the excellent idea TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .Please see the new Table 3. Comment N°11. Comments regarding the interpretation of results: a. Please discuss the main result of your study - the lack of statistically significant difference in the level of knowledge of misconduct regarding all socio-demographic characteristics of participants (see Table 3) b. Furthermore, it is not appropriate to state that you have identified the profile of the low UP students (the subchapter What is the profile of a Tunisian PGDS with a low level of UP?) when no differences were found. c. Your study measured only knowledge of misconduct. However, in the discussion, you often compared your results with the perception of the severity of misconduct perceived responsibility for monitoring academic integrity, or knowledge of university guidelines for dealing with plagiarism, (page 11, paragraph 3, continues on page 12). RESPONSE a. In the revised version, we have discussed the lack of statistically significant difference in the KoM level regarding all socio-demographic characteristics of participants. For that reason, we have consulted the following references: 1.Perkins M, et al. Reducing plagiarism through academic misconduct education. Int J Educ Integr. 2020 2020/05/01;16(1):3. 2.Perkins M, et al. Plagiarism in higher education: classification, causes and controls. Pan-Pacific Management Science. 2019;2:3-20 3.Holm S, Hofmann B. Investigating the Reliability and Factor Structure of Kalichman's \"Survey 2: Research Misconduct\" Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral Students in Scandinavia. J Empir Res Hum Res Ethics. 2017 Oct;12(4):199-205. 4.Jereb E, et al. Factors influencing plagiarism in higher education: A comparison of German and Slovene students. PLoS One. 2018;13(8):e0202252. 5.Patil VL, Ganganahalli P. Perception of Plagiarism Among Medical Postgraduate Students: An Observational Study. Cureus. 2024 Jul;16(7):e64513. RESPONSE b. We agree with the reviewer that it is not appropriate to state that we have identified the profile of the students with low KoM level when no differences were found. Changes were introduced in the paper. c. We agree that our study measured only KoM. However, since the pioneer character of our study, we sometimes compared our results with the perception of the severity of misconduct perceived responsibility for monitoring academic integrity, or knowledge of university guidelines for dealing with plagiarism. Needed changes were introduced in the Discussion. TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. We have added the following sentence (Lines 315-345): Which factors influence the KoM level of Tunisian PGDS? The two groups of PGDSs with “low” and “acceptable or excellent” levels of KoM showed comparable characteristics, including age, sex, discipline, post-graduate level, experience level, graduation, and response modalities (Table 4). To the best of the authors’ knowledge, while several studies have tried to identify the influencing factors of plagiarism and misconduct in higher education. 14 17 55 - 61, no previous specific study has aimed to identify the factors that influence the KoM’ level of PGDS. Our finding aligns with a 2017 study that evaluated the role of plagiarism in 761 conference abstracts written by graduate students and early- to late-career faculty from approximately 70 countries. 55 The study examined patterns of plagiarism and misconduct among professional academic writers and identified that demographic categories such as geographical location of the current institution, geographical location of the institution where the highest degree was obtained, rank, position, citizenship information, sex, and discipline were not consistent indicators of text-matching. 55 However, it appears that the post-graduate level, academic year, and students’ age influence the KoM’ level of dental students 14 , 17 (Table 5). First, one study 14 reported that the percentages of Australian undergraduate students who considered plagiarism a problem were 56%, 63%, and 83% among post-graduate students, fifth-year students of the BDSc program, and first-year students of the BOralH and BDSc program, respectively. Second, in the same study, 14 the percentages of undergraduate students who believed their school had clear guidelines for dealing with plagiarism were 90%, 56%, and 44% among first-year students of the BOralH and BDSc program, post-graduate students, and fifth-year students of the BDSc program, respectively. Third, an Indian study 17 identified that KoM increased as the age and academic year of dental post-graduate students progressed. In contrast to our study, some authors 56 reported that first-year medical dental students exhibited the highest negative attitude towards plagiarism, followed by second-year and then third-year students. Fourth, Perkins et al. 58 identified other factors that influence KoM, including English language abilities, personality traits, and student experience and education on plagiarism. Finally, in an empirical study, 62 hospitality students advanced six key factors in order to explain cases of extreme plagiarism including a poor time management, fear of failure, improve grade point average, personal/family problems, poor level of English, and unsure about referencing and plagiarism policy.” b. The subtitle “What is the profile of a Tunisian PGDS with a low level of UP?” was changed by “Which factors influence the KoM level of Tunisian PGDS?” c. The Discussion was improved taking into account your remarks and those of the second reviewers. Comment N°12. Are all the source data underlying the results available to ensure full reproducibility? a. Yes, both the survey data and the questionnaire (in French and translated English versions) are available. b. However, we must emphasize our major concern regarding data presented in the supplement material of the article – Data set (Zenodo: Excel data of the 106 Tunisian post-graduate dental students [Data set]. DOI: https://zenodo.org/records/10642001.75). More precisely, it is not clear why 6 students were given 6 points on Q5 in the Excel table (cells R100, R103-107) while all other answers are 0 and 1 (and you have mentioned that they were given a point for each correct answer). If you remove those 6 points they would be in another UP category. RESPONSE a. Thank you. b. Yes, the reviewers have right and we thank them for identifying this major concern regarding data presented in the supplement material of the article. We have corrected the mistakes and two authors reevaluated all statistics. When we have removed the 6 points, all levels were changed. TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. No action is needed b. Please see the revised results and Tables 2, 3, and 4. We have uploaded a revised version of our Data set. Please see the revised reference 75. Comment N°13. Are the conclusions drawn adequately supported by the results? a. The recommendations organized in Table 5 are overreaching the results of the study. b. We suggest that recommendations be more specific, for example, you could suggest learning outcomes for educational courses on misconduct. RESPONSE a. We agree with the reviewer that our recommendations organized in Table 6 are overreaching the results of the study. For that reason, we have deleted them. b. We agree with the reviewers’ suggestion that recommendations must be more specific, for example, we have suggested learning outcomes for educational courses on misconduct. TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. The table was deleted. b. As recommended, we have suggested learning outcomes for educational courses on misconduct. Please see the following sentences (Lines 518-521): Dedicated modules on medical research ethics and writing, and learning outcomes for educational courses on plagiarism/misconduct should be integrated into undergraduate medical curricula in North-Africa to proactively prevent plagiarism/misconduct. 4 Comment N° 14. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly RESPONSE .Thank you again for your positive and constructive remarks and suggestions. .We hope that our revised version is now acceptable."
}
]
},
{
"id": "299554",
"date": "26 Jul 2024",
"name": "Ulaş Başar Gezgin",
"expertise": [
"Reviewer Expertise cognitive science",
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],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI appreciate efforts by the researchers, but there are fundamental issues about this paper. For one thing, the definition of plagiarism should be inclusive of various academic misconduct cases. But this paper focuses on a particular form of plagiarism. Secondly, the statistics used is descriptive. That is possibly due to the design of the questionnaire. But it is known that the information to be provided by descriptive methods is limited. I would have expected the researcher to use inferential statistics. Thirdly, even the use of inferential statistics would allow limited conclusions. Thus, this research study had to be complemented by an intervention program where post and pre tests were considered. This intervention program could have been a form of training. Fourthly, we had shown in our study that plagiarism is also related to limited language ability. The questionnaire is in French. The questions, I guess, are unintentionally measuring language ability. That had to be checked by a language test score. Finally, we need to consider the fact that the participants are dentistry students. It would have been better to design the questions relevant for their subject area. In this form, the questions are too far away from the realities of plagiarism. Thus, for these reasons, I think this paper shouldn't be indexed. Thank you very much, Best regards,\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12345",
"date": "21 Oct 2024",
"name": "Helmi BEN SAAD",
"role": "Author Response",
"response": "COMMENT I appreciate efforts by the researchers, but there are fundamental issues about this paper. RESPONSE .Thank you for your effort to revise our paper. .We tried to consider all your remarks, when it is possible. .Taking into account the remarks of the first reviewers, and yours, we hope that our paper is improved and can be candidate for a publication. COMMENT For one thing, the definition of plagiarism should be inclusive of various academic misconduct cases. But this paper focuses on a particular form of plagiarism. RESPONSE .As you can see, we have changed plagiarism by knowledge of misconduct (as suggested by the first reviewers) and we have identified four forms of misconduct: (i.e.; verbatim plagiarism, paraphrasing, publication ethics, and cheating in classrooms). COMMENT a. Secondly, the statistics used is descriptive. That is possibly due to the design of the questionnaire. But it is known that the information to be provided by descriptive methods is limited. b. I would have expected the researcher to use inferential statistics. RESPONSE a. We partially agree with the reviewers’ that our statistics are only descriptive. .On the one hand, as you can see in Table 4, we have compared the characteristics of the 106 PGDSs divided according to the objective level of KoM. .On the other hand, descriptive methods are crucial for understanding the distribution and characteristics of variables within a population. Here are two main importance of the information provided by descriptive methods, particularly in the context of assessing the level of KoM among PGDSs: 1. Baseline understanding and characterization: -Importance: Descriptive methods provide a clear picture of the current state of knowledge or behavior within a population. For example, when studying KoM among PGDSs, descriptive statistics can reveal the average level of knowledge, the distribution of responses, and the frequency of various levels of awareness or misunderstanding about misconduct. -Benefit: This baseline understanding helps identify the extent of the issue and characterize the population's knowledge. It can highlight areas where students have strong knowledge or significant gaps. This information is crucial for tailoring educational interventions and improving training programs to address specific issues. 2. Identifying patterns and trends: -Importance: Descriptive methods allow for the identification of patterns and trends within the data. For instance, descriptive statistics can show if there are particular subgroups (e.g., based on year of study or previous training) that have higher or lower levels of KoM. -Benefit: Recognizing these patterns helps in understanding how KoM varies across different segments of the student population. It can guide targeted efforts to address specific groups with lower knowledge levels, ensuring that interventions are more effective and relevant. Overall, descriptive methods are foundational for summarizing and interpreting data, which informs further analysis and decision-making. .The following references argued our scientific response: Bland JM, Altman DG. Measurement error. BMJ. 1996 Jun 29;312(7047):1654. doi: 10.1136/bmj.312.7047.1654. Corrected and republished in: BMJ. 1996 Sep 21;313(7059):744. doi: 10.1136/bmj.313.7059.744. PMID: 8664723; PMCID: PMC2351401 Trochim W, Donnelly JP, Arora, K. Research Methods: The Essential Knowledge Base. 2nd Edition. 2016. Cengage Learning b. We understand the expectation of the reviewers to see inferential statistics. The primary advantage of inferential statistics over descriptive statistics lies in its ability to make generalizations and predictions about a population based on sample data. While descriptive statistics summarize and describe the features of a dataset, such as measures of central tendency and variability, inferential statistics use sample data to draw conclusions about a larger population, making it possible to test hypotheses, estimate parameters, and make predictions. While descriptive statistics provide a snapshot of the data, which is limited to summarizing the characteristics of the sample or dataset at hand, they do not offer insights beyond the data collected, nor do they account for sampling variability or uncertainty. In contrast, inferential statistics allow researchers to extend findings from a sample to the broader population from which the sample was drawn. Inferential statistics help to assess the reliability of observed patterns and make predictions or generalizations with quantifiable confidence. TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE a. Inside the paper, in the discussion of the methods we have added the following sentence (Lines 403-422): Descriptive methods are crucial for understanding the distribution and characteristics of variables within a population. 77, 78 In the context of assessing the KoM level among PGDSs, the information provided by descriptive methods are important for at least two reasons, which are determination of baseline knowledge and characterization and identifying patterns and trends. 77, 78 First, descriptive methods provide a clear picture of the current state of knowledge or behavior within a population. 78 For example, when studying KoM among PGDSs, descriptive statistics can reveal the average level of KoM, the distribution of responses, and the frequency of various levels of awareness or misunderstanding about misconduct. This baseline understanding helps identify the extent of the issue and characterize the population's knowledge. It can highlight areas where students have strong knowledge or significant gaps. This information is crucial for tailoring educational interventions and improving training programs to address specific issues. Second, descriptive methods allow for the identification of patterns and trends within the data. 78 For instance, descriptive statistics can show if there are particular subgroups (e.g. ; based on year of study or previous training) that have higher- or lower- levels of KoM. 78 Recognizing these patterns helps in understanding how KoM varies across different segments of the student population. It can guide targeted efforts to address specific groups with lower knowledge levels, ensuring that interventions are more effective and relevant. Overall, descriptive methods are foundational for summarizing and interpreting data, which informs further analysis and decision-making. b. In the study limitations subsection, we have added the following sentence (Lines 480-490) Seventhly, it was better to perform inferential statistics, in addition to the descriptive ones. The primary advantage of inferential statistics over descriptive statistics lies in its ability to make generalizations and predictions about a population based on sample data. 87 Inferential statistics allow researchers to extend findings from a sample to the broader population from which the sample was drawn, help to assess the reliability of observed patterns, and make predictions or generalizations with quantifiable confidence. 87 Eighthly, it was better to check the students’ language ability, since they often claim that English language ability is one of the main reasons why they commit plagiarism/misconduct offences. 88 Some authors reported statistically significant differences in the English language abilities of students who have previously committed plagiarism/misconduct offences, compared to students who have not. 88 COMMENT Thirdly, even the use of inferential statistics would allow limited conclusions. Thus, this research study had to be complemented by an intervention program where post and pre tests were considered. This intervention program could have been a form of training. RESPONSE .We understand the point of view of the reviewers .Your remarks are added in the manuscript in the section named “study limitation” .As now, we have a general idea about the phenomenon of low KM among PGDSs, we are planning to perform an interventional study where post- and pre- tests will be considered. TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .We have added this sentence in the Study limitations subsection (Lines 490-497): Finally, it was better to complete the study by an interventional program in order to objectively measure the effectiveness of the intervention. 89 This method is particularly useful in situations where students start with a low-level of KoM, as it allows for a clear demonstration of progress and the effectiveness of educational strategies aimed at improving awareness and understanding of misconduct. 89 By assessing students' KoM before the program (pre-test) and after its completion (post-test), it was possible for the authors to determine the extent of learning and the impact of the intervention on our students' KoM. COMMENT Fourthly, we had shown in our study that plagiarism is also related to limited language ability. The questionnaire is in French. The questions, I guess, are unintentionally measuring language ability. That had to be checked by a language test score. RESPONSE .First, it was unclear for the reviewers to understand what the reviewers mean by “our study”. For that reasons, we performed several research and we retained some references where “Gezgin UB” was cited as an authors. We found the following 3 papers: 1.Perkins M, Gezgin UB, Roe J. Reducing plagiarism through academic misconduct education. Int J Educ Integr. 2020 2020/05/01;16(1):3. 2.Perkins M, Gezgin UB, Roe J. Understanding the Relationship between Language Ability and Plagiarism in Non-native English Speaking Business Students. Journal of Academic Ethics. 2018 2018/12/01;16(4):317-28. 3.Perkins M, Gezgin UB, Gordon R. Plagiarism in higher education: classification, causes and controls. Pan-Pacific Management Science. 2019;2:3-20 .We have also found 3 other interesting papers: 1.Holm S, Hofmann B. Investigating the Reliability and Factor Structure of Kalichman's \"Survey 2: Research Misconduct\" Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral Students in Scandinavia. J Empir Res Hum Res Ethics. 2017 Oct;12(4):199-205. PubMed PMID: 28707501. Epub 20170714. 2.Jereb E, Perc M, Lämmlein B, Jerebic J, Urh M, Podbregar I, et al. Factors influencing plagiarism in higher education: A comparison of German and Slovene students. PLoS One. 2018;13(8):e0202252. PubMed PMID: 30096189. Pubmed Central PMCID: PMC6086479. Epub 20180810. eng. 3.Patil VL, Ganganahalli P. Perception of Plagiarism Among Medical Postgraduate Students: An Observational Study. Cureus. 2024 Jul;16(7):e64513. PubMed PMID: 39139346. Pubmed Central PMCID: PMC11320932. Epub 20240714. eng. .We have added some of these references in the manuscript. .Concerning your remark, we have consulted your paper (Perkins M, Gezgin UB, Roe J. Understanding the Relationship between Language Ability and Plagiarism in Non-native English Speaking Business Students. Journal of Academic Ethics. 2018 2018/12/01;16(4):317-28.), and we agree with the reviewers that English language ability is one of the main reasons why students commit plagiarism offences. We have noted that the authors of the above-cited paper reported statistically significant differences in the English language abilities of students who have previously committed plagiarism offences, compared to students who have not. However, this is not the case in Tunisia, since the questionnaire was in French, and French is the second language in Tunisia and medical teaching is in French TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .We have considered your remark as a study limitation, and we have added the following reference: Perkins M, Gezgin UB, Roe J. Understanding the Relationship between Language Ability and Plagiarism in Non-native English Speaking Business Students. Journal of Academic Ethics. 2018 2018/12/01;16(4):317-28. .Please see lines 486-490: Eighthly, it was better to check the students’ language ability, since they often claim that English language ability is one of the main reasons why they commit plagiarism/misconduct offences. 88 Some authors reported statistically significant differences in the English language abilities of students who have previously committed plagiarism/misconduct offences, compared to students who have not. 88 COMMENT Finally, we need to consider the fact that the participants are dentistry students. It would have been better to design the questions relevant for their subject area. In this form, the questions are too far away from the realities of plagiarism. RESPONSE .Thank you for your excellent remark .Again, we have added the reviewers’ remark as a study limitations TEXT INSERTION (IF APPLICABLE)/ PAGE/ LINE NUMBER OF CHANGE .Taking into account the remarks of the first reviewers (Remark N°1), we have added the following paragraph inside the paper (Lines 161-175): Why we have chosen the Laval University quiz 23? While various tools have been established and recommended to assess plagiarism, particularly in terms of, attitudes, acceptance, and practice, 16 , 23 , 24 , 35 , 40 - 44 evaluating KoM is also important, especially among PGDSs. Assessing KoM helps promote academic integrity, ensures ethical research practices, cultivates critical thinking skills, and enhances the quality and originality of scholarly work. Our study appears to be the first to apply a virtual quiz to assess students’ KoM. 35 We opted for the Laval University quiz 35 to evaluate KoM among Tunisian PGDSs for several reasons. First, the quiz was previously used in a local study involving UHDs. 4 Second, all available surveys used to assess understanding; attitudes, practices, and knowledge related to plagiarism were in English and lacked a certified French version. 16 , 23 , 24 , 40 - 44 Since French is the second language in Tunisia, and since medical teaching is in French, the French Laval quiz appeared to be more suitable for Tunisian PGDSs without the need for translation or validation. Third, the Laval quiz 35 is not time-consuming, requiring thoughtful responses, with an average of 15 minutes needed to answer the 11 questions. .The following sentence was added in the study limitations subsection (Lines 459-461): Thirdly, considering the fact that our participants are dentistry students, it would have been better to design the questions relevant for their subject area. In the Laval quiz 35, the questions can be considered “far away” from the realities of KoM. COMMENT Thus, for these reasons, I think this paper should not be indexed. RESPONSE .While we respect your point of view and your decision at this stage, we have significantly improved the scientific quality of our paper, which includes (as any scientific paper) some limitations. However, we have previously published a similar paper including university hospital doctors (see Khemiss M, et al. Understanding of plagiarism among North-African university hospital doctors (UHDs): A pilot study. Account Res. 2019 Feb;26(2):65-84. PubMed PMID: 30572716. Epub 20190110. Eng). The latter paper was cited 9 times (Scopus). .In brief, we respect your point of view, and we which that you change it taking into account the effort we performed to revise our paper. COMMENT Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? No Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes RESPONSE .Thank you. .We have noted that we received 4 YES (67%) and 2 NO (33%)"
}
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}
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https://f1000research.com/articles/13-415
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https://f1000research.com/articles/12-378/v1
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06 Apr 23
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{
"type": "Research Article",
"title": "Characterization of sacha inchi (Plukenetia volubilis) and taro (Colocasia esculenta) flours with potential application in the preparation of both gluten-free and high protein foods.",
"authors": [
"Ruby Aracely Narváez Cadena",
"Angie Paola Salas Zambrano",
"Jesús Eduardo Bravo Gómez",
"Karen Sofia Muñoz Pabon",
"Diego Fernando Roa-Acosta",
"Ruby Aracely Narváez Cadena",
"Angie Paola Salas Zambrano",
"Jesús Eduardo Bravo Gómez",
"Diego Fernando Roa-Acosta"
],
"abstract": "Background: Interest in alternative sources of tubers and legumes has increased in recent years because of the constant search for raw materials that provide bioactive compounds with antioxidant potential benefits for consumers. The functionality of new raw materials is sought through physical and/or chemical modifications to develop and innovate new foods. The objective of this study was to characterize taro (TF) (Colocasia esculenta) and sacha inchi (Plukenetia volubilis) flours, obtained by the wet (SIF-WM) and defatted method (SIF-DM), as an alternative for the formulation of new functional foods. Methods: The free polyphenols of the different mixtures were analyzed, and the antioxidant properties of the extracts obtained were measured using ABTS.* (2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). The ABTS radical method, which reacts with the phenolic compounds of the food matrix, using Trolox as a standard. The blends were subjected to pasting analysis, flow profile tests, determination of viscoelastic properties (temperature sweep). Characterization of common microorganisms in these foods was performed. Results: The highest protein value was obtained in the sacha inchi flour obtained by the defatted method (72.62). The majority of components in taro were carbohydrates (85.4%). About antioxidant and determination of free polyphenols, taro flour obtained values of 2.71 µmol ET/g and 7.47 mg EAG/g, higher than Sacha inchi flours. In the rheological analysis (pasting properties, flow profile, and viscoelasticity), we observed that adding taro flour in different mixtures increases the viscosity peak and a lower breakdown, while there was an increase in setback. Except for defatted sacha flour, the others presented a flow index >1 before heating, showing a dilatant fluid behavior. The presence of Taro flour improves gel formation and stability. Staphylococcus aureus and Salmonella were present in the taro flour. Conclusions: The flours analyzed represent a raw material with great potential for the development of gluten-free foods with functional properties.",
"keywords": [
"Rheology properties",
"Proximal composition",
"Microbiological quality",
"Gluten-free foods"
],
"content": "Introduction\n\nAccording to Ref. 1, in 2050, if economic growth is low, governance performance is weak and food demand is very high, driven by rapid population growth, a high intensity of land use will be required, leading to an expansion of crops to meet demand, under these conditions food insecurity is likely to worsen, especially in developing regions. Improved access to resources and a growing population can generate a high demand for food, especially for meat and dairy products.2 These changes in livestock production are environmentally unsustainable, due to the demand for resources such as the use of land to produce crops needed for animal feed and fresh water; furthermore, animal production is associated with the generation of greenhouse gases, a situation that contributes to the acceleration of global warming.3 The consumption of meat and dairy products are important sources of protein, vitamins, and minerals in the human diet.2\n\nIn this scenario, we must design food systems to contribute to global environmental sustainability and meet nutritional needs, proposing diets based on plants that allow including adjustments according to each region coupled with cultural customs.4 Underutilized or orphan crops are used to design original foods, not aimed at international trade, however, because of their high adaptation to the local environment, these crops play an important role in regional nutritional security.5 The mixture of plants such as cereals, pseudocereals, legumes, tubers, among others, are used to create different products with adequate balance of protein, carbohydrates, fiber and micronutrients such as vitamins and minerals.\n\nFor example, Sacha inchi (Plukenetia volubilis) known as wild peanut, Inca peanut, sacha peanut or mountain peanut, is an oleaginous plant that belongs to the Euphorbiaceae family.6 Today, Sacha inchi is still cultivated in the lowlands of the Peruvian Amazon and has been planted for centuries by the indigenous population.7 In Colombia, according to Ref. 8, production exceeds 2,400 tons of Sacha Inchi seed. The department of Putumayo is the largest producer of sacha inchi with 282 hectares, followed by Valle del Cauca, Caquetá and Antioquia.\n\nSacha inchi is a promising and industrializable food native to the Amazon that has essential unsaturated fatty acids such as omega-3, as alpha-linoleic acid with 47.7% to 51.9% and omega-9 as oleic acid with 7.9 to 8.9% by weight of oil, 27.4% protein, 4% ash and about 50% oil.9 These nutritional properties make sacha a favorable food for health and a suitable crop for developing high-protein and gluten-free foods.\n\nTaro is a tuber abundant in starch of which 17-28% is amylase and the remaining is amylopectin.10 Taro has a high content of resistant starch that allows slow digestion with valuable effects on cholesterol and blood glucose regulation.11 Taro has a high carbohydrate (59.36%) and protein (24.99%) content, the mineral content of Taro, the mineral present in the highest amount is magnesium 242.373 mg/kg, followed by calcium 94.455 mg/kg, iron 8.351 mg/kg and zinc 6.210 mg/kg, and vitamin C 0.188 mg/100 mg, vitamin B1 0.047 mg/100 mg, and Vitamin B3 0.078 mg/100 mg.12 Compared to other tubers such as sweet potato, potato, cassava and yam; taro has a higher protein and fat content.12 Likewise, Taro has flavonoids and phenolic acids that have antioxidant properties; flavonoids, the largest group of phenolic compounds identified in the whole plant, are associated with reducing many degenerative diseases.11\n\nFoodstuffs are complex systems of great nutritional richness and therefore sensitive to attack by microorganisms (bacteria, fungi and yeasts). The main mode of contamination of raw materials is animal defecation, manure fertilization and recontamination persisting in facilities and transport; in addition, insects and rodents are a source of contamination.13 The low water activity (aw < 0.60) of meal does not favor microbial growth; however, contaminating spores along with inactive microorganisms will remain viable for prolonged periods and constitute a potential health hazard. As a persistence mechanism, Salmonella and other pathogens form biofilms that protect against disinfection and increase their tolerance to drying processes.13\n\nIn food matrices there is always a microbial load that must not exceed certain limits, according to Colombian regulations, which must be controlled to avoid the deterioration of the product and the consequent loss of its quality and suitability for consumption.\n\nThe design and production of new foods that respond to food and nutritional security amid climate change in low-income countries is a challenging issue, so this study aimed to characterize the chemical, microbiological, rheological and bioactive properties of Taro and sacha inchi flours as potential foods applied in the formulation of different foods.\n\n\nMethods\n\nThe taro tubers were bought in the Municipality of Orito Putumayo, located at 0° 38′ North Latitude and 76° 37′ West Latitude of Greenwich. Average temperature of 25°C and relative humidity of 88%. The fresh Sacha inchi almonds were supplied by the company Fruty Amazónicos S.A.S. located in the village of La Concordia in the municipality of Valle del Guamuez, located at 00° 25″ north latitude and 76° 54″ west longitude. Temperatures range between 27°C and 40°C.\n\nThe taro flour (TF) was obtained following the methodology of Ref. 10. The raw material was received, the peel was removed; it was washed to eliminate impurities and then the edible part was cut into slices to facilitate dehydration; then it was weighed on a FENIX Electronic Weight Only Table Scale to verify yield, subsequently it was dried in a rotary oven (ORVES, Colombia) at a temperature of 60°C for five hours to eliminate excess moisture. The dried slices were then ground in an electric mill (Quaker City Mill, model 4-e, Philadelphia) and then passed through a 30-mesh sieve system to achieve homogeneity in flour particle size.\n\nSacha inchi seeds were received in white kernel, i.e., without shell or husk. The flour was obtained using the two methods described below:\n\nWet method\n\nSacha inchi flour from the wet method (SIF-WM), was obtained as follows: wet milling was performed in a blender (Oster, BLST 4655, Colombia) of 1.25 L, to which the sacha inchi and water were added in a 1:3 ratio, this, in order to disintegrate the grain. Obtaining a milky and homogeneous suspension. In order to separate the insoluble extract (cake) from the water-soluble extract (milk), a cloth filter was used and then the cake was dried in an oven at a temperature of 65°C for 3 hours. Once dehydrated, it was immediately packed in a hermetically sealed polyethylene bag.14\n\nDefatted method\n\nThe sacha inchi flour from the defatted method (SIF-DM) was obtained as follows: the Sacha inchi kernel was placed in the hopper of the automatic tactile oil extraction press (CGLDENWALL, store model K28, Shanghai China), a temperature of 124°C was used. The press used the screw, which pushed the material into the main pressing cylinder, the pitch of the screw and the depth of the spiral were reduced, decreasing the volume available in the chamber, and the material being subjected to high pressure accompanied by friction against the closed bottom wall of the cylinder produced the extraction of the oil. The oil then flows through the existing orifices in the cylinder. The remaining material exits through the pressing system and the cake outlet nozzle.15\n\nThe proximate composition (protein, lipids, dietary fiber, ash and moisture) of taro and sacha inchi flours was determined according to the methods proposed by the AOAC (Association of Official Analytical Chemists, 1990)16 and the carbohydrate content was estimated by difference. The details of the method are explained in more detail in the protocols uploaded in the repository.\n\nWater activity measurement\n\nTo determine the aw of the raw materials, the powdered sample was placed in a Decagon Pawkit portable water activity meter until the cuvette was covered. Before reporting the measurement, the equipment was calibrated with standard salts at 0.25 (13.41 mol/kg LiCl 0.25 aw) and 0.76 (6.00 mol/kg NaCl 0.76 aw).\n\nProtein\n\nOn nitrogen-free paper, 0.2 to 0.8 g of sample plus 1 g of kjeldahl catalyst were weighed and placed in digestion tubes. 10 mL of sulfuric acid were added. Then, gentle heating was initiated until no foaming or splashing was observed, using a temperature ramp as follows: 125°C for 30 min, 270°C for 30 min and 400°C for 140 min.\n\nThe samples were digested until they were completely clear and translucent, free of organic matter, in the laboratory Kjeldahl digester (Raypa MBC-6/N, Spain).\n\nThen they were cooled to room temperature in the Raypa distillation unit, after which each sample was titrated with 0.1 N HCl.\n\nLipids\n\nFor lipid testing, 1 g of sample was weighed in the extraction cartridges, then 80 mL of petroleum ether was added, immediately transferred in the rack to the laboratory Soxhlet and Randall Extractor (SX-6MP, RAYPA, Spain). After the extraction time and solvent recovery, the samples were placed in an oven at 60°C for 1 hour to eliminate the remaining ether.\n\nFiber\n\nFor fiber testing, 1-2 g of the degreased sample were transferred to the laboratory fiber extractor (F-6P Fibertest, Spain) and fixed to the angle of the front part of the unit. Then 150 mL of 0.255 N H2SO4 was heated in an Erlenmeyer flask, when it was boiling, it was placed on top of the coolant, the heating knob was adjusted to boiling point 3 or 4 and left boiling for 30 minutes. At the end of this time, it was filtered and washed with distilled water and the operation was repeated 3 times using 30 mL of water each time. Then, 150 mL of sodium hydroxide solution preheated to 90°C was placed in the upper part of the cooler; it was brought to boiling and kept for another 30 minutes. Then it was filtered and washed three times with boiling water. The sample was then placed in an oven at a temperature of 100-110°C until a constant weight was obtained.\n\nThe determination of polyphenols was performed according to Ref. 17, with slight modifications. Two grams of the sample were weighed in a 50 mL falcon tube. The first fraction was added to the sample 8 mL of solution with 80% ethanol and 20% water and 1% formic acid (80 mL ethanol + 20 mL water + 1 mL formic acid). The samples were shaken for 25 minutes in a shaker at 200 RPM at room temperature. The samples were then centrifuged at 3500 rpm for 5 minutes at room temperature. Subsequently, the supernatant was taken in a new falcon tube (50 mL) and then 40 microliters of EDTA 2% was added to the supernatant.\n\nFor the second extraction, 8 mL of 70% acetone with 1% formic acid (70 mL acetone + 30 mL water + 1 mL formic acid) was added to the pellet of the first extraction. The pellet was shaken in solution for 25 minutes in the shaker at 200 RPM at room temperature. Subsequently, the samples were centrifuged at 3500 rpm for 5 minutes at room temperature and the second supernatant was poured into the first supernatant and mixed. Finally, the supernatant mixture was made up to 20 mL using distilled water and the absorbance was measured in the spectrophotometer (Thermo scientific, Genesys 10S UV VIS).\n\nIn a test tube 4 mL of ABTS (2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), solution was added and to start the reaction 135 μL standard solution and vortexed for 5 seconds. A reagent blank was carried with 4 mL of 4.5 acetate buffer and 135 μL of ethanol, point 0 was prepared by adding 4 mL of ABTS solution and 135 μL of ethanol. Finally, the tube was capped and waited exactly 30 minutes to measure the absorbance in the spectrophotometer (Thermo scientific, Genesys 10S UV VIS) at a wavelength of 729 nm.\n\nPasting properties\n\nThe pasting properties of each dispersion were determined using a rheometer (TA INSTRUMENTS, AR 1500, New Castel, USA), equipped with a starch pasting cell. Then, a suspension of flour in water with a concentration of 12% (w/w) in 25 g was prepared and exposed to heating and cooling. The following samples were analyzed: 100% TF; 100% SIF-DM; 100% SIF-WM; 25% SIF-DM: 75% TF; 50% SIF-DM: 75% TF; 75% SIF-DM: 25% TF; 25% SIF-WM: 75% TF; 50% SIF-WM: 75% TF; 75% SIF-WM: 25% TF. The shear rate was kept constant at 16.75 s-1, throughout the heating and cooling range (25°C-90°C-25°C) while the heating rate was 10°C/min. The following parameters were obtained from the rheological analysis maximum viscosity [Pa.s]; minimum viscosity [Pa.s]; breakthrough viscosity [°C] and setback viscosity [Pa.s]. Finally, using the Savistky-Golay function, the data were smoothed in the GraphPad Prism 8.0.1 program (RRID:SCR_002798).18,19\n\nFlow profile\n\nFlow properties were performed according to the methodology of Ref. 18 with modifications. An AR1500 rheometer (TA Instruments, New Castel, USA) was used in this study. The average viscosity was determined at 25°C for 12 min with a shear rate increasing in 4 steps as follows:\n\nStep 1: 1×10-3 s-1 to 1×10-2 s-1\n\nStep 2: 0.01 s-1 to 0.1 s-1\n\nStep 3: 0.1 s-1 to 1 s-1\n\nStep 4: 1 s-1 to 100 s-1\n\nSubsequently, the sample was heated to 90°C. Once this process was completed, the average viscosity was determined again at 25°C, subjecting the sample to the same shear rate.\n\nFlow curves (shear stress versus shear rate) were obtained and fitted to the power law model shown in Equation 1.\n\nWhere:\n\nT is the shear stress (Pa).\n\ny is the shear velocity (s-1)\n\nK is the coefficient of consistency (Pa. s-1)\n\nn is the flow behavior index\n\nThe flow behavior index indicates Newtonian flow behavior when n = 1, shear thinning behavior when n < 1 and shear thickening when n > 1). Consistency and creep were determined before and after heating in order to determine the effect of thermal processing on these parameters.\n\nDetermination of viscoelastic properties (temperature sweep)\n\nFor the determination of viscoelastic properties (temperature sweep) the method of Ref. 20 was used, the viscoelastic properties were determined in a rheometer (TA INSTRUMENTS, AR 1500, New Castel, USA) using a system of parallel flat plates, of 40 mm diameter and 1500 μm distance between plates. The edges of the plates were sealed with petroleum jelly, with the purpose of controlling evaporation and avoiding variations in concentrations of the aqueous suspensions used.\n\nThe samples were subjected to a cycle of dynamic heating (25-85°C), stabilization (85°C for 2 minutes) and cooling (85-25°C) at 10°C/min, with a frequency of 0.5 Hz and 0.5% deformation. The profiles of the viscoelastic moduli as a function of temperature were recorded using the equipment’s software.\n\nThe microbiological characterization of the flours was carried out, considering the methodology of a previous publication by the authors reported in Ref. 21, which was based on parameters established by the Colombian technical standard NTC that applies for each microorganism.\n\nTo perform the microbiological characterization, 10 g of sample were taken in triplicate, then diluted in 90 mL of peptonized water and mixed at 150 rpm for 10 min in a shaker (MaxQ 4450 orbital Thermo Ficher Scientific USA), following this, for each microorganism the seeding of the appropriate dilution and selective medium is described. The details of the method are explained in more thoroughly in the protocols uploaded in the repository https://doi.org/10.5281/zenodo.7582202.\n\nColiforms\n\n1 mL of each replicate was taken and seeded in a previously sterile Petri dish by seeding in depth on chromogenic colinstant agar for 24-48 h of incubation at 35°C.\n\nMesophiles\n\n1 mL of sample was taken from each replicate, and each dilution was seeded by immersion in previously sterile Petri dishes in Plate Count Agar (PCA) agar for 24-72 h at 30°C.\n\nFungi and yeasts\n\n100 μL of each replicate was taken and seeded per surface in previously sterile Petri dish by surface plate seeding on Potato Dextrose Agar (PDA) agar for 24-72 h incubation at 30°.\n\nBacillus cereus\n\n100 μL of each replicate was taken and surface seeded in previously sterile Petri dish by surface plate seeding on Mannitol egg Yolk Polymyxin agar (MYP) agar with egg yolk specific for Bacillus cereus for 24 h incubation at 37°C.\n\nStaphylococcus aureus\n\n100 μL were taken from each replicate and seeded per surface in a previously sterile Petri dish, by surface plate counting on Baird Parker agar at 24 h incubation at 35°C, and then incubated for 24 h at 35°C.\n\nSalmonella\n\n25 g of sample were taken in duplicate, then diluted in 225 mL of buffered pepton water and mixed at 150 rpm for 10 min in shaker (MaxQ 4450 orbital Thermo Ficher Scientific USA), once this time was over, they were left in incubation at 37°C for 18 h, after which 100 μL were inoculated in 10 mL of Rappaport Vassiliadis malachite green broth (RVS medium) at 41. Furthermore, 1000 μL were inoculated in 10 mL of Tetrationate Mueller Kauffmann broth (MKTTn medium) at 37°C for 24 h. After this time, the surface of a Petri dish containing XLD agar selective medium was seeded by means of a loop in such a way that asylated colonies were obtained, Salmonella Shiguella agar was incubated at 34°C for 24 h, at the end of which typical colonies of Salmonella spp. were observed.\n\nA completely randomized design was used to evaluate the rheological properties of native and formulated flours. The design was based on the type of flour and its inclusion levels in the formulated flours. The three inclusion levels were 25%, 50%, 75%. The response variables were viscosity as a function of temperature-shear rate and viscoelastic modulus (G′ and G″).\n\nThe results were presented as the mean ± standard deviation of triplicate experiments. One-way analysis of variance (ANOVA) was used to compare means. Differences between means were considered significant at P < 0.05 using Tukey’s new multiple range test. Data were subjected to analysis with Minitab version 20 (RRID:SCR_014483). Graphs were generated in Graphpad Prism 5.0 (RRID:SCR_02798).\n\nBoth statistical analysis and graph generation can be completed with Graphpad Prism 5.0. There are some open-source software that could be used to perform similar functions: Oracle SQL and Python (RRID:SCR_008394) using the Matplotlib library are two examples of similar software that may be used to perform similar functions required to repeat this study.\n\n\nResults and discussion\n\nTable 1 shows the results of the proximate analysis for the samples.56 Plukenetia volubilis seed on dry basis has a high lipid content (52.84%) like oilseeds such as soybean (16.61-24.71%), almond (Prunus dulcis) and 72,620,13 peanut (Arachis hypogaea) whose values vary around 50%.22,23\n\nThe acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method.\n\nValues are presented as mean ± SD. For each parameter, different letters indicate significant differences at p < 0.05.\n\nThe results of lipids are within the range of values reported by Refs. 24–27. The protein content of sacha inchi kernel (33.73%) is above the range, but close to the value reported by Ref. 25. As for ash, the value was 3.05%, crude fiber (3.71%), and carbohydrates (6.67%). Regarding moisture, sacha inchi seed presented a 6.62%, close to the value reported by Ref. 27 with 6.28%.\n\nTwo methods were used to obtain sacha inchi flour: the wet method and mechanical defatting.\n\nWet method: The flour obtained by the wet method had an oil content of 8.87% and a protein content of 31.54%, with a protein/fat ratio of 3.56.\n\nMechanical defatting method: the sacha inchi flour obtained by the mechanical defatting method had a protein content of 72.62%, being above the range of values reported by Refs. 24, 28–31 which vary between 41.49 and 65.6%.\n\nCrude fiber has a value of 7.71%, the carbohydrate content is 3.04%, below that reported by Ref. 28 with a value of 11.25%. This difference can result from suspended solids carried in the oil stream.\n\nThe comparison of the two methods for obtaining Sacha inchi flour (SIF-DM and SIF-WM) made it possible to see the method that presented the highest protein content was SIF-DM with 72.62% compared to a value of 31.55% for SIF-WM. The lipids results were close, 9.84% for the SIF-DM and 8.87% for SIF-WM. As for fiber, SIF-WM presented higher values (19.42%) compared to SIF-DM (7.71%).\n\nTaro flour: as shown in Table 1, carbohydrates are the major component of taro with a value of 85.42%. The values of protein (6.05%), ash (5.18%), and lipids (0.70%) from proximate analysis agree with research.10,32–36 Crude fiber is the only data below the range consulted with a value of 2.65%, the closest value being that reported by Ref. 36 with a value of 4.38%.\n\nTable 2 shows that the total polyphenols obtained in the flours are statistically different, taro flour presents the highest polyphenol content of 7.50 ± 1.73 mg EAG/ g, being like those reported by Ref. 37, in comparison with flours from other sources such as plantain (5.93 ± 0.43 mg EAG/ g)38 present a higher value. The defatted sacha inchi flour presented a polyphenol content of 3.37 ± 0.16 mg EAG/g flour, being higher than the flour obtained by the wet method, because the mechanical extraction involving pressure and temperature allows a release of phenolic compounds.39\n\nThe acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method; (FPP) refers free polyphenols.\n\nValues are presented as mean ± SD. For each parameter, different letters indicate significant differences at p < 0.05.\n\nRegarding the antioxidant activity measured by the ABTS method, taro flour obtained a statistically higher antioxidant activity with 2.71 ± 0.02 μmol ET/g compared to SIF-DM (0.49 ± 0.02 μmol ET/ g) and SIF-WM (0.71 ± 0.04 μmol ET/g). This difference can be explained because taro is a prime source of antioxidant compounds and, from a chemical point of view, has various biologically active phytoconstituents, such as flavonoids, sterols, and glycosides.40\n\nIn this study, a TF drying temperature of 60°C was used, which according to Ref. 41, temperatures between 50°C and 60°C allow for maximum antioxidant activities in taro flours. SIF-DM presented the lowest antioxidant activity because during extraction the oil stream carries away bioactive compounds, which in sacha inchi are present in essential fatty acids.42\n\nPasting curves\n\nThe viscosity profile was carried out to find the evolution of viscosity during the heating and cooling phase in the raw materials and each of the blends. According to the statistical analysis, the different flour blends significantly affect viscosity p < 0.05. Figure 1A shows the significant differences between the blends in the viscosity peak, where the presence of five different groups identified with letters from “a” to “e” are observed. In group “a”, the samples with the highest viscosity (25% SIF-DM:75% TF and 100% TF), and in group “e”, the samples with the lowest viscosity value (75% SIF-WM: 25% TF and 100% SIF-WM).\n\nThe data represent the significant differences in the values of: (A) viscosity peak [Pa.s]; (B) Trough [Pa.s]; (C) Breackdown [°C] and (D) setback [Pa.s]. The acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method. Values are presented as mean ± SD. For each parameter, different letters indicate significant differences at p < 0.05.\n\nAccording to the results, the samples with higher TF content present the highest viscosity peaks, due to the presence of starch contributed by TF, taking into account that in this study taro, presented 85.42% of carbohydrates that according to43 are represented by starch. Starch granules are not soluble in cold water, because of the strong hydrogen bonds that hold the starch chains together. Starch heated in excess water and above the pasting temperature suffers an order-disorder phase transition called gelatinization. This transition is associated with water diffusion into the granule, water uptake by the amorphous region, hydration, and radial swelling of the starch granules, resulting in an increase in viscosity. This positive correlation of starch content with peak viscosity is consistent with research on different commercial cereal, pseudo-cereal, root, and legume flours.44 Comparing SIF-DM flour with SIF-WM, the defatting method produces flour with higher viscosity, because of the interaction of water with proteins and starch,19 considering that SIF-DM has 72.62% protein.\n\nFigure 1B shows the significant differences in the samples behavior before the onset of retrogradation (trough or drop viscosity), which occurs at the end of the constant temperature section, before cooling begins. There are six different groups, identified with letters from “a” to “f”, where in group “a”, we have the samples with the highest trough value (25% SIF-DM: 75% TF and 100% TF), and in group “f”, the samples with the lowest trough value (75% SIF-WM: 25% TF and 100% SIF-WM).\n\nAccordingly, the samples that presented a greater viscosity drop are the ones with higher TF content, because of the alteration of the crystalline structure (amylopectin) that makes up the granules, causing an increase in the size of the granules and partial solubilization of the starch. It is possible that in mixtures where the presence of starch provided by taro is in greater proportion and the protein provided by the sacha inchi result in more free water for the starch molecules to swell and solubilize; however, at high protein ratios, the association between protein and starch granules could play a more important role, stabilizing the amylose leaching channel of starch granules and resulting in lower swelling power and solubility.45\n\nFigure 1C shows the significant differences in the samples behavior in the breakdown stage. According to Ref. 46, the breakdown or stability is the difference between the viscosity peak and the trough in the constant temperature section and shows disintegration at a maintenance temperature (95°C) during continuous shear; the lower the Breackdown value, the higher the anti-shear capacity. In this study, we observed six different groups, identified by letters from “a” to “f”. In group “a”, the samples with the highest breakdown value (25% SIF-DM: 75% TF and 100% TF), and in group “f”, the samples with the lowest value (100% SIF-WM). It was evidenced that the samples with low starch content contributed by taro present higher stability, while the samples with higher starch content have lower capacity to support viscosity during prolonged heating, because of the starch behavior, in which the low molecular weight amylose separates from the starch granule and they collapse at constant temperature until the amorphous part is solubilized, decreasing viscosity.47\n\nFigure 1D shows the significant differences between the mixtures in the setback parameter, where five different groups are identified by letters from “a” to “e”. In group “a”, we find the samples with the highest setback (25% SIF-DM: 75% TF and 100% TF), and in group “e”, the samples with the lowest values (75% SIF-WM: 25% TF and 100% SIF-WM). The variable reorganization or setback is the indicator of the retrogradation and rearrangement of starch molecules during the cooling process that defines the reabsorption of soluble starch polymers and insoluble granular fragments during the cooling phase.48 According to the results, blends containing lower taro content are less prone to retrogradation. As mentioned above, starch (amylose-amylopectin) contributed by TF with variations in temperature generates changes, e.g., amylose forms double helix associations of 40 to 70 glucose units, since amylopectin crystallization occurs by reassociation of the outermost short branches, i.e., both amylose and amylopectin are capable of retrogradation, although the amylopectin seems to be responsible for long-term quality changes in foods.49 In taro starch, amylopectin contents are higher than amylose 66 and 34 % respectively,50 which is the reason for attributing higher retrogradation in flour blends with higher TF.\n\nFlow profile analysis\n\nFigure 2 shows the results of the flow analysis with the viscosity behavior before heating (blue line) and after heating (red line) under stress conditions (shear stress, Pa) and shear rate (s-1). We observed the coefficients obtained by regression of the power model, where “n” is the flow index and “K” is the consistency index. According to the consistency index, we see that “K” increases in all samples except for SIF-WM, because of the viscosity gain, being “n” and “K” inversely proportional parameters.\n\nThe graphs show the flow profile behavior of: (A) SIF-DM; (B) SIF-WM; (C) TF; (D) 25% SIF-DM: 75% TF; (E) 25% SIF-WMH: 75% TF; (F) 50% SIF-DM: 50% TF; (G) 50% SIF-WM: 50% TF; (H) 75% SIF-DM: 25% TF; (I) 75% SIF-WM: 25% TF. The acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method.\n\nRegarding the flowability index, we observed the behavior of the samples with the highest starch content TF were those that presented the greatest change in “n”, decreasing their flowability index represented by the gain in viscosity attributed to the behavior of the starch in taro.\n\nRegarding the flow index, all the mixtures, except for SIF-DM, have a value of n > 1 before heating, showing that they have a dilettantish fluid behavior. In water and food starch suspensions, the dilatant or shear thickening behavior relates to the initial stiffness of starch granules to resist shear and to a high concentration of solids, resulting in particle swelling.51 SIF-DM presented an n of 0.7709, demonstrating a behavior of a pseudo-plastic fluid.\n\nFor the mixture’s behavior after heating, all the blends, except for SIF-WM, presented an n < 1, demonstrating a behavior of a pseudo-plastic fluid, i.e., that changes in temperature affect these mixtures behavior. This behavior occurs because, in the gelatinization process, the starch granules break, releasing amylose to the aqueous medium and, on cooling, these amylose chains align, forming networks that form gels or viscous suspensions.18 The n values for the SIF-WM were reduced to 1.064, exhibiting Newtonian behavior. The Newtonian flow shows that the viscosity is independent of the shear rate. According to Ref. 51, these flours could be suitable for formulating products such as beverages, where improving the nutritional content is required without affecting its viscosity during shearing.\n\nViscoelastic properties - Temperature sweeping\n\nFigure 3 presents the moduli G′ (red color) and G″ (blue color) as a temperature function (°C). We observe the behavior of the elastic and viscous moduli for each mixture, evidencing an increase in the moduli as the temperature sweeps are performed. Except for graphs “A” and “H”, the mixtures behavior during heating is similar, since the two moduli increase their value, decreasing the difference between them and achieving a crosslinking, where the material ceases to have a viscous character, i.e., it stops being liquid and becomes elastic properties characteristic of a solid. This behavior is characteristic of materials undergoing liquid-solid phase transformations. When the molecules gain weight, in this case, when the starch granules interlock, the loss modulus G\" decreases and the storage modulus G′ increases, reaching a point of equilibrium that is its material change of nature, its solidification.\n\nThe graphs show the loss modulus G″ and storage modulus G′ for: (A) SIF-DM; (B) SIF-WM; (C) TF; (D) 25% SIF-DM: 75% TF; (E) 25% SIF-WM: 75% TF; (F) 50% SIF-DM: 50% TF; (G) 50% SIF-WM: 50% TF; (H) 75% SIF-DM: 25% TF; (I) 75% SIF-WM: 25% TF. The acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method.\n\nThere is a progressive exudation of amylose in the swollen granules, where gel-like linkages are formed. Researchers have reported the effect of amylose to increase the firmness of gels during cooling as one of the initial causes of gel firmness. Thus, during the cooling stage, the moduli stay constant with the predominance of the elastic modulus.52\n\nThe behavior of flour blends A and H corresponding to 100% SIF-DM and 75% SIF-DM: 25% TF, respectively, shows that the G′ and G″ moduli remain constant both during the temperature increase and during subsequent cooling, thus presenting greater stability to temperature variations. This behavior responds to the low starch content of these samples, since starch is key for the viscoelastic behavior of the flours, due to the interaction with water, generating absorption and swelling of the granule and, consequently, greater viscoelasticity. SIF-DM and 75% SIF-DM: 25% TF blends did not present a gel point, however, the other blends presented a gel-like behavior, highlighting that the 50% SIF-DM: 50% TF and 25% SIF-DM: 50% TF blends presented the most elastic gel at a gel temperature of 60°C in both cases, showing similar viscoelastic characteristics.\n\nWe suggest an optimum level of protein inclusion represented by sacha inchi between 25 and 50%, where the consistency of the gel increases and mixtures prepared above this range do not present a gel point, while lower values will have a more liquid behavior.\n\nTable 3 shows the results of the microbiological analysis performed on the three types of flour. For the microbiological analysis, we considered the NTC 606953 standard for quinoa flours and NTC 26754 for wheat flour.\n\nThe acronym (TF) refers to taro flour; (SIF-WM) sacha inchi flour by wet method and (SIF-DM) sacha inchi flour by defatted method.\n\nAs can be seen in Table 3, the flours comply with the quality specifications required by Colombian regulations; however, Salmonella is present in the taro flour, possibly due to the persistence of this type of microorganism; drying this flour at 60°C preserves some bioactive compounds but is not sufficient to eliminate it. According to Ref. 14, this type of pathogens acquire resistance to disinfectants and temperature because they form biofilms, which protect them and can remain in equipment, utensils and facilities, contaminating food. In addition, flours such as taro can be contaminated during harvesting or transportation.\n\nTable 2 shows that in foods such as sacha inchi and taro flour, where aw is less than 0.85, Salmonella and other pathogenic bacteria such as Staphylococo can survive in a viable but non-culturable state for long periods of time due to their increased resistance to thermal processes.55 Although the growth of microorganisms is not maintained at low water activity, foodborne bacteria and fungi can easily contaminate flour and survive for long periods of time with a low reproduction rate.21\n\n\nConclusions\n\nThe method that allows for the highest concentration of protein in sacha inchi is mechanical defatting with a protein result of 73%, compared to that obtained by the wet method, which resulted in 31%. However, during the production of sacha flour with the mechanical method, bioactive compounds are lost, which is why lower values of total polyphenols and antioxidant activity are obtained, compared to taro flour.\n\nThe viscosity profile evaluation determined that the starch contained in taro provides good viscosity characteristics, being this an important ingredient for the development of foods such as creams, pastes, sauces, among others. However, mixtures with excess taro have a higher rate of retrogradation, presenting a disadvantage for food stability during storage.\n\nThrough the viscoelasticity analysis (temperature sweep), we found the optimum level of inclusion of defatted sacha inchi is between 25 and 50%, where a stable and consistent gel is presented.\n\nAlthough taro’s drying temperature of 60°C maintains polyphenols and antioxidant activity, it does not allow the inactivation of bacteria such as Salmonella, which has shown resistance to thermal treatment in recent years.\n\nDeveloping foods using gluten-free orphan raw materials, especially taro and sacha inchi that are easily adapted to regions with food safety hazards, can be a good alternative to offer the market different gluten-free products, excellent source of protein, and high fiber content.\n\nFuture research can formulate foods from sacha inchi flour, which will allow obtaining high protein foods, responding to the trend of obtaining high protein foods from vegetable sources.\n\nSalmonella contamination was present in the taro flour. In response, the facilities and equipment were washed and disinfected with a different product than usual, and again salmonella analyses were performed to guarantee its elimination.",
"appendix": "Data availability\n\nZenodo: Sacha_article, https://doi.org/10.5281/zenodo.7625871. 56\n\nThis project contains the following underlying data:\n\n- REOLOGY SAMPLES.zip\n\n• Flow profile analysis_folder containing data on the flow analysis of flours in different samples. (Folder contains data on flow analysis and statistical analysis of flours in different blends)\n\n• Pasting_containing curves and statistical data of pasting properties in different samples. (Folder containing curves and statistical data of pasting properties)\n\n• Viscoelasticity_containing curve data and statistical analysis of analyzed viscoelastic properties in different samples. (The folder contains the data of the curves and the statistical analysis of the viscoelastic properties analyzed)\n\nZenodo: Sacha_article, https://doi.org/10.5281/zenodo.7625871. 56\n\nThis project contains the following extended data:\n\nProtocols on proximate and microbiological analysis\n\n- Bacillus cereus--protocol for the determination of Bacillus cereus present in food according to the Colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Bacillus cereus according to Colombian regulations)\n\n- Coliforms--protocol for the determination of coliforms present in food according to the Colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Coliforms according to Colombian regulations)\n\n- Fungi and yeasts--protocol for the determination of fungi and yest present in food according to the Colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Fungi and yeasts according to Colombian regulations)\n\n- Mesophiles-- protocol for the determination of mesophiles present in food according to the colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Mesophiles according to Colombian regulations)\n\n- Salmonella Spp-- protocol for the determination of Samonella present in food according to the Colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Salmonella Spp according to Colombian regulations)\n\n- Staphylococcus aureus--protocol for the determination of Salmonella present in food according to the Colombian regulations is presented.docx. (This file contains the microbiology protocol for the determination of Staphylococcus aureus according to Colombian regulations)\n\n- Protocol Fiber--protocol for fiber determination is presented.docx. (This file contains the proximal analysis protocol for fiber determination and handling of the equipment used for this determination)\n\n- Protocol Lipid--protocol for lipds determination is presented.docx. (This file contains the proximal analysis protocol for lipds determination and handling of the equipment used for this determination)\n\n- Protocol Protein--protocol for protein determination is presented.docx. (This file contains the proximal analysis protocol for protein determination and handling of the equipment used for this determination.)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nWang X, et al.: Beyond land-use intensity: Assessing future global crop productivity growth under different socioeconomic pathways. Technol. Forecast. Soc. Change. 2020; 160(March 2019): 120208. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nRodríguez J, et al.: Caracterización fisicoquímica, funcional y contenido fenólico de harina de malanga (Colocasia esculenta) cultivada en la región de Tuxtepec, Oaxaca, México.2016; (no. 16): p. 47.\n\nYuan TZ, Liu S, Reimer M, et al.: Evaluation of pasting and gelling properties of commercial flours under high heating temperatures using Rapid Visco Analyzer 4800. Food Chem. 2021; 344(November 2019): 128616. PubMed Abstract | Publisher Full Text\n\nPang Z, et al.: Physicochemical properties and microstructural behaviors of rice starch/soy proteins mixtures at different proportions. Int. J. Biol. Macromol. 2022; 209(April): 2061–2069. PubMed Abstract | Publisher Full Text\n\nGui Y, et al.: The structural, thermal, pasting and gel properties of the mixtures of enzyme-treated potato protein and potato starch. Lwt. 2022; 154: 112882. Publisher Full Text\n\nKaur A, Shevkani K, Katyal M, et al.: Physicochemical and rheological properties of starch and flour from different durum wheat varieties and their relationships with noodle quality. J. Food Sci. Technol. 2016; 53(4): 2127–2138. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJozinović A, Šubarić D, Ačkar D, et al.: Influence of spelt flour addition on properties of extruded products based on corn grits. J. Food Eng. 2016; 172: 31–37. Publisher Full Text\n\nSandhu KS, Singh N: Some properties of corn starches II: Physicochemical, gelatinization, retrogradation, pasting and gel textural properties. Food Chem. 2007; 101(4): 1499–1507. Publisher Full Text\n\nJames EO, Peter IA, Charles NI, et al.: Chemical Composition and Effect of Processing and Flour Particle Size on Physicochemical and Organoleptic Properties of Cocoyam (Colocasia esculenta var. esculenta) Flour. Niger. Food J. 2013; 31(2): 113–122. Publisher Full Text\n\nGarcía-parra M, Polo-muñoz MP, Nieto Calvache JE, et al.: Physicochemical, rheological and structural properties of flours from six quinoa cultivars grown in Colombia. Front. inSustainable FoodSystems. 2022; 6: 1–10. Publisher Full Text\n\nPaulet PG, Bello-pérez LA, Salas F: Características viscoelásticas y estimaciones de masas moleculares en almidón de oca (Oxalis tuberosum). Rev. la Soc. Química del Perú. 2009; 75(2): 266–276.\n\nICONTEC: Harina de trigo. NTC 267.2007.\n\nICONTEC: Productos de molinería. harina de quinua. requisitos. Instituto colombiano de normas técnicas y certificación. NTC 6069.2014.\n\nSubedi S, Du L, Prasad A, et al.: Inactivation of Salmonella and quality changes in wheat flour after pulsed light-emitting diode (LED) treatments. Food Bioprod. Process. 2020; 121: 166–177. Publisher Full Text\n\nSofia K: Sacha_article. [Data]. 2023. Publisher Full Text"
}
|
[
{
"id": "195999",
"date": "04 Sep 2023",
"name": "Oluwaseun P Bamidele",
"expertise": [
"Reviewer Expertise Food Chemistry",
"Food processing and preservation",
"Encapsulation of bioactive compounds",
"Functional foods",
"Gamma irradiation."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI worked on the PDF format of this manuscript and there is a fundamental error in the design of this study. The work would have been good if the authors work on compositing the two raw materials. There is no scientific contribution with way the study is presented. Although the Sacha inchi is new but not Taro.\nThe major challenge with the manuscript is the design. Compositing the root (Taro) and the Sacha at different ratios or percentages will make a difference in flour, which is rich in protein and other bioactive compounds.\n\nAlso, the manner in which the author reported the analyses is poor. Reporting on Sacha is not enough, using it in food preparation will be the best.\nI recommend that the authors should proofread their manuscript. The English is not good enough.\nPlease find the annotated pdf with further comments here.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "10179",
"date": "09 Oct 2023",
"name": "Karen Muñoz",
"role": "Author Response",
"response": "The corrections suggested in the pdf of the manuscript were adjusted. A characterization of the two raw materials taro and sacha inchi is made. This research was done in order to pave the way for new projects on the development of food based on vegetable matrices. Mixtures with inclusion levels of 25, 50 and 75% of sacha inchi flour and taro 75, 50 and 25% were worked in order to evaluate the bioactive, rheological and proximal properties. We kindly request to specify the paragraphs or sentences that should be adjusted to improve the analysis. In addition, improvements were made in the English language."
}
]
},
{
"id": "175167",
"date": "04 Sep 2023",
"name": "Diego Salazar",
"expertise": [
"Reviewer Expertise Food Science and Technology. Research in new sources of foods",
"andean crops",
"legumes",
"tubers."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work presented is interested in using unconventional sources, their characterization, and their nutritional components. However, the work requires management of scientific writing, the information presented needs to be revised, and the correct use of units of measurement is missed, for example, %, degrees Celsius, among others. On the other hand, the methodology needs to be more precise and allow a straightforward reading of what has been developed. Finally, the results must be rewritten, and consider that critical analysis and discussion of the results must be carried out, not only using the data from the tables and rewriting them.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10180",
"date": "09 Oct 2023",
"name": "Karen Muñoz",
"role": "Author Response",
"response": "The units are adjusted and the methodology is clarified. We kindly ask you to specify in which paragraph it is necessary to adjust the analysis, since in each test a comparative and statistical analysis of the results is performed."
},
{
"c_id": "11200",
"date": "13 Apr 2024",
"name": "Karen Muñoz",
"role": "Author Response",
"response": "Thank you for your valuable comments. I would like to continue the process of evaluation and correction of the article, for this I ask for new corrections, in order to be able to make them. Best regards"
}
]
}
] | 1
|
https://f1000research.com/articles/12-378
|
https://f1000research.com/articles/13-1393/v1
|
19 Nov 24
|
{
"type": "Research Article",
"title": "Governmental expenditure and National development of Nigeria, 1990-2020: an empirical review",
"authors": [
"Abolaji Atobatele",
"Ahmed Moliki",
"Olusegun Olaoye",
"Daniel GBEREVBIE",
"Moyosoluwa Dele-Dada",
"Ahmed Moliki",
"Olusegun Olaoye",
"Daniel GBEREVBIE",
"Moyosoluwa Dele-Dada"
],
"abstract": "Background One of the main goals of the government is to ensure a development that would enhance the living standard of the people in the society. In this regard, capital expenditure that would promote infrastructure is most desired. However, in Nigeria, the government spends more on administrative cost (recurrent expenditure) than capital expenditure. Under such condition, contributions to economic growth and national development become an illusion.\n\nMethods This study employed Augmented Dickey Fuller Test (ADF) with Bound testing procedure, time series data that covers the period from 1990 to 2020 in Nigeria were used.\n\nResults The result from the analysis showed that governmental expenditure has a significant effect on the national development of Nigeria. All the variables have a long-run relationship with economic growth (RGDP), according to the ARDL model’s results. If the government poor policies on education, health services, and infrastructure etc. are addressed, in the long-run, Nigeria will achieve monumental development.\n\nConclusion The study adopted indices such as expenditure on Social and Community Services, Economic Services and Administrative Services to reflect the dynamics of government expenditure coupled with the yearly data garnered from the Central Bank of Nigeria spanning from 1990 to 2020.",
"keywords": [
"Administrative cost",
"government expenditure",
"economic growth",
"national development",
"Nigeria."
],
"content": "1. Introduction\n\nThe dogmatic belief that government should maintain law and order in order to promote society progress rather than interfere with economic growth was debunked with the advent of Neo-classical philosophy. This was the case up until the classical theory’s inability to allocate resources fairly resulted in the application of John Keynes’s Neo-classical principles. The primary argument put out by neo-classical theorists is that the government ought to become involved in the economy by providing monetary interventions to stimulate growth and help the country emerge from the Great Depression. As a result, many governments have expressed interest in their nations’ economic development and prosperity by allocating funds to raise the standard of living for their inhabitants in the areas of transportation, education, health, and agriculture.\n\nAgbarakwe and Anowor (2018) state that the classical apologists believed that the long-term management of the economy should rest with the forces of supply and demand, and that the government should not meddle in economic matters. The classical thinkers proposed a theory according to which the government should only uphold law and order and should not interfere with the market mechanism’s ability to function. Governments work hard to make sure that their citizens and residents have a comfortable life. This is especially true in the West, where the government provides basic necessities like high-quality, affordable housing, improved health care, agriculture, a well-developed road network, and so on. However, most third-world countries lack these efforts due to obvious factors like institutional weakness and the prevalence of corruption. Governments work hard to make sure that their citizens and residents have a comfortable life. This is especially true in the West, where the government provides basic necessities like high-quality, affordable housing, improved health care, agriculture, a well-developed road network, and so on. However, most third-world countries lack these efforts due to obvious factors like institutional weakness and the prevalence of corruption. Agbarakwe and Anowor (2018) claim that by assuming that the market would supply all necessary resources, the governments of the majority of third-world nations appeared to have endorsed the theory of the classical economics. It is clear that Nigeria’s administration adopted the ideas of classical economists by letting supply and demand dictate the requirements of the populace, which ultimately resulted in the monoculture of the nation.\n\nNonetheless, studies have shown a strong correlation between government spending and economic expansion. Keynes stated in 1936 that lowering interest rates and increasing government capital investment in infrastructure would encourage businesses to invest and be the cure-all for the economic crisis. Keynes (1936), Ram (1986), Ranjan and Shanma (2008), and Barro (1990) are among the academics who have claimed that more government spending on socioeconomic development promotes economic growth. According to them, an increase in government expenditure on things like health and education will lower production costs and boost labor productivity, which will boost firm profits and private sector investment and ultimately raise the country’s gross domestic product.\n\nEven though the country’s successive governments have tried to diversify the nation in accordance with Western demands, this idea has not produced any fruitful outcomes because Nigerian leaders are inherently corrupt and have not advanced socioeconomic development sufficiently to foster the kind of robust growth required for the nation’s development. Nigeria, according to Akpakpan (1998), was dependent on imports from other nations, particularly petroleum and agricultural supplies, for which she paid a premium. Thus, according to Akpakpan, the government had to launch intervention programs that will support Nigeria’s achievement of strong economic growth. The government intervened in the economy by launching programs under the Sustainable Development Goals (SDGs), such as the Cash Transfer Program, the Women’s Entrepreneurship Development Scheme, the School Feeding Initiative, and the Small Business Growth Program, to mention a few. These programs will foster real socio-economic development by giving citizens the necessary funds to launch profitable ventures that will raise their standard of living and assist the government in improving transportation, agriculture, education, and other areas that will spur economic growth. However, in spite of this, Nigeria has not experienced reasonable economic growth that will redistribute resources among its citizens.\n\nThe disparity between the rich and the poor continues to grow as a large number of Nigerians live in extreme poverty in comparison to the few wealthy Nigerians, who are primarily politicians. According to Vanguard (2021), The 2019/2020 Nigerian Living Standards Survey was released by the National Bureau of Statistics (NBS). It shows that 82.9 million people, or 40.1% of the country’s population, are living in extreme poverty. According to the survey, a higher proportion of Nigerians reside in rural areas, with slightly over 40% residing in metropolitan centers. This indicates that poverty is widespread in these areas. According to Knoema (N.D.), the national poverty headcount rate was 40.1 percent in 2018. In light of this, the study looks at how the government’s socioeconomic initiatives affect Nigeria’s economic expansion.\n\n\n2. Review of literature\n\nThis paper includes a conceptual review as well as an analysis of relevant empirical research on economic growth and socioeconomic intervention. This indicates that the concepts of growth and socioeconomic development are included in the conceptual literature evaluation.\n\nIn Rivers State, Nigeria, Agbarakwe and Anowor (2021) conducted a research titled “Government Intervention and Economic Development: Lessons from Songhai Development Initiative Farm.” In order to get the necessary data, it used a survey design that included questionnaires, interviews, and in-person observations. The hypothesis was also tested using chi-square. The study’s findings show a strong correlation between economic progress and the Songhai progress Initiative Farm. Therefore, it suggested that for the best results in terms of output, job creation, income, social welfare, and technical improvement, such and comparable government direct participation in the agricultural and other sectors should be encouraged. The study did not analyze its findings using the proper statistical method. Measurement of the difference, not the relationship, is done by Chi-Square. The application of Pearson Correlation will increase the study’s perceived value.\n\nAjide (2014) studied the factors that influence Nigeria’s economic growth. E-view was utilized in the study to analyze the findings. The study discovered that factors influencing economic growth include labor force participation, life expectancy, openness, and economic freedom. Accordingly, the research recommended cutting back on overbearing government intrusion while increasing funding for health and education. Anwana and Affia (2018) conducted a study titled Which Institutions Infrastructure Matter for Economic Growth and Development in Nigeria? We obtained time series data from the World Bank, Nigerian Central Bank, and other sources between 1986 and 2016. ECM was implemented, and a multiple regression model was used for data processing. According to the study’s findings, political, legal, and security institutions, as well as governance, have an impact on economic growth in Nigeria, whereas economic and regulatory institutions foster it. Accordingly, the study suggested that in order to maintain economic growth, the government should focus its policies on strengthening the financial, regulatory, and economic sectors of the economy; enhancing civil services and public infrastructure while shielding them from political influence; and bolstering civil liberties and the rule of law through the implementation of a strong security framework.\n\nIbietan (2011) conducted research on Nigeria’s agricultural and rural development policies from 1960 to the present. The study came to the conclusion that while incrementalism as a decision-making model is negative, it can help prevent policy reversals and somersaults by ensuring continuity in government policies and programs. To achieve a balance between the government and policy beneficiaries, the report suggested that the critical section and stakeholders in the policy-making process should work together. While our work examines the many efforts made by the government to ensure economic growth, the analysis is restricted to the numerous mechanisms utilized in agriculture. An evaluation of agricultural financing, policies, and initiatives for sustainable development in Nigeria in the twenty-first century: 1990–2014 was carried out by Fankun & Evbuomwan (2017). Using descriptive and inferential techniques, data for this study were collected from secondary sources, including Conference Journals and Publications, World Bank and United Nations publications, text books, Bullion, Annual Report and Statements of Accounts, Central Bank of Nigeria (CBN) Statistical Bulletins, and Bullion. The studies that were secondary were obtained through the use of descriptive and inferential techniques from the Central Bank of Nigeria (CBN) Statistical Bulletins, Annual Report and Statements of Accounts, Bullion, The Economic and Statistical Review of National Planning Commission, conferences, journals, and publications, as well as World Bank and United Nations publications and textbooks. According to the report, government support for agricultural initiatives is at a low point, making it impossible to guarantee that agriculture will contribute to sustainable development.\n\nA study titled Nigerian Socio-Economic Development: The Roles and Challenges of Small and Medium Entreprises Development Agency of Nigeria (SMEDAN) was carried out by Adegbuyi, Kehinde, Fadeyi, and Adegbuyi (2016). To wrap up its investigation, the study used a descriptive statistic. According to the report, among other things, SMEDAN suffers difficulties with insufficient funding, nepotism, tribalism, and a lack of awareness-raising efforts. If the researchers had used survey research, the study would have been more reliable. In order to alleviate poverty in Edo State, Nigeria, Igberaese and Dania (2015) conducted study on the assessment of socio-economic characteristics of community-based organizations. The study used random and purposive sampling strategies in a survey-style research design. The study discovered that CBO establishment is unstable over time, with membership ranging from 1 to 100 individuals, the majority of whom are involved in agricultural business. Therefore, the study suggested that the government take immediate action and provide them with interventions that will raise their standard of living. The notion of poverty was not sufficiently explored in this study.\n\nA study on Governance and the Challenge of Socio-Economic Development in Nigeria was carried out by Ojo, Aworawo, and Ifedayo (2014). According to the report, corruption has proliferated widely throughout Nigeria, impeding the establishment of good governance and, ultimately, negatively affecting the country’s socioeconomic progress. Therefore, the study suggested that if effective governance is to be implemented, Nigeria’s leadership should be corrupted. A study on The State, Governance, and Socioeconomic Development Realities in Nigeria was conducted by Ijere (2014). According to the report, corruption and poor governance are caused by ethnic chauvinism and historical accumulation in Nigeria. As a result, the report suggested that the rule of law, accountability, and openness be established.\n\nA study titled Economic Growth in Nigeria: Evidence from the Appraisal of Financial Sector Reforms and its Causal Effects was conducted in 2014 by Manasseh, Asogwa, Agu, and Aneke. Time series data were employed in the study, and the results were analyzed using E-view. According to the report, foreign direct investment and domestic credit provided by the banking industry are two important factors that can contribute to strong economic growth. According to the report, the government could offer a tax holiday and relax strict regulations that might deter banking institutions from lending to the private sector.\n\nA study titled Economic Development in Nigeria through the Agricultural, Manufacturing, and Mining Sectors: An Econometric Approach was carried out by Uzoigwe in 2007. Using the Engle-Yoo (1991) model, sectoral-econometric modeling was used in the study. The analysis discovered a substantial positive correlation between labor input and public capital expenditure for the growing sectors and the gross production of the manufacturing, mining, and quarrying industries. The study suggested that Nigerians choose leaders who possess a solid understanding of economic concepts.\n\nThe United Nations Development Programme (UNDP, 1992) asserts that human development ought to be the focus of development. The United Nations Population Fund (UNDP) emphasized the need for continued economic growth and income distribution to the majority of the population. The primary goal of human development is to ensure that everyone has access to the things that make life worthwhile, such as good health and affordable healthcare, education, and reliable transportation, all of which contribute to a respectable level of living. According to Uzoigwe (2007), political freedom, the provision of human rights, and individual self-respect are further indicators of human progress. The HDI is expressed by UNDP (1992) and includes component variables including high life expectancy, high literacy, and standard of living.\n\nThe national bureau of statistics (NBS) (2014) reports that between 1960 and 1969, Nigeria’s GDP per capita increased by 132%, and between 1970 and 1979, the growth rate peaked at 283%. However, from 1979 to 1983, there was a fiscal imbalance that had an adverse effect on the balance of payments due to high levels of inflation and a wave of unemployment that necessitated economic restructuring. The government of Nigeria implemented a thorough economic reform program in 1986 with the goal of structurally adjusting the country’s economy and improving its overall functioning. Thus, the Structural Adjustment Program (SAP) was implemented from 1988 to 1997, resulting in a 4% positive GDP growth and a 7% real GDP growth overall by 2010. Divergent opinions exist regarding the significant rise in government spending overall and the performance of the Nigerian economy over time. While some authors contend that there is little correlation between government spending and economic growth in Nigeria, others maintain that there is.\n\nIt is impossible to overstate the role that government expenditure plays in any economy’s expansion. Any economy, whether capitalist or socialism, needs to cooperate with the state apparatus in order to see strong economic progress. Though, as Nigeria’s example shows, government spending can lead to the misappropriation of public funds. According to Krueger (1990), government initiatives that involve state programs’ economic operations are ineffective and wasteful, and they can have a detrimental effect on a nation’s ability to develop economically. Smith (1776) asserts that states are thought to be the greatest misspenders of public funds. He emphasized further that people ought to be free to follow their dreams since they will eventually serve the interests of society as a whole. Keynes (1936) believed that in order to address the economy and lower unemployment, the authorities should use public expenditure as a tool of monetary policy sparingly. This calls for a comprehensive financial plan in which the government deliberately pursues a deficit budget by borrowing money rather than taxing the populace.\n\nPublic spending will have a multiplier impact that will control unemployment. Break (1982) emphasized that government spending should be multifaceted since no economy has ever reached a stable stage of development without the involvement of the government. The Keynesian theory describes how increases in spending over time can result in strong economic development. The 1930s economic downturn is when the Keynesian idea originated. He believed that raising government spending and lowering taxes would ensure that the recession would end and that each person’s purchasing power would rise. Anyebe (2015) asserts that the Keynesian theory is an essential safeguard against production and employment-related crises. Without a doubt, Keynes suggested ways to combat the crisis by raising spending and lowering taxes, which finally raised people’s purchasing power. According to Musgrave and Musgrave (1989), fiscal policy also directly affects demand by raising public spending and accelerating the expansion of the public and private sectors.\n\n\n3. Method\n\nThe study employed data from secondary sources. The information for variables like Gross Domestic Product (GDP) and Total Government Expenditure was taken from the CBN Statistical Bulletin, 2020. This times series analysis study spans a sample period from 1990 to 2020. This study estimated the effect of government spending on the transportation sector and economic growth using multiple regression models and econometric procedures. The following is the study’s model:\n\nFunctional relationship\n\nThe above functional relationship has been transformed into econometric linear models as follows.\n\nWhere:\n\nRGDP = Real Gross Domestic Product\n\nSOCOM = Expenditure on Social and Community Services\n\nECONS = Expenditure on Economic Services\n\nADMIN = Expenditure on Administrative Services\n\nUt = Error Term.\n\nGujarati (2004) pointed out that time series data are anticipated to be stationary, hence the Augmented Dickey Fuller (ADF) test was employed to verify the series’ stationarity as well as the order of integration.\n\n\n4. Discussion and Result\n\nTime series data were used in the study’s analysis. Testing the order of integration for the variables in time series data is the initial step, as recommended by Gujarati (2004). The most popular test is the Augmented Dickey Fuller (ADF) test, which was created in 1979 by Dickey and Fuller. The following is the mathematical model to verify the unit root:\n\nWhere ρ is the autoregressive process’s lag order, t is the error term, α0 is the intercept or constant, α1 is a trend term, and ∆ is the first difference operator. (See appendix Table 4.1 extended data presents the results of the ADF unit root).\n\nThe ADF Stationarity test’s decision rule states that if the ADF calculated value is less than the critical value, the null hypothesis that the variable has a unit root (non-stationary) is accepted; conversely, if the ADF calculated value is greater than the critical value @5%, the null hypothesis that the variable has a unit root is rejected. Because all of the variables’ ADF test statistics are only greater than the crucial value at the first difference, table 4.1 (Extended data) result showed that all of the variables are stationary at first difference rather than at level. The variables are all integrated of order I (1), according to this. (See Table 4.1 extended data) presents the results of the ADF unit root).\n\nThe Bound Test was run because series are integrated of different orders. In other words, they have combination of I (0) and I (1) Series. In order to find out if there is a long-run relationship amongst the variables, the Bound test was used as recommended by Pesaran, Shin, and Smith (2001) to determine whether there is a long-term association between the variables. We reject the null hypothesis, which states that there is no cointegration among the variables, because the F-Statistic is 13.73943, which is more than both 3.23 I (0) and 4.35 I (1) @ 5 percentage. We get to the conclusion that the variables have a long-term relationship.\n\nThe results of the bounds test indicated whether or not the variables are co-integrated. The ARDL Bound testing method was used to test this. If the F-statistic is larger than the upper bound I (1) of the critical value at the 5% level of probability, it is decided that there is cointegration or a long-term relationship between the variables; if not, the variables are not regarded as co-integrated and, consequently, no long-term relationship exists.\n\nno cointegrating equation\n\nH0 is not true\n\nDecision criteria: We can determine that there is cointegration, or a long-term relationship, if the computed F-statistic is larger than the critical value for the upper bound I (1). Finally, the test is deemed inconclusive if the calculated F-statistic lies between the lower bound I (0) and the upper bound I(1). If the F-statistic falls below the critical value for the lower bound I (0) bound, we conclude that there is no cointegration, and thus, no long-run relationship. Table 4.2 (extended data) displays an F-statistic of 13.74943, surpassing both the lower bound I (0) of 2.70 and the upper bound I (1) of 3.77 at the 5% significance level. It follows that cointegration exists. Stated differently, the relationship is one of duration. (See Table 4.2 (extended data), the results of Bound test).\n\nAccording to Table 4.3 (extended data), the lag value of the coefficient RGDP (-1.841501) indicates that the present period’s adjustment speed of 184 % corrects the preceding period’s deviation from the long-run equilibrium. Additionally, in the short run, a percentage shift in SOCOM is linked, ceteris paribus, with a zero percentage decline in GDP. Similarly, ceteris paribus, a percentage change in ECONS corresponds to an average percentage gain in GDP. On average, ceteris paribus, a five percentage increase in GDP is linked to a % change in ADMIN.\n\nAmong the post-model tests conducted in this work are the Serial Auto Correlation Test, which verifies that the model’s residuals are normally distributed and free from the effects of serial (auto) correlation and the heteroscedasticity problem. All post-model tests that were performed, with the exception of Jarque Bera, which indicates that the data is not normally distributed, had P-values greater than 5% at the probability level, indicating the absence of serial correlation. Therefore, we tested for heteroscedasticity, and the outcome indicates that there isn’t any. The model underwent these tests to make sure it is trustworthy enough for economic forecasting. (See Table 4.4 (extended data), the summary of Post Model Estimation result).\n\nThe study examined the Governmental Expenditure and Economic Growth in Nigeria, 1990-2020: An Empirical Review with special reference to social and community service, economic service and administrative service expenditure in which all socio-economic activities fall under in Nigeria. The study, which was a time series analysis, made use of CBN statistical bulletin data from 1990 to 2020. Government social and community expenditure (GSOCOM) has long-run relationship with the economic growth (RGDP), according to the ARDL model’s results. In other word, there is a long-run effect between GSOCOM and Economic growth provided government changes its pattern of spending. The primary cause of the poor quality of education and health services is the government’s low spending on social and community service, which includes, among other things, education and health, compared to administrative functions like the National Assembly, security, etc. where billions of Naira is spent. As a result, Nigerians prefer to travel abroad in order to access these services, which has an adverse effect on the country’s foreign reserve and economic growth through leakages. A strong educational system and improvements in health care are enough to support rapid economic growth. More specifically, education along with effective institutional structures, robust macroeconomic policies, and improved public health are crucial tools for reducing poverty (Babatunde, N.D).\n\nAdditionally, government spending on economic services like road building and agriculture (GECONS) has a major beneficial long-run effect on economic growth. The Nigerian government is investing a lot of money in agriculture in an attempt to diversify the country’s economy. Farmers are given access to various packages designed to increase national food production and export the remaining food to other nations, which is contributing to economic growth. Additionally, the government is building and mending roads that will improve the quality of life for both citizens and investors in an effort to attract investment. For example, in order to promote trade, the government built sophisticated gauges from Lagos to Ibadan and Abuja to Kaduna. Other gauges were built all over the nation. For the real sector, infrastructure consists of intermediate goods and services, and for consumers, it consists of final goods and services. In order for Nigeria’s real sector to drive growth and development, infrastructure needs to receive sufficient attention. Supporting this view are Nedozi, Obasanmi, & Ighata, (2014) furthermore, infrastructure contributes to macroeconomic stability and enhances quality of life by providing utilities like transportation, energy, and communication services.\n\nLast but not least, there is a strong positive correlation between economic growth, the National Assembly, and government spending on administrative services (GADMIN). The federal government of Nigeria has invested enormous sums of money in the National Assembly and other administrative duties since the country’s enshrinement of democracy in order to enshrine good governance. In addition, the government has spent a lot of money on security over the previous seven years in the fight against terrorism. The economy of Nigeria will benefit from direct investment if terrorism and other antisocial behavior are eradicated. The study’s consideration of government expenditure components (general administration, defense) is crucial in understanding Nigeria’s economic growth; the country’s political system has no appreciable bearing on the country’s economic growth. Additionally, general administration has a major and favorable impact on Nigeria’s economic progress. This suggests that higher spending on general administration will probably lead to higher economic growth rates. Additionally, if every naira allocated for this index is spent prudently, this will accomplish its goal. (Amakor & Echomeba).\n\n\n5. Conclusion and Recommendations\n\nIn line with J. Paul Dunne & Nan Tian’s (2013) findings on military expenditure, economic growth, and heterogeneity, which showed that military expenditure has a negative effect on economic growth, capital expenditures on health have a positive impact on GDP but have little relationship to economic growth. Additionally, ongoing expenditures on public safety (defense) had a negligible and negative impact on economic growth. The overall or aggregate effect of government spending on economic growth, however, is statistically significant. This finding adds support to Ukpabi Nnamdi’s (2013) empirical analysis of the relationship between government spending and economic growth, which shows that government spending promotes economic growth. The Keynesian (1936) theory of government active economic intervention through the use of diverse policy tools is further supported by this. Additionally, the research confirms Wagner’s (1813) premise of Ever Increasing State Activity because the CBN data on government spending and GDP show an increasing tendency. As a result, our analysis adds credence to the mounting body of evidence showing that government spending influences economic growth and is correlated with it. The study goes on to say that the elements of government spending that were taken into account—general administration, defense, education, and health—are crucial factors in explaining Nigeria’s economic growth and that the country’s political system has no appreciable bearing on it.\n\nTherefore, the study recommended that the government increase funding for social and community service in order to provide citizens with high-quality, reasonably priced health and education services that include access to cutting-edge medical facilities. This will help to end medical tourism abroad and create a skilled labor force that leads a healthy lifestyle and will support the nation’s economic growth. Consequently, increasing funding for social and community services will contribute to the ability to experience sustainable economic growth. It was also suggested that additional funding be given to administrative services, particularly security. The government must ensure that the military equipment required to fight terrorism is acquired and put to use. Additionally, the government ought to cut back on funding for the national assembly in order to redirect the extra funds to the health and education sectors, all of which will significantly boost economic growth.",
"appendix": "Data availability statement\n\nThe data used in this study can be accessed online from https://www.cbn.gov.ng/documents/statbulletin.asp\n\nFigShare: The result from the e-view. http://doi.org/10.6084/m9.figshare.27324417.v1 (Atobatele, 2024).\n\nThis project contains the following data:\n\n- flashare result.docx (Table 4.1 to Table 4.4)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAdegbuyi AA, Kehinde OJ, Fadeyi OI, et al.: Nigerian socio-economic development: The roles and challenges of small and medium entreprises development agency of Nigeria (SMEDAN). 3rd International Conference on African Development Issues (CU-ICADI 2006). 2016.\n\nAgbarakwe UH, Anowor OF: Government intervention and economic development: Lessons from Songhai development initiative farm in Rivers State, Nigeria. International Journal of Economics and Financial Research. 2018; 4(1): 13–21.\n\nAjide K: Determinants of economic growth in Nigeria. CBN Journal of Applied Statistics. 2014; 5: 2.\n\nAkpakpan EB: Economics beyond demand and supply. Belpot Nig. Co. Abak; 1998.\n\nAnyebe AA: A reflection on public enterprise sector in Nigeria. International Journal of Sustainable Development. 2015; 4(4): 348–358.\n\nAtobatele A: The result from the e-view. figshare. Figure. 2024. Publisher Full Text\n\nBabatunde MA: The relationship between health and economic growth in Nigeria. Paper delivered In memory of Late Dr Tajudeen Oladipo Busari.N.D..\n\nBarro RJ: Government spending in a simple model of endogenous growth. Journal of Political Economy. 1990; 98(5): S103–S125. Publisher Full Text\n\nBreak GF: Issues in measuring the level of government economic activities. American Economic Review. 1982; 72(2): 288–295.\n\nCentral Bank of Nigeria Statistics Bulletin: CBN statistical database.2021. Reference Source\n\nDickey DA, Fuller WA: Distribution of the estimators for autoregressive time series with a unit root. Journal of the American Statistical Association. 1979; 74: 427–431.\n\nEngle RF, Granger CWJ: Long-run economic relationships. Oxford: Oxford; 1992. Reference Source\n\nEngle RF, Yoo BS: Cointegrated times series: An overview with new results.Gujarati D, editor. Basic econometrics. 4th ed.1991. 2004. Reference Source\n\nE-View 9. Reference Source\n\nFankun DS, Evbuomwan GO: An evaluation of agricultural financing, policies and initiatives for sustainable development in Nigeria, in the 21st Century: 1990-2014. IOSR Journal of Economics and Finance (IOSR-JEF). 2017; 08(3): 32–38. Ver. III (May - June). e-ISSN: 2321-5933, p-ISSN: 2321-5925. Publisher Full Text Reference Source\n\nIbietan J: Public policy making process: Agricultural and rural development policy in Nigeria (1960 to date). International Journal of Studies in the Humanities. 2011; 8(9).\n\nIgberaese FI, Dania EN: Assessment of socio-economic characteristics of community based organizations in alleviating poverty in Edo State, Nigeria. International Journal of Development and Management Review (INJODEMAR). 2015; 10: 70–80.\n\nIjere TC: The State, governance and socioeconomic development realities in Nigeria. Public Policy and Administration Research. 2014; 4(1): 46–49.\n\nKeynes JM: The general theory of employment. Interest and Money. 1936. Reference SourceReference Source\n\nKnoema: Poverty headcount ratio at National Poverty Line.N.D..\n\nKrueger AO: Government failures in development. Journal of Economic Perspectives. 1990; 4(3): 9–23. ISSN 0895-3309 (Print) ISSN 1944-7965 (Online). Publisher Full Text\n\nManasseh CO, Asogwa FO, Agu DO, et al.: Economic growth in Nigeria: Evidence from the appraisal of financial sector reforms and its causal effects. IOSR Journal of Humanities and Social Science (IOSR-JHSS). 2014; 19(5): 01–10. Ver. II. e-ISSN: 2279-0837, p-ISSN: 2279-0845. Publisher Full Text Reference Source\n\nMusgrave RA, Musgrave P: Public finance in theory and practice. 5th ed.New Delhi: McGraw-Hill; 1989.\n\nNational Bureau of Statistics: Annual publications. Abuja: NBS; 2014.\n\nNedozi FO, Obasanmi JO, Ighata JA: Infrastructural development and economic growth in Nigeria: Using simultaneous equation. Journal of Economics. 2014; 5(3): 325–332. Publisher Full Text Reference Source\n\nOjo PO, Aworawo F, Ifedayo TO: Governance and the challenge of socio-economic development in Nigeria. Afe Babalola University Journal of Sustainable Development Law and Policy. 2014; 3(1): 132–148.\n\nPesaran MH, Shin Y, Smith RJ: Bounds testing approaches to the analysis of level relationships. Journal of Applied Economics. 2001; 16(3): 289–326. Publisher Full Text\n\nRam R: Government size and economic growth: A new framework and some evidence from cross-section and time-series data. American Economic Review. 1986; 76(1): 91–203.\n\nRanjan, Shanma: Government expenditure and economic growth: Evidence from India Icfa University. Journal of Public Finance. 2008; 6(3): 60–69.\n\nSmith A: The wealth of Nations. London: 1776.\n\nUNDP: United Nation Development Programmes (UNDP) Publication. Washington DC: University; 1992.\n\nUzoigwe DC: Economic development in Nigeria through the agricultural, manufacturing and mining sectors: An econometric approach. Thesis submitted in partial fulfilment of the requirements for the degree of PhD (Economics) in the Faculty of Economic and Management Sciences at the University of Pretoria. 2007.\n\nVanguard: Poverty and widening inequality in Nigeria.2021. July 21. Retrieved from the internet on the 12th November, 2021. Reference Source"
}
|
[
{
"id": "342836",
"date": "04 Dec 2024",
"name": "Anthony Orji",
"expertise": [
"Reviewer Expertise Economics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nREVIEW OF THE PAPER:\n\nGovernmental expenditure and National development of Nigeria, 1990-2020: an empirical review\n\nOne of the main goals of the government is to ensure a development that would enhance the living standard of the people in the society. In this regard, capital expenditure that would promote infrastructure is most desired. However, in Nigeria, the government spends more on administrative cost (recurrent expenditure) than capital expenditure. Under such condition, contributions to economic growth and national development become an illusion. This study employed Augmented Dickey Fuller Test (ADF) with Bound testing procedure, time series data that covers the period from 1990 to 2020 in Nigeria were used. The result from the analysis showed that governmental expenditure has a significant effect on the national development of Nigeria. All the variables have a long-run relationship with economic growth (RGDP), according to the ARDL model’s results\n\nCOMMENTS\nThe authors should remove the span of years from the title, as it is unnecessary and could be presented more professionally. The author should cite papers up to 2024. The review of literature should be rigorous, analytical, integrative, argumentative and comparative. The background and the statement of the problem shout be made more convincing and motivating for the study. Use more recent stylized facts, statistics and figures to trace the problem and make the background more convincing. The theoretical literature and theoretical framework should be better developed. We need more clarity on the theories behind this study and the theoretical foundation of the chosen model. You need better justification on the choice of the model viz-a-viz other similar model that can also address these issues. Again, the variables used in the study were not properly described and justified. The paper has no model. For example, the authors made mention of bounds test but never specified an Auto Regressive Distributed Lag Model anywhere. This is quite appalling. The interpretation and discussion of the results should be properly situated in the literature and the economic content should be properly fleshed out.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "342834",
"date": "31 Dec 2024",
"name": "Uju Victoria Okoli",
"expertise": [
"Reviewer Expertise I have a doctorate degree in Development Economics therefore I believe I can assess this paper."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGenerally, the author did his best to address the research objectives. My observations will be discussed according to the sections contained in the paper.\nIntroduction: The repetition of the first citation of Agbarakwu and Anowor (2018) should be expunged because it made reading of the work a bit clumsy. Review of Literature: No theory was reviewed in this section only empirical literature. Also the empirical literature reviewed were not up to date. The literature should be updated to 2024 paper review. Human Development Index was brought up in section 2 without any prior mention of it in the introduction as one of the important variables to be studied under the research. I suggest that the author should effect this so that reading the research paper will progress sequentially. Method: The scope of the study was selected without justifying what informed the years that were included in the analysis. Also the study estimated the effect of government spending on the transport sector without informing the reader what gave rise to studying only the transport sector. Discussion and Result: The presence of co-integration gives room for carrying out the short run analysis. This was not so in this analysis and the interpretation was based on only the outcome of the ARDL bound test.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1393
|
https://f1000research.com/articles/13-1388/v1
|
19 Nov 24
|
{
"type": "Research Article",
"title": "Traditional opal mining practice in Ethiopia, challenges and its economic impact on rural households: the case of wollo opal mining",
"authors": [
"Tadesse Wudu Abate",
"Addise Zemelak Sisay",
"Addise Zemelak Sisay"
],
"abstract": "Background The discovery spurred further exploration, leading to the expansion of opal mining into neighboring districts. Numerous cooperative groups, composed of small-scale miners, traditionally explore, develop, and extract significant amounts of rough opal gemstones. This study tries to investigate the challenges and economic impacts of traditional opal mining practice in wollo province of Ethiopia.\n\nMethods The study used in this study is primary data collected from rural households, which are living in five districts of north wollo zone, in Amhara regional state. The data was collected using field observation, focus grouped discussion, interview, and questionnaire from sampled households. The study uses both descriptive and econometric methods of data analysis to achieve its objective.\n\nResults Among the challenges of traditional opal mining, primitive way of exploring and extraction, limited access to market and low institutional support in terms of training and finance are identified. The probit model reveals that, increased education, access to training, and access to credit positively influence the likelihood of engaging in opal mining. The ESR model shows that, the average treatment effect on the treated (ATT) indicates that participating in opal mining increases monthly income by 31,380 ETB, while the average treatment effect on the untreated (ATU) shows a potential income increase of 31,625 ETB for non-miners if they engaged in mining.\n\nConclusion The study identifies three main categories of challenges faced by traditional opal miners: exploration and extraction issues, market limitations, and regulatory and institutional shortcomings. Exploration and extraction challenges include the lack of modern mining tools and knowledge, as well as difficult terrain, leading to inefficient and hazardous mining practices. Market-related challenges involve limited access to broader markets and lack of value addition, resulting in miners selling raw opals at significantly lower prices compared to polished ones.",
"keywords": [
"Challenges",
"Economic impact",
"Endogenous Switching Regression Model",
"Wollo Opal",
"Ethiopia"
],
"content": "1. Introduction\n\nEthiopia’s volcanic formation present significant opportunities for the extraction of metallic minerals, industrial minerals, and rocks and gemstone resources (DEJENE, 2015). Amhara Mines agency has identified the occurrence of various metallic minerals, industrial minerals and rocks, gemstone and energy resources in different parts of the region associated with volcanic rock (Ejigu, Ketemu, Endalew, & Assen, 2020). The Wollo plateau, part of northwestern Ethiopian Plateau, originated from the eruption of Ashange basalt, followed by the extrusion of Aiba basalts and Wogel Tena formation (Wireko-Gyebi, Puwurayire, Nyamekye, & Akudugu, 2023). These volcanic episodes were characterized by extensional tectonic settings of continental flood basalt, which are marked by presence of bimodal volcanic suites (Suryanarayana & Seid, 2022). Therefore, much of the mineral resources particularly peculiar gemstones are found associated with these volcanic rocks (Chauviré et al., 2023).\n\nThe Arstesian Opal Mining (ASM) is a common global practice for extracting base and precious minerals (Alves, Ferreira, & Araújo, 2021). Ethiopia is known by its traditional gold and gemstone mining from the biblical age and continues practicing up-to-date (Alves et al., 2021). In the history of opal trade, Ethiopian opals were once exported to the ancient Kingdom of Israel (Adesugba, 2018), which supports the notion that artisanal miners in Ethiopia have been extracting gemstone deposits for thousands of years. This indicates mainly the artisanal miners have mined the gemstone deposits in Ethiopia for several thousands of years. The mining sector contributes approximately 10% to the country’s foreign exchange earnings, with artisanal mining accounting for over 65% of this contribution (Krishnan & Bhatia, 2009). Additionally, it provides employment to about 1.26 million people and supports the livelihoods of over 7.5 million individuals in the country (Getaneh & Shikur, 2022; DEJENE, 2015).\n\nOpal mining in Ethiopia is particularly renowned in the Wollo province, specifically in areas such as Wegeltena, Dawunt, Meket, Wadla, Gazo, and Angot (see Figure 1). Since the discovery of play-of-color opal in 2008 near Wegel Tena, Wollo has gained international recognition as a significant source of this gemstone (Egunyu & Boakye-Danquah, 2024) The discovery spurred further exploration, leading to the expansion of opal mining into neighboring districts. Numerous cooperative groups, composed of small-scale miners, traditionally explore, develop, and extract significant amounts of rough opal gemstones. These miners control the distribution of rough opals, which are sold to gem dealers and eventually processed by cutters in Addis Ababa (Herrmann & Maas, 2022). The production of opals in Wollo has been notable, with over 1,500 kg of rough opal extracted by 2010. As a result, opal mining has become a vital source of employment and economic activity in the region, attracting traders and researchers alike. However, several challenges, such as inadequate mining techniques and poor infrastructure, continue to hamper the potential of artisanal opal mining in Ethiopia. (Katona & Krapf, 2020). Later on the discovery of opal resource expanded towards neighboring districts mainly Meket, Dawunt, Wadla, Gazo and Angot districts (Alemu, 2018).\n\nEthiopia’s mineral resources, particularly opals, play a critical role (Cartier, 2019) in its economic landscape. The discovery of high-quality opals in the mid-1990s and the subsequent breakthrough in 2008 positioned (Rondeau et al., 2012) Ethiopia as a strong contender in the global opal market, challenging the dominance of Australia (Mulaba-Bafubiandi, Ukponu, Odo, Singh, & Chauke, 2023). The opals from North Wello Delanta, known as Wello opals, are celebrated for their play-of-color and variety, leading to increased exports to major markets such as India, China, Europe, and the USA.\n\nEthiopia, renowned for its rich mineral resources, boasts a remarkable diversity of gemstones, with opals emerging as a key player in the trade sector (Dawes, 2020). The discovery of opals in the mid-1990s initially highlighted Ethiopia’s potential in this market, but it was not until 2008 that a significant breakthrough occurred (de Brito Barreto & Bretas Bittar, 2010). A substantial find of high-quality opal in North Wello Delanta, known as Wello opal, positioned Ethiopia as a serious competitor to the dominant Australian opal market. Wello opal, with its exceptional play-of-color and extensive color variations, quickly gained international acclaim, leading to a notable increase in exports to major markets including India, China, Europe, and the USA (George, Whitten, Metters, & Abbey, 2022; Herrmann & Maas, 2022).\n\nSmall-scale mining is central to Ethiopia’s opal industry, particularly in North Wello Delanta, where artisanal methods are prevalent (Onac & Forti, 2011). Despite the sector’s importance, challenges such as modernization and regulation persist (Milkias, Demissie, & Meshesha, 2023). In 2013, the Ethiopian Ministry of Mines, Petroleum, and Natural Gas proposed legislation requiring (Ofori, Takyi, Amponsah, & Gagakuma, 2023) that all opals be cut and polished domestically before export. However, this initiative faltered due to practical issues, including limited access to financing and a shortage of skilled lapidary workers (Palgutová & Štrba, 2022; SUORINENI, 2022).\n\nEthiopia’s vast mineral wealth, particularly its opals, is a cornerstone of its economic potential. The country’s journey from the discovery of opals to their prominence in the international market is both intriguing and complex, reflecting the broader trends and challenges in artisanal and small-scale mining (ASM). ASM practices in opal mining face numerous challenges, including the use of traditional mining techniques, low prices for unpolished opals due to the lack of local lapidary services, insufficient infrastructure, and inadequate financial and technical support. Despite these challenges, traditional opal mining has significantly improved the economic status of those involved.\n\nEthiopia’s mineral wealth is a cornerstone of its economic potential, with a notable array of gemstones contributing to its prominence in the global market. Among the diverse array of gemstones found within the country’s borders, opals have emerged as a significant asset but given little attention for its development. The journey of Ethiopian opals from their discovery to their status in the international market is both fascinating and complex, reflecting broader trends in artisanal and small-scale mining (ASM) and its impact on local economies (Wireko-Gyebi et al., 2023).\n\nThis research aims to explore the challenges and economic contributions of small-scale opal mining in Wollo, Ethiopia. By examining the economic impacts on local communities, the study seeks to provide insights into the sector’s role in regional development. This includes analyzing factors such as employment generation, income levels, and local economic activities that are directly or/and indirectly related to opal mining. Additionally, the research will address the challenges faced by miners and offer recommendations for improving the sustainability and profitability of small-scale mining operations.\n\nTherefore, the objectives of this research are\n\n✓ Analyzing the challenges of traditional opal mining in Wollo provinces\n\n✓ Investigating the economic impact of opal mining on the household in the study area.\n\nUnderstanding these dynamics is crucial for policymakers, stakeholders, and local communities to harness the full potential of opal mining while addressing the associated challenges. This study will contribute to the broader discourse on the role of small-scale mining in economic development and provide a case study that can inform similar contexts in Ethiopia and beyond.\n\n\n2. Review of related literatures\n\nOpal mining in Ethiopia commenced in the mid-1990s with the discovery of opal deposits in Shewa Province (Legasu & Chaubey, 2023). Initial assessments indicated that these opals did not match the quality of Australian opals (Dawes, 2020), which had long dominated the global market. Despite these early challenges, a significant breakthrough occurred in 2008 with the discovery of high-quality opals in North Wello Delanta (George et al., 2022). These opals, now referred to as Wello opals, exhibited exceptional characteristics, including a striking play-of-color and a broad spectrum of hues, quickly positioning them as strong competitors to Australian opals (Habte et al., 2020). This discovery revitalized interest in Ethiopian opals and underscored the country’s potential to emerge as a notable player in the global gemstone market (Kyngdon-McKay, Jorns, Wheat, Cushman, & Nemomissa, 2016).\n\nThe international demand for Ethiopian opal has risen, with major buyers located in China and the USA (Mustafa, Asfaw, Endris, & Bojago, 2023). However, this growing demand is accompanied by several challenges (Senior & Deveson, 2023). A primary issue is the spread of misinformation (Trickey, Lucifora, Wan, & Scott, 2013) regarding the qualities of Wello opals. Misconceptions associating Wello opals with the lower-quality Shewa opals have negatively affected their market value. This misinformation, combined with limited awareness and ineffective marketing (Senior & Deveson, 2023), has resulted in Wello opals being priced lower internationally than their quality would warrant (Ofori et al., 2023).\n\nThe Ethiopian government’s 40:60 rule mandates that a significant portion of opals be cut and polished domestically before export, aiming to promote local processing and add value to the gemstone sector (Katona & Krapf, 2020). However, this regulation has faced criticism. Many international buyers report that the quality of local cutting and polishing does not meet global standards, forcing them to purchase lower-quality stones at higher prices (Chauviré et al., 2023). Consequently, the rule has inadvertently imposed a financial burden on buyers who could otherwise process the stones more efficiently in their own facilities (Herrmann & Maas, 2022).\n\nThe growth and profitability of Ethiopia’s opal mining sector face several hurdles. The local lapidary industry struggles with skill deficiencies (Chauviré et al., 2023). Although some Indian traders have established cutting facilities in Ethiopia, the quality of local craftsmanship is often considered inadequate (Katona & Krapf, 2020). This reliance on external expertise from Jaipur has exacerbated costs and constrained the sector’s competitive advantage (Getaneh & Shikur, 2022). The 40:60 export rule, while well-intentioned, has not effectively fostered a robust domestic lapidary industry. The Ethiopian government’s emphasis on the size of rough and cut stones rather than their intrinsic qualities, such as play-of-color and clarity, has led to inflated valuations (Qin, Yi, & Zhang, 2024). Additionally, the complexities of the export process, including the requirement for foreign currency deposits in Ethiopian accounts, create further barriers for exporters (Legasu & Chaubey, 2023).\n\nThe domestic market for Ethiopian gemstones remains underdeveloped. The lack of local demand for opal jewelry, coupled with insufficient consumer and retailer knowledge about gemstones, poses a significant issue. The underdeveloped state of the domestic jewelry industry limits opportunities for local value addition. Illegal activities, including gemstone smuggling and unregulated lapidary operations, undermine the legitimate market (Egunyu & Boakye-Danquah, 2024). The presence of a black market for lower-quality gemstones affects the sector’s economic growth and poses challenges for law enforcement and regulatory agencies (Alves et al., 2021).\n\n\n3. Method\n\nThe target area is located in northern Ethiopia, Amhara regional state specifically ~550 km north of Addis Ababa, the capital city of Ethiopia (see Figure 1). Geographically UTM coordinates of 1284000N bound it to 1330000N and 501000E to 506000E latitude and longitude respectively. The area is accessible through Woldiya-Bahr Dar asphalted roads, and a number of gravel roads and footpaths generated by the local people and the administration. The north wollo zone has 13 rural districts and 5 urban city with diversified culture religion and climate. The zone is broadly classified in to lowland and highland districts based on alltitude. The target area of this study founds on the highland districts namely Wadlam Angot, Meket, Dawunt and Gazo (Habte et al., 2020).\n\nBoth exploratory and inferential research designs are used in this study. Since the challenges of opal mining in north wollo provinces are not studied yet, exploratory research design is applied to investigate the challenges that the traditional opal miners are facing. Inferential research design is applied to measure the economic impact of traditional opal mining on rural households. With this regard, mixed research design using both qualitative and quantitative methods of data analysis are applied. Descriptive and econometric methods of data analysis are also applied to investigate the challenges of economic impacts of traditional opal mining practices in wollo provinces (Dawes, 2020).\n\nThe type of data used in this study is primary data obtained from traditional opal miners of wollo provinces in Ethiopia in 2024. The methods used to collect those primary data are, field observation also known as the desk study, questionnaire and interview. To gather data relating with the challenges of traditional opal mining, field observation, desk observation, focus group discussion and interview are applied. Finally to address the economic impact of practicing traditional opal mining, semi structured questionnaire is distributed to the sampled households and relevant information is collected (Herrmann & Maas, 2022).\n\nThe study covers mining areas of north wollo zone including five districts of Gazo, Wadila, Flakit, Dwunit, and Angot. Multi stage and stratified sampling technique are applied to get the sampling units, which are rural households. First, out of the 13 districts found in the North-Wollo administrative zone, five districts namely Gazo, Wadila, Flakit, Dwunit, and Angot are selected purposively based on high access to opal minerals. Then households of those five districts are classified in to two strata of participants and non-participants of traditional opal mining practices. Finally, each respondents are selected using systematic random sampling technique. The sampling techniques applied so far is important to collect data that helps researchers to analyze the economic impact of traditional opal mining practice. In addition to this, to investigate the challenges of opal mining in the study are only those respondents who are engaging in opal mining are selected as follows. In the study area there are about fifth eight legal association engaged in opal mining practices and two individuals, the leader and the secretory of each association are selected and interview and discussion are held on the challenges they are facing at the time of mining and post mining challenges relating to market linkages.\n\nDetermining the sample size for a heterogeneous population often involves considering the variability within the population. For this purpose, we used Cochran’s formula, which is designed to provide a sample size that accounts for variability in a large population.\n\nWhere:\n\n• n0 is the sample size.\n\n• Z is the Z-score (the number of standard deviations a data point is from the mean) corresponding to the desired confidence level (e.g., 1.96 for 95% confidence).\n\n• p is the estimated proportion of the population that has the attribute in question (if unknown, 0.5 is used as it provides the maximum variability).\n\n• e is the desired level of precision (the margin of error).\n\nThe sample for finite population can be obtained from finite population correction factor formula as follows;\n\nWhere:\n\n• n is the adjusted sample size.\n\n• n0 is the initial sample size from Cochran’s formula given to be 384 for 5% margin error.\n\n• N is the population size.\n\nThis total sample is proportionally distributed to each districts based on their household size (as presented in Table 1).\n\nIn this study, we used two econometric models namely, the probit model and the Endogenous Switching Regression models. The first model, probit model uses to identify the determinants of households to participate in traditional opal mining and the second model, Endogenous Switching Regression model uses to investigate the impact of engaging in traditional opal mining on household income. Therefore, Logit and probit models are more appropriate for this type of binary dependent variable regression analysis. The different between the two is only the Cumulative distribution function they follows. By assuming the data used in this study to have a normal distribution, we prefer probit regression model which is specified as follows.\n\n3.6.1 The probit model specification\n\nHousehold status of being traditional opal miner is binary by its nature. Every household incorporates into two mutually exclusive groups of either being a member of traditional opal miner or being non-traditional opal miner.\n\nWhere,\n\n✓ yi is the opal mining participation status of household and given 1 if yes and zero if no\n\n✓ Xi are explanatory variables that can affect the household’s participation status\n\n✓ βi , represents the change in probablity of being opal miner when Xi changes\n\n✓ ϵi is the error or disturbance term of the regression model\n\n3.6.2 The endogenous switching regression model\n\nThe household participation in a traditional opal mining scheme is not random, as they self-select based on their perceptions of the benefits. Households choose to participant in opal mining only if they believe that they will received income in opal mining, which is higher than what they are actually obtaining agricultural practices.\n\nThe endogenous switching regression model tackles the issue by dividing individual household heads into different groups and examines the impact of these positions on outcome variable, which is annual income of households. The model consists of two components: the selection equation and the outcome equation. The selection equation focuses on the decision-making process or participation equation, while the outcome equation analyzes the relationship between the positions and the outcome variables.\n\nThe selection or participation equation is formed as:\n\nWhere I∗ is the latent variable, which is not observable and expressed as a function of some observed household and institutional characteristics?\n\nAs already seen in the above equation, Ii is a binary variable, which takes a value of ‘1’ for opal miners and ‘0’ for those who did not participate. Zi , represents factors that affect the participation decision and incorporates at least one explanatory variable which is not available in the regime equation. α , denotes the vector of parameters indicating the magnitude and direction of each explanatory variable’s effect on the decision to engage in opal mining practice. The residual ui captures the unobserved factors and measurement errors.\n\nThe outcome or regime equation on the other hand can be shown as;\n\nWhere, lnY1i and lnY2i are the natural logs of income for opal miners and non opal miners respectively which are determined by the exogenous variables Xji , β1 and β2 , are parameters that show the direction and strength of the relation between the outcome variable and the independent variables. In this research, annual income will be captured by household income (Y), lnY1i represents the natural logs of income for traditional opal miners and lnY2i represents the natural logs of income for non-opal miners groups.\n\nThe error terms of the above three consecutive equations (equations 1, 2 and 3) are assumed to have a normal distribution with zero mean and covariance matrix,\n\nwhere\n\nWhere,\n\n➢ σu2 , is the variance of the error terms in selection equation which is assumed to be one and coefficients are estimated up to a scale factor,\n\n➢ σ12 and σ22 are the variance of the error terms in the outcome equation and\n\n➢ σ1u and σ2u are the covariance of the participation equation and each outcome equation error terms.\n\nOn the other hand the * sign reflects the covariance of the error terms between each individual outcome equations since Y1iandY2i are not observed simultaneously.\n\nThe most important implication of the error terms structure is that, the correlation of error terms in the selection and outcome equations and their conditional expectation is non-zero\n\nUsing this information the maximum likelihood estimation can be developed as;\n\nAccording to Adesugba (2018), we can calculate the treatment effect on the treated, which is the main concern of policy makers, and it is the difference between the treated group and the counterfactual as well as the ATU as follows.\n\nThe base heterogeneity (BH1) for those households who are practicing traditional opal mining\n\nFor the group of households that who are not mining opal minerals, “the effect of base heterogeneity” is expressed as;\n\nFinally, the effect called “transitional heterogeneity (TH)” estimates whether the effect of traditional opal mining is larger or smaller for households that are not included in the group of Opal mining. The difference between ( Equation 7) and ( Equation 8) gives us\n\nThis equation measures the difference between households who are engaged in traditional opal mining and those who are not practicing the traditional opal mining. Is also measures what will be the income of traditional opal miners if they were not engaged in opal mining practice and at the same time, it will calculate the income of non-opal miner households if they engaged in opal mining practices.\n\nThe following table explained the variables, which determines the decision of households to engage to traditional opal mining. How those variables are measure, their nature of being continues or dummy and their expected signs to be positive or negative on the engagement of opal mining practice (see Table 2).\n\nThis study, titled “Traditional Opal Mining Practice in Ethiopia, Challenges, and Its Economic Impact on Rural Households: The Case of Wollo Opal Mining,” was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The research received ethical approval from the Research and Community Service Bureau of the College of Business and Economics at Woldia University on May 10, 2024, under approval number RCSTT/184/2024. The following ethical standards were adhered to throughout the research process:\n\n1. Compliance with the Declaration of Helsinki: The study was conducted in line with the principles of the Declaration of Helsinki, which emphasizes the protection of human participants, respect for their rights and dignity, and the promotion of well-being. This esearch prioritized participants’ health, welfare, and confidentiality.\n\n2. Informed Consent: All participants were fully informed about the objectives, methods, risks, and potential benefits of the study. Participation was voluntary, and verbal informed consent was obtained from each participant prior to their involvement. Participants were also made aware of their right to withdraw from the study at any time without consequences.\n\n3. Confidentiality and Data Protection: Personal data was handled in strict confidence. Participant identities were anonymized, and no personally identifiable information was disclosed in the final analysis or publications. All data were securely stored, and only the research team had access to them. Data protection protocols were followed to prevent unauthorized access.\n\n4. Non-Coercion and Autonomy: No participant was coerced or pressured into participating. Autonomy was respected throughout the study, and participants were encouraged to make informed decisions regarding their participation. The research ensured that vulnerable groups, such as women or economically disadvantaged individuals, were not subjected to any form of exploitation or undue influence.\n\n5. Protection of Vulnerable Populations: The study took particular care to protect vulnerable individuals. No minors were involved in this study.\n\n6. Minimizing Harm: The research team made every effort to minimize any potential risks or harms, both physical and psychological, to participants. Interview questions were designed to be non-intrusive, and participants were assured that they could skip any questions that made them uncomfortable. Should any participant experience distress, protocols were in place to provide support and discontinue the interview if necessary.\n\n7. Transparency and Feedback: Participants were informed about how the research results would be used and how they could access the findings if desired. The results will be disseminated to local communities, policymakers, and other relevant stakeholders, ensuring that the research findings contribute to improving the livelihood and economic well-being of rural households involved in traditional opal mining.\n\n\n4. Data analysis\n\nUnder this chapter, we analyzed data obtained from respondents using both descriptive and econometric methods. Additionally, we used qualitative and quantitate approaches to the objectives of the study. To address the objective of “investigating the challenges of traditional opal mining”, qualitative explanation of data obtained from field observation and discussion are applied. Additionally, we applied econometric method of data analysis to capture the economic impact of traditional opal mining on rural households using Endogenous Regression model, in addition to the probit regression model, which investigates the determinants of engagement in traditional opal mining practice. The descriptive analysis is analyzed first using graphs tables and charts, and then Econometric model is addressed.\n\nWe analyzed the challenges of traditional opal mining by categorizing them into four key areas: issues with opal production techniques, constraints in value enhancement, obstacles in market dynamics, and difficulties within regulatory and institutional frameworks.\n\nThe first category comprises challenges encountered at the opal mining sites, including difficulties in exploration, extraction, and proper handling techniques. In the beginning, the opal gemstone in Wollo province was discovered by farmers near Wegel Tena, specifically in the Tsehay Mewcha area (Rondeau, Mazzero, Bekele, Gauthier, & Fritsch, 2009). Subsequently, the discovery of opal resources expanded to neighboring districts, including Meket, Dawunt, Wadla, Gazo, and Angot districts. This led to the formation of numerous small mining groups that began exploring and extracting rough opal using traditional ways. Over the past seventeen years, opal exploration has continued using traditional methods, without proper training in exploration techniques or access to necessary gemstone searching equipment. The miners, all of whom are local residents, lack any geological background. They dig in various locations based on simple guesses, without understanding the geology of the area or the formations that host opal. This approach results in inefficient use of energy and significant time wastage. In addition to their traditional exploration activities, the miners rely on outdated opal extraction methods that expose them to significant risks. They dig trenches, pits, and adits to exploit opal, using homemade tools such as chisels, hammers, picks, and shovels (Fakhouri et al., 2010). Most mining tunnels are situated on the steep slopes of ridges and mountainsides, requiring extensive digging into these challenging terrains (Getaneh & Shikur, 2022). Unfortunately, this has led to numerous accidents, with many miners being buried in caves beneath sharp cliffs, resulting in loss of life. For instance, on February 8, 2024, over 20 miners were trapped in caves. Moreover, unsafe mining practices are predominant across most opal mining sites. Nearly all miners work without wearing essential safety equipment, such as helmets, goggles, masks, gloves, safety working shoes and cloth, or using proper ventilation. As a result, miners frequently suffer from injuries, severe headaches, and infectious diseases. Opal cracking is another significant issue that miners face during and after the extraction process (Tsegaye & Ayalew, 2020). This occurs primarily due to the impact of traditional mining tools on the gemstone during burrowing. Furthermore, improper handling of immature opal after mining poses additional challenges for artisanal miners. These factors contribute to an imbalance between the miners’ efforts and the benefits they receive, often leading to financial strain and crises (see Figure 2).\n\nThe second-class addresses challenges related to value addition, such as the absence of awareness creation program, lapidary training centers, and lapidary machines that could enhance the appearance of raw opal, thereby boosting its market demand and economic value. In the past, miners sold their rough opal products without adding value, and this practice continues to the present day. Our study from respondents indicates that market value of rough opal is significantly lower compared to processed or polished opal. A kilogram of raw opal costs between $720 and $1,080, with an average of $900, while processed opal can rise between $3,240 and $4,680, averaging $3,960. This reflects an increase in value by $2,520 to $3,600 after processing, or about 4 to 4.5 times the original price. Despite this substantial potential for value addition, most opal mining associations lack lapidary machines and enhancement techniques, apart from a few individuals who have received training through the MEDA project. Consequently, artisan miners typically sell their raw opal to lapidaries and smugglers instead of processing it themselves (see Figure 3).\n\nThe third group highlights market-driven issues, including pricing complexities, market access, demand fluctuations, and distribution channels that affect the profitability and viability of the opal mining industry. A significant challenge for local miner associations is the lack of market linkage with legal exporters. Nearly all associations do not have market affiliation with legitimate opal traders and instead sell their products to brokers and local lapidaries at low prices. Consequently, miners receive inadequate compensation for their products, while smugglers benefit from these opal mining activities. Another challenge faced by miners, particularly those from the Meket area who are distant from Istayish and Delanta, is the lack of access to nearby markets. Additionally, these miners are often unaware of global opal prices and thus sell their products at relatively low prices, ranging from $250 to $667 per kilogram depending on quality. In contrast, the international market values these opals between $1,000 and $1,833 per kilogram. Furthermore, those associations have no awareness about the world’s opal price; they sell their product with relatively low costs ranged from 15,000 to 40,000 ETB per kilogram of precious opals depending on the opals quality. However, in international market it proper value is extended to 60,000 to 110000 ETB. Consequently, smugglers or local lapidaries, leaving miners at a disadvantage and effectively reducing them to laborers who do not benefit fairly from their efforts, typically determine the opal’s value. A previous study at the neighboring Delanta opal mining site revealed that smugglers (illegal sellers) and exporters were the primary and secondary beneficiaries in the opal market, capturing 36% and 28% of the profits, respectively (Ayalew et al., 2020). In comparison, cutters, miners, and legal sellers accounted for only 8%, 12%, and 16% of the market profits, respectively. Similar patterns are observed at the Meket, Wadla, Angot, and Gazo opal mining sites, highlighting how the opal market system remains a critical issue in these areas. According to statistics from the focus group discussions, brokers purchase opals at very low prices without legal trade authorization. The opal miners of North wollo sold the extracted opal in local market for brokers at low cost since they have no any linkage to national and international markets. Instead of polishing and adding market value to their opal, they sold the raw opal without any quality improvement at low cost1.\n\nLastly, we assessed challenges related to regulations and institutional frameworks, encompassing the legal, policy, and organizational barriers affecting the sustainability and growth of the opal-mining sector. According to the North Wollo zone mining development office, 32 licensed opal-mining associations in the districts of Meket, Wadla, Gazo, and Angot were officially registered. However, many groups and individuals remain unlicensed, fail to follow mining office guidelines, and do not pay the required taxes. Moreover, some illegal miners have resorted to violence, using weapons to clash with licensed miners and government officials. Although some legal miners pay taxes, many do not, leading to inconsistencies between licensed and unlicensed groups. Consequently, some licensed miners may resort to illegal practices due to the lack of support from government bodies. To address these issues, universities, federal and regional mining offices, and other NGOs should focus on creating awareness, providing training, and offering support to both legal and illegal miners. In 2024, Woldia University began offering training and material support, including mining and safety tools and a few lapidary machines, to some licensed associations. However, additional efforts and support are needed to achieve effectiveness of opal miners.\n\nThe descriptive summary of both the categorical and continuous variables are analyzed using measures of mean, minimum, maximum, standard deviation, frequency, percentage, skewness and kurtosis measures as displayed in the two tables presented below.\n\nThe descriptive Summary of categorical variables (see Table 3) shows the proportion of the total sample engaged in traditional opal mining practice and their access to credit and training. Accordingly, out of the total sample of the study about 21.29% are engaging in traditional opal mining practices and sustaining their life using income obtained from the sales of opal gemstone. Out of those Artesian small-scale opal miners, 31.4% and 42.8% obtained support in the form of training and credit provision respectively. This shows that little attention is given to support small scale opal miners through proving training support relating to how to explore and extract the raw opal, how to add the value of opal applying lapidary, creating awareness about the international marker for opal mineral. That is why the opal miners in north wollo are selling one kilo gram raw opal for selling price of 40,000 to 50,000 ETB2, while one kilo gram polished opal is sold for 250,000 to 300,000 ETB in Addis Ababa which the capital city of the country. Because of this, majority of the benefit of opal mining practice is taken by the illegal agents and broker involved in the opal and other mineral market.\n\nThe above table (see Table 4), shows the summary of continues variables of the study using measures of variation and central tendency such as mean, standard deviation, skewness, and kurtosis analysis. Land size and numbers of livestock have a respective mean value of 36.13 and 8.67 from which the distribution of land size is skewed to the right while number of livestock is skewed to the left. Education level of households’ ranges from 0 to 17 3 indicating that the farmers’ education level shows high variance from illiterate farmers to fourteen years of education to mean that individuals who completed their secondary and preparatory schools are practicing traditional opal mining practices. The skewness and kurtosis values needs more explanation since those values are helpful to understand the distribution of observations to be either normal or not. A negative Skewness value indicates that variables are skewed to the left and positive values tells the present of positively skewed distribution.\n\nThe kurtosis value of for education is more than three (leptokurtic distribution) to mean that few observations lied in the middle of distribution (around the mean) and more observation has an extreme education status of very high level and low status or being illiteracy level. The remaining variables income, family size, livestock and size of arable land has a kurtosis less than three (platikurtic distribution) tell us the distribution of less of those observations lies on the outliers than the normal distribution.\n\nUnder this part of the research, variables that can affect the household’s decision to engage in traditional opal mining practice are analyzed using probit regression model. The marginal effect results of all explanatory variables are given below (see Table 5) and the effect of each variable on the probability of being participant in traditional opal mining is analyzed.\n\n* Indicates that the variable is statistically significance at 1% level of significance.\n\nAs presented in the above table ( Table 5), the marginal effect result of the probit model shows that how the explanatory variables included in the model can affect) the probability of participating in traditional opal mining practices. There for, the effect of each explanatory variables is analyzed as follows after considering their statistical significance4.\n\nThe size of arable land that the households owned has a negative impact on the probability of engaging in traditional opal mining practice. When the size of arable land owned by household farmers increased by one unit, the probability of being under the opal mining participant group decreases by 0.023. This shows that, rural households who have vast size of land are less likely involve in traditional opal mining since the agricultural income they are receiving from crop production is enough for them to sustain their life.5 Similar with this, number of livestock’s owned by rural household farmers affect the engagement status of traditional opal mining negatively; increased number of households by one unit reduces the probability of being participants of opal mining by 0.126. This shows that individual household farmers that have higher number of livestock are less likely to participate in opal mining practices. This result is supported by many researches (Chauviré et al., 2023; Getaneh & Shikur, 2022; Katona & Krapf, 2018; Legasu & Chaubey, 2023), which found inverse relationship between owning assets like land and livestock with participation in traditional mineral mining practices.\n\nThe remaining independent variables of the probit model, level of education access to training and access to credit affect the participation of opal mining positively. This result is supported by Slawson & Moffat (2020); SUORINENI (2022) and Wireko-Gyebi et al. (2023) More specifically, when level of education increases by one year, the probability of household famers to engage in traditional opal mining practice increased by 0.194. This indicates that majority of the traditional opal miners are educated individuals and hence educated individuals are more likely to be opal miners of the study area. Access to credit and access to training affect the membership of traditional opal mining group positively. The probability of individuals who accessed training have higher probability than that of their non-training accessed counter parts by 0.22. The probability of farmers who accessed credit is higher than household farmers who have not accessed it by o.33. Therefore, when households have access to credit that enabled them to purchase traditional tools used for mining and accessed training on how to extract the opal mineral using those tools easily are highly participating in the artesian small- scale opal mining activities in wollo provinces. This finding is supported by Rondeau et al. (2012); Milkias et al. (2023); Wireko-Gyebi et al. (2023) and Habte et al. (2020).\n\nIn addition to the probit model, which is used to identify the determinants of engagement status to traditional opal mining, the following table (see Table 6) presents the result of endogenous switching regression model, used to analyze the economic impact of traditional opal mining practice on rural householdsThe likelihood ratio test was significant at 5% level of significance, indicating that that the three equations, the opal mining participation equation and the outcome equations for two categories are jointly dependent. This implies that the model faced indigeneity problem and in this case; the ESR estimates are more accurate to study impact analysis than other model such as the PSM approach (Mustafa et al., 2023).\n\nIn the selection (probit model) regression, different post estimation tests have been applied to check the validity of the model. With this regard, the result of the Wald test (Watson & Teelucksingh, 2002) with p value equals with 0.0000 rejects the null hypothesis that states, “All regression coefficients are together equal to zero”. This shows that the model passes the overall significant test to indicate the presence of at least on significant variable to affect household’s engagement in opal mining.\n\nVIF for continuous for explanatory variables have applied (see Table 8) to test multi-collinearity problem and the result given by mean vif values less than 10 shows that there is no serious multi-collinearity problem among the explanatory variables. In addition to this, we applied robust regression to control the effect of heteroscedasticity problem on estimation result. The covariance between the participation equation for engagement in opal mining and the outcome equations for household income was found to be non-zero, indicating the presence of endogenous switching in the model as stated in (Bidzakin, Fialor, Awunyo-Vitor, & Yahaya, 2019) and this makes the rationality of using the ESR model.\n\nThe correlation coefficients between opal mining participation equation and the income of engagement and non-engagement are both negative (Tesfay, 2020). This negative correlation coefficients suggest that there are unobserved factors (Angrist, Imbens, & Rubin, 1996) influencing both the decision to participate in traditional opal mining practice which implies that households with higher unobserved factor (awareness) are more likely to engaged in opal mining.\n\nThe below table (see Table 7) estimates the effect of traditional opal mining on household’s income using an Endogenous Switching Regression model. The table presents the actual and counterfactual income and the average treatment effect (Dawes, 2020) on treated (ATT) and untreated (ATU), which then helped to calculate the transitional heterogeneity, which measures the difference income between the traditional opal miners in the study area (Katona & Krapf, 2018).\n\nMore specifically, the average monthly income for traditional opal miners is estimated to be 36250 ETB, but would be decreased to 4870 if they were not participating in the opal mining practice. On the other way, households who are not participating in the traditional opal mining are earning monthly income of 4625 ETB, which can be increased to 32860 ETB if they are treated and engaged in the traditional opal mining practices (George et al., 2022). Those differences are the effect traditional opal mining on the treated and non-treated groups. If the treated groups were untreated, 31380 will lower their income while the income of untreated will increased by 31625 if they were treated and engaged in the traditional opal mining practices (Herrmann & Maas, 2022). In addition to this, the results of transition heterogeneity 6 confirm that the engagement in traditional opal mining leads to higher monthly income when compared with those who are not participating in opal mining in wollo provinces. The monthly income of households who engaged in traditional opal mining practice had higher income than that of non-opal miner households by 3432 ETB. This means household farmer who engaged in opal mining would have lower benefits if they do not participate in mining, while farmers who do not engaged in opal mining will have higher benefits if they do engaged in opal mining practice. This result is consistent studies conducted by Mustoe (2023); Habte et al. (2020); Ejigu et al. (2020); DEJENE (2015) and Alemu (2018).\n\n\n5. Conclusion and recommendations\n\nThis study is conducted to investigate the challenges and economic impact of traditional opal mining in north wollo zone of Ethiopia. The study identifies three main categories of challenges faced by traditional opal miners: exploration and extraction issues, market limitations, and regulatory and institutional shortcomings. Exploration and extraction challenges include the lack of modern mining tools and knowledge, as well as difficult terrain, leading to inefficient and hazardous mining practices. Market-related challenges involve limited access to broader markets and lack of value addition, resulting in miners selling raw opals at significantly lower prices compared to polished ones. Regulatory and institutional problems exacerbate these issues, with weak enforcement and inadequate support for miners.\n\nDescriptive statistics reveal that a significant portion of the sample (21.29%) engages in traditional opal mining. However, access to training and credit is limited, contributing to low value addition and exploitation by intermediaries. The probit regression model indicates that larger land sizes and higher numbers of livestock negatively affect the likelihood of engaging in opal mining, while higher education levels, access to training, and access to credit positively influence participation.\n\nThe Endogenous Switching Regression (ESR) model shows that traditional opal mining significantly affects household income. On average, opal miners earn 36,250 ETB monthly, compared to 4,870 ETB if they did not mine. Conversely, non-miners could potentially earn 32,860 ETB if they engaged in opal mining. The transition heterogeneity analysis confirms that participation in opal mining leads to a higher income compared to non-participation, with a monthly income differential of 3,432 ETB favoring opal miners. The findings highlight the need for targeted interventions to address the challenges faced by traditional opal miners. These include improving access to modern mining tools, enhancing market linkages, and strengthening regulatory frameworks. Additionally, providing training and credit support can improve the efficiency and profitability of opal mining. Addressing these issues will not only enhance the economic benefits for miners but also contribute to sustainable development in the region. Overall, while traditional opal mining presents significant opportunities for income generation, addressing the identified challenges is crucial for maximizing its economic benefits and ensuring the well-being of mining communities in North Wollo.\n\nBased on the findings of the study, we recommend the following ideas to address these challenges and unlock the full potential of Ethiopia’s opal mining sector.\n\n➢ Training and Capacity Building: Enhancing the skills of gemstone miners and lapidaries is critical. Training programs should focus on modern mining techniques, operational health and safety, and gemstone valuation. Additionally, business training for mining cooperatives can help improve productivity and resilience.\n\n➢ Financial Support: Improving access to financing for small lapidaries and exporters is essential for enhancing competitiveness. A robust marketing strategy should be developed to communicate the unique attributes of Ethiopian opal to both domestic and international consumers. Long-term strategies could include promoting the sale of cut and polished opals directly to global markets and developing niche specializations within the sector.\n\n➢ Enhancing Cutting and Polishing Skills: Establishing partnerships between lapidary training centers and the gemstone industry can improve domestic cutting and polishing standards. Funding should be increased for training institutes to ensure sufficient practice materials and to support the development of high-quality cutters.\n\n➢ Addressing Illegal Activities: Investigating illegal gemstone supply chains and enhancing enforcement measures are crucial for protecting the legitimate market. Developing a comprehensive framework for addressing illegal activities and improving customs control can help mitigate the impact of smuggling.\n\n➢ Infrastructure and Policy Improvements: Improving infrastructure, such as roads and gemological institutes, can enhance the efficiency of gemstone trading and processing. Revising policies related to export prices and taxes could also support the growth of the domestic cutting and polishing sector.\n\nThis study, titled “Traditional Opal Mining Practice in Ethiopia, Challenges, and Its Economic Impact on Rural Households: The Case of Wollo Opal Mining,” was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The research received ethical approval from the Research and Community Service Bureau of the College of Business and Economics at Woldia University on May 10, 2024, under approval number RCSTT/184/2024. The following ethical standards were adhered to throughout the research process:\n\n1. Compliance with the Declaration of Helsinki: The study was conducted in line with the principles of the Declaration of Helsinki, which emphasizes the protection of human participants, respect for their rights and dignity, and the promotion of well-being. This research prioritized participants’ health, welfare, and confidentiality.\n\n2. Informed Consent: All participants were fully informed about the objectives, methods, risks, and potential benefits of the study. Participation was voluntary, and verbal informed consent was obtained from each participant prior to their involvement. Participants were also made aware of their right to withdraw from the study at any time without consequences.\n\n3. Confidentiality and Data Protection: Personal data was handled in strict confidence. Participant identities were anonymized, and no personally identifiable information was disclosed in the final analysis or publications. All data were securely stored, and only the research team had access to them. Data protection protocols were followed to prevent unauthorized access.\n\n4. Non-Coercion and Autonomy: No participant was coerced or pressured into participating. Autonomy was respected throughout the study, and participants were encouraged to make informed decisions regarding their participation. The research ensured that vulnerable groups, such as women or economically disadvantaged individuals, were not subjected to any form of exploitation or undue influence.\n\n5. Protection of Vulnerable Populations: The study took particular care to protect vulnerable individuals. No minors were involved in the study. “In this study, participants provided verbal consent after being fully informed about the research’s purpose, procedures, and potential risks. Verbal consent was documented as per ethical guidelines, ensuring participants understood their voluntary involvement and right to withdraw at any time. Institutional approval was obtained to use verbal consent in place of written forms.” The reason for applying this verbal consent was the presence of some illiterate respondents (local farmrers) which are involving in the this study.\n\n6. Minimizing Harm: The research team made every effort to minimize any potential risks or harms, both physical and psychological, to participants. Interview questions were designed to be non-intrusive, and participants were assured that they could skip any questions that made them uncomfortable. Should any participant experience distress, protocols were in place to provide support and discontinue the interview if necessary.\n\n7. Transparency and Feedback: Participants were informed about how the research results would be used and how they could access the findings if desired. The results will be disseminated to local communities, policymakers, and other relevant stakeholders, ensuring that the research findings contribute to improving the livelihood and economic well-being of rural households involved in traditional opal mining.\n\n\nAuthors contributions\n\n\n\n1. TWA: Generate the idea about the research title, problem statement, research objectives; write a literature review, data collection, data analysis, and recommendation.\n\n2. AZS: Literature writing, data analysis and recommendation.",
"appendix": "Data availability statement\n\nthe data used in this study is underline data fully available on respiratory called Zenodo and the DOI number for the data is stated here and on the online submission with the title traditional opal mining practice in Ethiopia, challenges and its economic impact on rural households: case of wollo opal mining obtaining license from Creative Commons Attribution 4.0 International. This data can be cited as “Abate, T. W. (2024). Traditional opal mining practice in ethiopia, challenges and its economic impact on rural households: case of wollo opal mining. Zenodo. Or can be accessed with DOI: https://zenodo.org/doi/10.5281/zenodo.13739221.\n\nThis project contains:\n\nInterview data for opal.xls\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nExtended data for this study is the interview guide line uploaded on Zenodo with title “Interview guide line for Wollo opal mining” with Doi number of https://doi.org/10.5281/zenodo.13856212. This extended data obtaining license from Creative Commons Attribution 4.0 International. It can be cited as “Tadesse Wudu, A., & Addis Zemelak, S. (2024). Interview guide line for Wollo opal mining. Zenodo. https://doi.org/10.5281/zenodo.13856212”.\n\nThis project contains:\n\ninretview guide line.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nLimitation of the study: This study is delimited to North wollo zone of Ethiopia and only one term data collected in 2023. It cannot address longitudinal data because of lack of finance and further research can be done on eastern African countries agricultural technology adoption status and its impact on welfare.\n\n\nAcknowledgment\n\nNot available\n\n\nReferences\n\nAdesugba A: Phenomenological Study of the challenges of gemstones artisanal and small-scale mining in Nigeria. California Southern University; 2018.\n\nAlemu MG: Artisanal small-scale opal mining (ASOM) insecurity in the Delanta wereda, Ethiopia: The shifting landscape of multidimensional insecurity in the face of emergent ASOM wealth. Afr. Secur. Rev. 2018; 27(1): 61–87. Publisher Full Text\n\nAlves W, Ferreira P, Araújo M: Challenges and pathways for Brazilian mining sustainability. Res. Policy. 2021; 74: 101648. Publisher Full Text\n\nAngrist JD, Imbens GW, Rubin DB: Identification of causal effects using instrumental variables. J. Am. Stat. Assoc. 1996; 91(434): 444–455. Publisher Full Text\n\nAyalew D, Pik R, Gibson S, et al.: Pedogenic origin of Mezezo opal hosted in Ethiopian Miocene rhyolites. Can. Mineral. 2020; 58(2): 231–246. Publisher Full Text\n\nBidzakin JK, Fialor SC, Awunyo-Vitor D, et al.: Impact of contract farming on rice farm performance: Endogenous switching regression. Cogent economics & finance. 2019.\n\nCartier LE: Gemstones and sustainable development: Perspectives and trends in mining, processing and trade of precious stones. Extr. Ind. Soc. 2019; 6(4): 1013–1016. Publisher Full Text\n\nChauviré B, Mollé V, Guichard F, et al.: Cracking of gem opals. Minerals. 2023; 13(3): 356. Publisher Full Text\n\nDawes JM: Synthesis, characterization, and applications of opals. Nano-Optics. Elsevier; 2020; pp. 305–325. Publisher Full Text\n\nde Brito Barreto S , Bretas Bittar SM: The gemstone deposits of Brazil: occurrences, production and economic impact. Bol. Soc. Geol. Mex. 2010; 62(1): 123–140. Publisher Full Text\n\nDejene M: THE CONTRUBUTIONS OF MAJOR MINERALS EXPORT TO THE ETHIOPIAN ECONOMY. ST. MARY’S UNIVERSITY; 2015.\n\nEgunyu F, Boakye-Danquah J: A systematic review of the socio-economic impacts of mining in Africa: Do research methods influence participation? Extr. Ind. Soc. 2024; 17: 101408. Publisher Full Text\n\nEjigu AA, Ketemu DG, Endalew SA, et al.: Challenges in Utilization of Precious Opal in Ethiopia: A Case Study from the Delanta Area, South Wollo, Ethiopia. Abyssinia Journal of Science and Technology. 2020; 5(2): 14–21.\n\nFakhouri F, Roumenina L, Provot F, et al.: Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J. Am. Soc. Nephrol. 2010; 21(5): 859–867. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeorge J, Whitten D, Metters R, et al.: Emancipatory technology and developing-world supply chains: A case study of African women gemstone miners. J. Oper. Manag. 2022; 68(6-7): 619–648. Publisher Full Text\n\nGetaneh W, Shikur M: Artisanal opal mining and associated environmental and socio-economic issues in opal mine sites of Wollo province, Ethiopia. GeoJournal. 2022; 87(4): 3323–3339. Publisher Full Text\n\nHabte AT, Mekonnen SD, Alene AN, et al.: FAAS, FT-IR and XRD Identification of Natural and Heat Treated Opals Located in Wadla Woreda, North Wello, Ethiopia.2020.\n\nHerrmann J, Maas R: Formation of Sediment-Hosted Opal-AG at Lightning Ridge (New South Wales, Australia): Refining the Deep Weathering Model. J. Geol. 2022; 130(2): 77–110. Publisher Full Text\n\nKatona L, Krapf C: Mintabie opal resource evaluation: Current value of opal resources and projected value of undiscovered resources. Department for Energy and Mining; 2018.\n\nKatona L, Krapf C: Mintabie opal resource evaluation: Current value of opal resources and projected value of undiscovered resources 2nd edition.2020.\n\nKrishnan S, Bhatia K: SOAs for scientific applications: Experiences and challenges. Futur. Gener. Comput. Syst. 2009; 25(4): 466–473. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKyngdon-McKay Y, Jorns A, Wheat B, et al.: An Analysis of the Commercial Potential of Ethiopia’s Coloured Gemstone Industry.2016.\n\nLegasu ML, Chaubey AK: Evaluation of natural radioactivity level in Delanta-Dawunt, Wollo district, Ethiopia. Int. J. Environ. Anal. Chem. 2023; 103(20): 9452–9465. Publisher Full Text\n\nMilkias M, Demissie T, Meshesha D: Geochemical insight on gem opal formation and highly weathered rhyolitic ignimbrite layer from Delanta area, south Wollo, northern Ethiopia. Arab. J. Geosci. 2023; 16(5): 335. Publisher Full Text\n\nMulaba-Bafubiandi AF, Ukponu MU, Odo AU, et al.: Contemporary Issues in the Governance and Regulation of Artisanal and Small-Scale Mining (ASM) in Africa. Mining Law and Governance in Africa. Routledge; 2023; pp. 98–129. Publisher Full Text\n\nMustafa NM, Asfaw FF, Endris EA, et al.: Evaluating the impact of productive safety net program on rural household food security achievement: Endogenous switching regression modeling approach. J. Agric. Food Res. 2023; 14: 100674. Publisher Full Text\n\nMustoe GE: Silicification of wood: An overview. Minerals. 2023; 13(2): 206. Publisher Full Text\n\nOfori R, Takyi SA, Amponsah O, et al.: Mining-induced displacement and resettlement in Ghana: an assessment of the prospects and challenges in selected mining communities. Soc. Netw. Anal. Min. 2023; 13(1): 61. Publisher Full Text\n\nOnac BP, Forti P: State of the art and challenges in cave minerals studies. Studia UBB Geologia. 2011; 56(1): 33–42. Publisher Full Text\n\nPalgutová S, Štrba Ľ: Geoheritage of the precious Opal Bearing Zone in Libanka Mining District (Slovakia) and its geotourism and geoeducation potential. Land. 2022; 11(12): 2293. Publisher Full Text\n\nQin X, Yi J, Zhang H: Quarter of Birth, Gender Inequality, and Economic Development. Gender Inequality, and Economic Development. 2024. (May 12, 2024). Publisher Full Text\n\nRondeau B, Cenki-Tok B, Fritsch E, et al.: Geochemical and petrological characterization of gem opals from Wegel Tena, Wollo, Ethiopia: opal formation in an Oligocene soil. Geochem. Explor. Environ. Anal. 2012; 12(2): 93–104. Publisher Full Text\n\nRondeau B, Mazzero F, Bekele E, et al.: New play-of-color opal from Welo, Ethiopia. Gems Gemol. 2009; 45(1).\n\nSenior BR, Deveson BJ: Queensland Precious Opal Deposits and Associated Critical Mineral Enrichment within Silicified Palaeochannels. Aust. Gemmol. 2023; 28(4).\n\nSlawson DD, Moffat AJ: How effective are citizen scientists at contributing to government tree health public engagement and surveillance needs—an analysis of the uk open air laboratories (opal) survey model. Insects. 2020; 11(9): 550. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSuryanarayana T, Seid MA: Primitive way of Opal Mining and its Impact on Environments Case study in WegelTena. Wollo, Ethiopia: 2022.\n\nSuorineni FT: Challenges and Implications for the Mining Industry for Future Resources Extraction. Int. J. Soc. Mater. Eng. Resour. 2022; 25(1): 10–17. Publisher Full Text\n\nTesfay MG: Does fertilizer adoption enhance smallholders’ commercialization? An endogenous switching regression model from northern Ethiopia. Agric. Food Secur. 2020; 9: 1–18. Publisher Full Text\n\nTrickey E, Lucifora D, Wan P, et al.: ENABLING MINE AUTOMATION THROUGH THE APPLICATION OF NEPTEC’S OPAL AND 3DRI TECHNOLOGY. Paper presented at the ISARC. Proceedings of the International Symposium on Automation and Robotics in Construction. 2013.\n\nTsegaye B, Ayalew M: Prevalence and factors associated with antenatal care utilization in Ethiopia: an evidence from demographic health survey 2016. BMC Pregnancy Childbirth. 2020; 20: 1–9. Publisher Full Text\n\nWatson PK, Teelucksingh SS: A practical introduction to econometric methods: Classical and modern. University of the West Indies Press; 2002.\n\nWireko-Gyebi R, Puwurayire P, Nyamekye K, et al.: Socio-demographic attributes of artisanal small-scale miners and their operations in Ghana. GeoJournal. 2023; 88(2): 1997–2010. Publisher Full Text\n\n\nFootnotes\n\n1 The wollo opal is the second preferred opal with high quality next to the Australian opal in the world mineral market. However, due limited attention given for the sector, the primary participants of opal mining are not benefited as their effort.\n\n2 ETB is to indicate the national currency of the country called “Ethiopian Birr”.\n\n3 Among the traditional opal miners of the study area, few respondents are BSc degree holders who had been graduated in field of Engineering. Therefore, since 5 years of higher education is required to be graduate of engineering, some respondents have a maximum year of education equal to 17 years. However, majority of the respondents are either elementary school dropouts or illiterate farmers.\n\n4 The statistical significant of variable is tested using z and p values adjacent to each variables. Using the rule of thumb, variables which have a z value higher than two of a probability value less than 5%(0.05) are statistically significant to affect the dependent variable. Following this rule, family size and marital status are statistically insignificant and hence no need of giving interpretation for the two variable. Other independent variables are tested to be statistically significant and their effect is interpreted based on their marginal effect results.\n\n5 Household who are producing higher yield of crops fears the challenges of traditional opal mining, because they are sustaining their life easily without experiencing risk of life. As explained in the challenge of opal miners in wollo provinces previously, there and many challenges to engage in the mining practice, because of this, households who are relatively under good life sustaining economic activities does not prefer to engage in opal mining practice.\n\n6 The positive significant values for the transition heterogeneity effect (TH) of income indicates that the impact of traditional opal mining on income will be significantly higher for the participants relative to the non-participant households. In reverse to this, if the TH value is negative it indicates that then treated groups are earning lower income than the counterfactuals because of participating in opal mining practices."
}
|
[
{
"id": "343281",
"date": "03 Jan 2025",
"name": "Taşkın Deniz Yıldız",
"expertise": [
"Reviewer Expertise AREA OF INTERESTS• Mining legislation• Mining exploration and operation projects• Mineral economics",
"resources economics• Costs and cost analysis",
"cost benefit analysis• Natural resources rents",
"taxation• Mining and energy/infrastructure investments conflicts• Land acquisition and land use in mining",
"land use change",
"compensation",
"evaluation of abandoned mining areas in terms of environment and urbanism",
"industrial heritage• Mining waste management",
"rehabilitation cost• Occupational health and safety in mines",
"supervising of mines."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper analyzes the problems of opal mining in Ethiopia and its impact on household incomes. There are very few studies on the effects of mining on household incomes. Therefore, this is a very valuable study that can serve as an example of practices in less developed countries. I think that if it is revised and published, it can fill an important gap in the literature. On the other hand, I think that the article should be improved in line with my suggestions below. In this direction, there are still deficiencies in the text of the article. I suggest that the article be given a \"major revision\" decision. I predict that the article will be highly cited if it is indexed after the revision.\nIn “Introduction” • “(…) Wello opal, with its exceptional play-of-color and extensive color variations, quickly gained international acclaim, leading to a notable increase in exports to major markets including India, China, Europe, and the USA (George, Whitten, Metters, & Abbey, 2022; Herrmann & Maas, 2022).” This paragraph has sentences in common with the paragraph above. Merge the two paragraphs and delete the repeated sentences.\n• “Ethiopia’s vast mineral wealth, particularly its opals, is a cornerstone of its economic potential. The country’s journey from the discovery of opals to their prominence in the international market is both intriguing and complex, reflecting the broader trends and challenges in artisanal and small-scale mining (ASM).” There are two similar sentences above. You can delete the ones above:\n• “Therefore, the objectives of this research are\nAnalyzing the challenges of traditional opal mining in Wollo provinces\n\nInvestigating the economic impact of opal mining on the household in the study area.”\nDelete these sentences as you have stated the aims of the article above and these sentences are repetitive.\nIn “Historical context of opal mining in Ethiopia” What is mentioned in this thread is an expansion of what is mentioned in the “Introduction”. To avoid repetition, those in the “Introduction” can be deleted. Or this sub-heading can be combined with similar sentences in the “Introduction”.\nIn “3.8.Ethics statement”\nAlmost the same text as in this heading appears at the end of the article, i.e. above the “References”. This heading should therefore be deleted here. However, if there is a different sentence, you can add it below. You can write “Annex 1” in front of the heading “List of declarations: Ethics and consent”.\nIn “4.1. Challenges of traditional opal mining in North wollo” • You can replace “The first category comprises challenges” with “The first category comprises technical challenges”. • You mentioned that occupational accidents are a detrimental factor to opal mining in Ethiopia. Occupational accidents increase mining costs and cause loss of profit for mining companies. (If it would disrupt the flow of this thread, it would be useful to address this issue in a “Discussion” section as factors that impair the feasibility of mining)\n• You have stated in different parts of the article that opal production cannot be made technically and economically. In the world, the feasibility of ornamental stones can be determined professionally. You can refer to the examples in Literature.\n• In Ethiopia, where small-scale mining is practiced, you mentioned the inefficiency of production in many fields. At this point, could basin mining instead of small-scale field mining contribute to making opal mining in Ethiopia more feasible? This possible higher contribution is based on the production of opal reserves identified by more technical reports of the cooperatives in Ethiopia you mentioned. You can review in Literature on this subject.\n• “15,000 to 40,000 ETB per kilogram” The article refers to both the US dollar and the “ETB”. How many ETB is one US dollar? Can you share this information by referencing it in a footnote at the appropriate place in the article where ETB is mentioned? • I suggest that you discuss the problems of mine management in a sub-heading or in an appropriate place close to the \"Discussion\" section of your article, taking into account the practices of other countries. Of course, the practices of each country are different from each other. However, the suggestions given for solving the problems in some countries may also be useful for solving the problems in Ethiopia. Because, in order to increase the incomes of households in mining areas, more feasible mining operations will be needed. Opening more or higher capacity mining operations could also increase household incomes. In this regard, you can also use the problems of mining companies in Turkey, for example, in the \"Discussion\" in the article, although some of them are not similar to the practices in Ethiopia. Turkey is an example of mining practices in other developing countries because of the problems faced by mining and the proposed solutions to these problems. Mining operations in Turkey pay many land use fees. This weakens the feasibility of mining operations. In addition, the high number of institutions and bureaucracy in obtaining mining permits can reduce the attractiveness of investments and result in the abandonment of active mining licenses. This situation directly affects the incomes of the people in the mining region. • You can benefit from the studies in Literature on the negative impact of mining permits and bureaucracy on mining investments. • You can benefit from the studies in literature on land use costs and incentivizing mining. • Do land use fees in Ethiopia negatively affect the feasibility of mining? What are the fees and types of fees charged by mining companies? Do you think these fees negatively affect households in the mining area? Or is it necessary to reduce these fees in order to increase household incomes? Or which of these royalties, and to what extent, could be beneficial to pass on to local people? You can use the studies in the literature on the share of mining royalties given to local communities in the “Discussion” of the paper. • For example, in Turkey, mining licenses can be put as capital in commercial companies. This is a factor that can increase the power of companies. Of course, there are other factors that can increase the capital power of companies. You can also develop a proposal on whether all these factors can increase the power of mine operators in Ethiopia. In particular, is there a minimum capital required by legislation for mining in Ethiopia? This minimum capital varies according to mineral groups in Turkey. • You have analyzed the impact of mining on household incomes in your article. At this point, the question arises as to how many workers are employed in each mine and how much they are paid. You have shared some numbers on this issue. On the other hand, it would be useful to make use of the studies in Literature to increase the salaries of workers or engineers working in mines.\nIn “Recommendations” The heading \"Recommendations\" is very valuable for solving the problems of opal mining in Ethiopia that you mentioned. However, these recommendations need to be filled in. In other words, is the technical, social, and economic capacity sufficient for each recommendation to be implemented in Ethiopia? In this context, a \"Discussion\" needs to be made by giving examples from other countries' practices in the literature. The \"Discussion\" should precede the \"Conclusions\" and \"Recommendations\". Subheadings can be made for the \"Discussion\" using what I have suggested above. These headings can be created not only from the existing \"Recommendations\" but also by adding factors that affect opal mining such as mining permits, land use fees, royalties, taxes, etc. that negatively affect investment attractiveness. A brief mention of these would not be a departure from the subject of the article. Making opal mining more feasible and attractive for investors will have a direct or indirect positive impact on the incomes of the people of the region.\nThe authors of the article can use all the sentences above as their own sentences (while developing their articles) in their articles. I wish you success.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "13224",
"date": "29 Jan 2025",
"name": "Tadesse Wudu Abate",
"role": "Author Response",
"response": "Dear Taşkın Deniz Yıldız, Thank you for the valuable and expertise comments you provided for this articles. we have revised the article based on you comments but failed to consider some variable yue suggested to be included because we didn't collected data on those issues. we will conduct a research in near future by adding factors that affect opal mining such as mining permits, land use fees, royalties, taxes, etc. Thank You Sir."
}
]
},
{
"id": "352841",
"date": "23 Jan 2025",
"name": "Francis F Pavloudakis",
"expertise": [
"Reviewer Expertise Mining",
"Energy",
"Mine Land Reclamation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper is very interesting as it deals with the effective exploitation of a mineral resource that is not adequately utilized to benefit mining enterprises, the local community, and the national economy of the country (Ethiopia). The structure of the paper is suitable for a scientific article, and the methodology applied has a solid scientific basis and is adequately described. However, the paper requires significant improvement in the presentation of all sections except the methodology section.\nOverall, the text needs more careful editing and improvement in the use of the English language. For example, in many instances, \"Wollo district\" is written without capitalizing the first letter. Is there a specific reason for this? Additionally, various errors such as \"the study used in this study\", \"Arstesian Opal Mining\", \"in to\", \"fifth eight\", \"household size\" instead of \"number of households\", \"kilo gram\", \"there for\", \"number of households\" instead of \"number of livestock\", \"o.33\", \"vif instead of VIF\", \"income for non-no traditional opal miners\", etc., need to be corrected. Furthermore, it would be preferable to integrate footnotes into the main text.\nIntroduction and Literature Review: It seems that the authors have directly quoted information gathered from various sources without checking if some data are repeated. These two sections need to be rewritten. In addition, the opal production data are relatively old (2010). Are there more recent data available?\nDescription of the Study Area: Although visually appealing, Figure 1 does not provide substantial information. Also, I understand that the horizontal and vertical scales are different. A simpler country map showing the position of the study area, the land morphology, and the major cities would be more informative.\nModel Specification: I do not understand why there is a reference to the Logit model since it is not used.\nEthics Statement: This section should be omitted. Any relevant reference can be included in the accompanying text.\nSection 4.1: The content of this section does not seem to result from the methodology described earlier. Either the authors should describe how they arrived at the four key challenge areas and analyzed them, OR this entire section should be moved to the literature review OR, in my opinion, to a separate fifth section entitled: Discussion.\nSection 4.2: For comparison purposes, in the last paragraph, it would be useful to provide data on the average wages in the country and the region, as well as wages by sector of economic activity. Additionally, presenting the amounts in dollars would facilitate comparisons with other countries. In the same paragraph, why are references added? Do the amounts mentioned (Table 7) not arise from the analysis conducted in the current study?\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1388
|
https://f1000research.com/articles/13-1386/v1
|
18 Nov 24
|
{
"type": "Research Article",
"title": "Bipolar Fuzzy Pseudo-UP Ideal Of Pseudo-UP Algebra",
"authors": [
"Alachew Amaneh Mechderso",
"Berhanu Assaye Alaba",
"Tilahun Mekonnen Munie",
"Teferi Getachew Alemayhu",
"Berhanu Assaye Alaba",
"Tilahun Mekonnen Munie",
"Teferi Getachew Alemayhu"
],
"abstract": "In this paper, we apply the concept of bipolar fuzzy sets to pseudo-UP ideals in pseudo-UP algebras. We prove that the intersection of two bipolar fuzzy pseudo-UP ideals is also a bipolar fuzzy pseudo-UP ideal, while the union of two such ideals does not always result in a bipolar fuzzy pseudo-UP ideal. Additionally, we discuss the concepts of bipolar fuzzy pseudo-UP ideals under homomorphism and explore several related properties. The homomorphic image and inverse image of bipolar fuzzy pseudo-UP ideals in a pseudo-UP algebra are also examined in detail. Furthermore, we study the notion of a bipolar fuzzy pseudo-UP ideal under the Cartesian product of pseudo-UP algebra. The Cartesian product of any two bipolar fuzzy pseudo-UP ideals is also the bipolar fuzzy pseudo-UP ideal of pseudo-UP algebra, and then some related results are obtained. MSC: 03G25, 06D30.",
"keywords": [
"Pseudo-UP algebra",
"pseudo-UP ideal",
"Fuzzy pseudo-UP ideal",
"bipolar Fuzzy pseudo- UP ideal"
],
"content": "Introduction\n\nIseki1 introduced BCK algebras. It is known that the class of BCK algebras is a proper subclass of the class of BCI-algebras. In 2020, Romano2 introduced the concept of pseudo-UP ideals and pseudo-UP filters and derived basic properties. In 1965, Zadeh3 popularized the concept of fuzzy sets. Since then, the concepts of fuzzy sets have been extensively used in many branches of mathematics. The fuzzifications of algebraic structures were initiated by Rosenfeld,4 and he introduced the notion of fuzzy subgroups. In 2023, Mechderso5 investigated the concept of fuzzy pseudo-UP ideals of pseudo-UP algebra. Wechler6 studied how fuzzy algebraic structures plaid vital roles in mathematics with wide applications in many other branches such as computer sciences, theoretical physics, information sciences, control engineering, topological spaces and coding theory. For a fuzzy set, its degree of membership expresses its degree of containment of elements in it. Sometimes, the degree of membership also means the degree of satisfaction of elements to some property or constraint corresponding to a fuzzy set.7 Keeping in view this notion, the membership degree 0 is in general assigned to those elements of the set that do not satisfy some property. In the usual study of fuzzy set representation, the elements with membership degree 0 are usually regarded as having the same characteristic.\n\nKeeping in view these facts, Lee8 proposed an extension of fuzzy sets named bipolar fuzzy sets. Lee9 used the notion of bipolar fuzzy set and worked on bipolar valued fuzzy subalgebras and bipolar fuzzy ideals of BCK/BCI algebra. In recent times, Alaba10 studied the notion of intuitionist fuzzy PMS ideals under homomorphism and Cartesian product and investigated several related properties.\n\nA wide variety of human decision-making is based on double-sided or bipolar judgmental thinking on a positive side and a negative side, for instance, cooperation and competition, friendship and hostility, common interests and conflict interests, effect and side effect, likelihood and unlikelihood, feed forward and feedback. The notion of bipolar fuzzy sets (YinYang bipolar fuzzy sets) was introduced by Zhang11 as a generaztion of fuzzy set.\n\nConsider a bipolar fuzzy set, as follows:\n\nFrog’s prey = {(mosquito, 1, 0), (dragon fly, 0.4, 0), (turtle, 0, 0), (snake, 0, −1)}.\n\nWe can see that membership degree 0 and non-membership degree 0 of turtle mean that frog never hunts turtle and turtle never hunts frog. While membership degree 0 and non-membership degree –1 of snake mean that frog never hunts snake but snake always hunts frog. Here, the implicit counter-property is “predator of frog,” which created the difference between fuzzy set and bipolar fuzzy set of frog’s prey.\n\nMotivated by this, we introduced the notion of a bipolar fuzzy pseudo-UP ideal of pseudo-UP algebra and proved some results. We present several results related to the bipolar fuzzy pseudo-UP ideal in pseudo-UP algebras. We investigate the properties of the homomorphic image and preimage of bipolar fuzzy pseudo-UP ideals and demonstrate that both the homomorphic image and preimage of a bipolar fuzzy pseudo-UP ideal are themselves bipolar fuzzy pseudo-UP ideals. Furthermore, the Cartesian product of bipolar fuzzy pseudo-UP ideals of pseudo-UP algebras is introduced, and several properties are investigated.\n\n\nPreliminaries\n\n\n\n[Ref. 12] A pseudo-UP algebra is algebra (X, ·, *, 0) of type (2, 2, 0) which satisfies the following axioms: for any x, y, and z ∈ X\n\n1) (y⋅z)⋅((x⋅y)∗(x⋅z))=0and(y∗z)∗((x∗y)⋅(x∗z))=0 ,\n\n2) x⋅y=0=y⋅xandx∗y=0=y∗x⇒x=y ,\n\n3) (y⋅0)∗x=xand(y∗0)⋅x=x ,\n\n4) x ≤ y if and only if x · y = 0 and x ≤ y if and only if x * y = 0.\n\n[Ref. 12] In a pseudo-UP algebra X the following holds: for any x, y ∈ X\n\n1) x≤y⋅x and\n\n2) x≤y∗x .\n\n[Ref. 2] A pseudo-UP ideal of X is a nonempty subset J of a pseudo-UP algebra X\n\nThat has the following: for each x, y, z ∈ X.\n\n1) 0∈J ,\n\n2) x⋅(y∗z)∈Jandy∈J⇒x⋅z∈J and\n\n3) x∗(y⋅z)∈Jandy∈J⇒x∗z∈J .\n\n[Ref. 2] In a pseudo-UP algebra X the following holds, for each x ∈ X,\n\n1) x · 0 = 0 and x * 0 = 0,\n\n2) 0 · x = x and 0 * x = x and\n\n3) x · x = 0 and x * x = 0.\n\n[Ref. 5] A fuzzy subset λ of a pseudo-UP algebras of X is called fuzzy pseudo-UP ideal of X if and only if it fulfill the following axioms: for any x, y, z ∈ X\n\n1) λ(0)≥λ(x) ,\n\n2) λ(x⋅y)≥min{λ(x⋅(y∗z)),λ(y)} and\n\n3) λ(x∗y)≥min{λ(x∗(y⋅z)),λ(y)} .\n\n[Ref. 8] Let X be the universe of discourse. A bipolar fuzzy set λ in X is an object having the form\n\nWhere λ−: X→ [−1, 0] and λ+: X → [0, 1] are mappings. Form this paper we use the symbol\n\nλ = (X; λ−, λ+) for the bipolar valued fuzzy set λ = {(x, λ−(x), λ+(x)): x ∈ X}, and use the notion of bipolar fuzzy sets instead of the notion of bipolar valued fuzzy sets.\n\n[Ref. 13] A bipolar fuzzy set λ = (X; λ+, λ−) in a set X with the positive membership\n\nλ+: X → [0, 1] and negative membership λ−: X → [−1, 0] is indicated to have Sup-Inf property, if for any subset T of X, there exists x0 ∈ T such that λ+(x0)=supt∈Tλ+(t) and λ−(x0)=inft∈Tλ−(t)\n\nLet λ = (X, λ+, λ−) be bipolar fuzzy set in X. Then the following statements hold for any x, y ∈ X.\n\n1) 1−max{λ+(x),λ+(y)}=min{1−λ+(x),1−λ+(y)} ,\n\n2) 1−min{λ+(x),λ+(y)}=max{1−λ+(x),1−λ+(y)} ,\n\n3) −1−max{λ−(x),λ−(y)}=min{−1−λ−(x),−1−λ−(y)} and\n\n4) −1−min{λ−(x),λ−(y)}=max{−1−λ−(x),−1−λ−(y)} .\n\n[Ref. 14] Let f: X → Y be a homomorphism from a set X onto a set Y and let λ = (X; λ−, λ+) be a bipolar fuzzy set of X and σ = (Y; σ−, σ+) be two bipolar fuzzy set of Y, then the homomorphic image f (λ) is f (λ) = (f (λ−), f (λ+)) defined as for all y ∈ Y.\n\nAnd\n\nThe pre-image f −1 (σ) of σ under f is a bipolar set defined as f −1 (σ−) (x) = σ− (f(x)) and f −1 (σ+) (x)) =σ+ (f(x)), for all x ∈ X.\n\n[Ref. 15] Let λ and σ are any two bipolar fuzz set of X and Y respectively. The Cartesian product of λ and σ is defined as λ × σ = (X × Y, λ+ × σ+, λ− × σ−) with λ+ × σ+ (x, y) = min{λ+(x),σ+(y)} and λ−×σ−(x,y)=max{λ−(x),σ−(y)} where λ+×σ+ : X×Y→[0,1] and λ−×σ− : X×Y→[−1,0] , ∀(x,y)∈X×Y .\n\n\nBipolar fuzzy pseudo-UP ideal\n\nIn this section, we introduce the concept of a bipolar fuzzy pseudo-UP ideal in pseudo-UP algebras and examine several important properties associated with bipolar fuzzy pseudo-UP ideals.\n\nA bipolar fuzzy set λ = (X, λ+, λ−) in X is called bipolar fuzzy pseudo-UP ideal of X if it satisfies the following conditions for all x, y, z ∈ X.\n\ni) λ+(0) ≥ λ+(x) and λ−(0) ≤ λ−(x),\n\nii) λ+(x · z) ≥ min {λ+(x · (y * z)), λ+(y)},\n\niii) λ+(x * z) ≥ min {λ+(x * (y · z)), λ+(y)},\n\niv) λ−(x · z) ≤ max {λ−(x · (y * z)), λ−(y)},\n\nv) λ−(x * z) ≤ max {λ−(x * (y · z)), λ−(y)}.\n\nLet X = {0, a, b, c} be a set with binary operations “·” and “*” defined by the following cayley Table 1\n\nClearly, (X, ·, *, 0) is pseudo-UP algebra. We define a bipolar fuzzy pseudo-UP ideal of X as follows.\n\nThen, λ is a bipolar fuzzy pseudo-UP ideal of X.\n\nLet λ = (X, λ+, λ−) be a bipolar fuzzy pseudo-UP ideal of a pseudo-UP algebra X with y ≤ z, for any y, z ∈ X, then λ+(y) ≥ λ+(z) and λ−(y) ≤ λ−(z), that is λ+ is order reversing and λ− is order preserving.\n\nLet λ = (X, λ+, λ−) be a bipolar fuzzy pseudo-UP ideal of pseudo-UP algebra X such that y ≤ z, for all y, z ∈ X. Then by the binary relation ≤ define in X, we have z · y = 0 and z * y = 0.\n\nHence, λ+(y) ≥ λ+ (z) and λ−(y) ≤ λ− (z). □\n\nEvery bipolar fuzzy pseudo-UP ideal λ = (X, λ+, λ−) of X is a bipolar fuzzy pseudo- UP subalgebra of X.\n\nSuppose λ is a fuzzy pseudo-UP ideal of X. Then,\n\nThus, λ = (X, λ+, λ−) is a bipolar fuzzy pseudo-UP subalgebra of pseudo-UP algebra X. □\n\nThe converse is may not be true.\n\nLet X = {0, 1, 2, and 3} be a set with a binary operations “·” and “*” defined by the following cayley Table 2.\n\nThen, (X, ·, *, 0) is a pseudo-UP algebra. We define a bipolar fuzzy set λ = (X; λ+, λ−) in X as follows:\n\nThen λ = (X; λ+, λ−) is a bipolar fuzzy pseudo-UP subalgebra of X, but it is not a bipolar fuzzy pseudo-UP ideal of X. Indeed,\n\nλ+(0 · 2) ≥ min {λ+(0 · (1 * 2)), λ+(1)} = λ+(2) ≥ min {λ+(0 · 1), λ+(1)} implies that 0.2 ≥ 0.4 which is contradict to Definition 3.1. And similarly, λ−(0 · 2) ≤ max {λ−(0 · (1 * 2)), λ−(1)} = λ−(2) ≤ max {λ−(0 · 1), λ−(1)} implies that −0.3 ≤ −0.5 which is contradict to Definition 3.1.\n\nLet λ = (X; λ+, λ−) be a bipolar fuzzy pseudo-UP ideal of a pseudo-UP algebra X. If the inequality x ≤ y · z and x ≤ y * z holds in X for all x, y, z ∈ X, the λ+(z) ≥ min {λ+(x), λ+(y)} and λ−(z) ≤ max {λ−(x), λ−(y)}.\n\nLet x, y, z ∈ X such that x ≤ y * z and x ≤ y · z. Then by the binary relation “≤” defined in X, we have x · (y * z) = 0 and x * (y · z) = 0. By Definition 3.1, we have\n\nAnd by Theorem 3.4, we have\n\nBy (3.1) and Definition 3.1\n\nBy (3.2) and (3.3), we have\n\nSimilarly,\n\nAnd by Theorem 3.4, we have\n\nBy (3.4) and Definition 3.1\n\nBy (3.5) and (3.6), we have\n\nHence, λ+(z)≥min{λ+(x),λ+(y)}andλ−(z)≤max{λ−(x),λ−(y)}. □\n\nThe intersection of any two bipolar fuzzy pseudo-UP ideals of a pseudo-UP algebra X is also a bipolar fuzzy pseudo-UP ideal.\n\nLet λ = (X; λ+, λ−) and η = (X; η+, η−) be two bipolar fuzzy pseudo-UP ideals of X. Then we claim that λ ∩ η is a bipolar fuzzy pseudo-UP ideal of X. Let x, y, z ∈ X. Then\n\nλ+∩η+(0)=min{λ+(0),η+(0)}≥min{λ+(x),η+(x)}=λ+∩η+(x).\n\nAnd λ−∩η−(0)=max{λ−(0),η−(0)}≤max{λ−(x),η−(x)}=λ−∩η−(x).\n\nHence, λ ∩ η is a bipolar fuzzy pseudo-UP ideal of X. □\n\nThe intersection of any set of bipolar fuzzy pseudo-UP ideals in a pseudo-UP algebra X is also a bipolar fuzzy pseudo-UP ideal.\n\nThe union of two bipolar fuzzy pseudo-UP ideals may not be bipolar fuzzy pseudo-UP ideal.\n\nLet X = {0, 1, 2, and 3} be a set with a binary operation “·” and “*” defined by the following cayley Table 3.\n\nClearly, (X, ·, *, 0) is a pseudo-UP algebra. We define a fuzzy set λ+: X → [0, 1] as follows, λ+(0) = 1, λ+(1) = 0.6, λ+(2) = 0.4, λ+(3) = 0.3 and we define a fuzzy set λ−: X → [−1, 0] as follows λ−(0) = −1, λ−(1) = −0.5, λ−(2) = −0.6, λ−(3) = −0.4 and a fuzzy set η+: X → [0, 1] define as follows, η+(0) = 1, η+(1) = 0.4, η+(2) = 0.5, η+(3) = 0.3. and η−: X → [−1, 0] define as follows η−(0) = −0.9, η−(1) = −0.5, η−(2) = −0.3, η−(3) = −0.2. Now, (λ+ ∪ η+)(1 · 3) = max {λ+(1 · 3), η+(1 · 3)} = max {λ+(3), η+(3)} = max{0.3, 0.3} = 0.3.\n\nHence, (λ+ ∪ η+) (1 · 3) = 0.3=.....................................(*).\n\nFrom (*) we get 0.3 ≥ 1 which is contradict to Definition 3.1.\n\nAnd (λ−∪η−)(1⋅3)=min{λ−(1⋅3),η−(1⋅3)}=min{λ−(3),η−(3)}=min{−0.4,−0.2}=−0.4(∗∗) .\n\nFrom (**), we get −0.4 ≤ −0.9 which is contradict to Definition 3.1. This shows that the union of any two bipolar fuzzy pseudo-UP ideal of X may not be a bipolar fuzzy pseudo-UP ideal of X.\n\nA bipolar fuzzy set λ = (X, λ+, λ−) in X is a bipolar fuzzy pseudo-UP ideal of X\n\nIf and only if the fuzzy subset λ+ and (λ−)c are fuzzy pseudo-UP ideals of X.\n\nLet λ = (X, λ+, λ−) be a bipolar fuzzy pseudo-UP algebra of X. We need to show that the fuzzy subset λ+ and (λ−)c are fuzzy pseudo-UP ideals of X. Clearly, λ+ is a fuzzy pseudo-UP ideal of X follows from the fact that (X, λ+, λ−) is a bipolar fuzzy pseudo-UP ideal of X. Now, it remains to show that (λ−)c is a fuzzy pseudo-UP ideal of X. Let x, y, z ∈ X, then we have (λ−)c (0) = −1 − λ− (0) ≥ −1 − λ−(x) = (λ−)c (x).\n\nHence, (λ−)c is a fuzzy pseudo-UP ideal of X.\n\nConversely, assume that λ+ and (λ−)c is fuzzy pseudo-UP ideal of X. Then for every x, y, z ∈ X, we get λ+ (0) ≥ λ+(x) and (λ−)c (0) ≥ (λ−)c(x), by Definition 3.1\n\nNow, (λ−)c (0) ≥ (λ−)c (x) implies that −1 − λ− (0) ≥ −1 − λ−(x), then λ− (0) ≤ λ−(x). Now it is suffices to show that λ−(xz) ≤ max {λ−(x·(y*z)), λ−(y)} and λ−(x*z) ≤ max {λ−(x*(y ·z)), λ−(y)}, for all x, y, z ∈ X.\n\nHence, λ = (X, λ+, λ−) is a bipolar fuzzy pseudo-UP ideal of X. □\n\nIf λ+ is a fuzzy pseudo-UP ideal of X, then λ = (X, λ+, ((λ+)c) is a bipolar fuzzy pseudo-UP ideal of X.\n\nSuppose λ+ is a fuzzy pseudo-UP ideal of X. Then we need to show that λ = (X, λ+, (λ−)c) is a bipolar fuzzy pseudo-UP ideal of X. Since λ+ is a fuzzy pseudo-UP ideal of X, it follows that λ+ (0) ≥ λ+(x), λ+(x· z) ≥ min {λ+(x· (y *z)), λ+(y)} and λ+(x*z) ≥ min {λ+(x*(y · z)), λ+(y)}, for all x, y, z ∈ X. Then it is enough to show that (λ+)c (0) ≥ (λ+)c (x), (λ+)c (x · z) ≥ min{(λ+)c (x · (y * z)), (λ+)c (y)} and (λ+)c (x * z) ≥ min{(λ+)c (x * (y · z)), (λ+)c (y)}.\n\nTherefore, λ = (X, λ+, (λ+)c) is a bipolar fuzzy pseudo-UP ideal of X. □\n\nIf (λ−)c is a fuzzy pseudo-UP ideal of X, then λ = (X, (λ−)c), λ− is a bipolar fuzzy pseudo-UP ideal of X.\n\nSimilar to Corollary 3.13.\n\nUsing those, corollary the following is obtained.\n\nA bipolar fuzzy set λ = (X, λ+, λ−) of X is a bipolar fuzzy pseudo-UP ideal of X if and only if λ = (X, λ+, (λ+)c) and ♦λ = (X, (λ−)c, λ−) are bipolar fuzzy pseudo-UP ideals of X.\n\nSuppose λ = (X, λ+, λ−) is bipolar fuzzy pseudo-UP ideal of X, then for any x, y, z ∈ X, we have λ+(0) ≥ λ+(x), λ+(x·z) ≥ min {λ+(x·(y*z)), λ+(y)} and λ+(x*z) ≥ min {λ+(x*(y·z)), λ+(y)}. Next we have to show that (λ+)c satisfies the conditions such that (λ+)c (0) ≤ (λ+)c (x), (λ+)c (x·z) ≤ max{(λ+)c (x · (y * z)), (λ+)c (y)} and (λ+)c (x * z) ≤ max{(λ+)c (x * (y · z)), (λ+)c (y)}.\n\nHence, λ is a bipolar fuzzy pseudo-UP ideal of X.\n\nAlso, for any x, y, z ∈ X, λ− (0) ≤ λ−(x), λ−(x · z) ≤ max {λ−(x · (y * z)), λ−(y)} and λ−(x * z) ≥ max {λ−(x * (y · z)), λ−(y)}. Now we have to show that (λ+) c (0) ≥ (λ+)c (x), (λ+)c (x · z) ≥ min {(λ+)c (x · (y * z)), (λ+)c (y)} and (λ+)c (x * z) ≤ min {(λ+)c (x * (y · z)), (λ+)c (y)}. So for any x, y, z ∈ X, we have (λ-)c (0) = −1 − λ−(0) ≥ −1 − λ−(x) = (λ-)c (x) ⇒ (λ−)c (0) ≥ (λ−)c (x).\n\nHence, ♦λ is a bipolar fuzzy pseudo-UP ideal of X. The proof of the converse follows from Definition 3.1.□\n\nIf λ = (X, λ+, λ−) is a bipolar fuzzy pseudo-UP ideal of X, then λc is also a bipolar fuzzy pseudo-UP ideal of X.\n\nLet λ = (X, λ+, λ−) be a bipolar fuzzy pseudo-UP ideal of X. Then λ c = (X, (λ+) c (λ−) c), where (λ+) c (x) = 1 − λ+(x) and (λ−) c (x) = −1 − λ−(x). Now, for any x, y, z ∈ X, we have (λ−) c (0) = −1−λ−(0) ≥ −1−λ−(x) = (λ−(λ−) c (x) ⇒ (λ−) c (0) ≥ (λ−) c (x) and (λ+) c 0) = 1−λ+(0) ≤ 1 − λ+(x) = (λ+) c (x) ⇒ (λ+) c (0) ≤ (λ+) c (x).\n\nTherefore, λc is a bipolar fuzzy pseudo-UP ideal of X. □\n\n\nHomomorphism on bipolar fuzzy pseudo-UP ideal\n\nIn this section, we explore bipolar fuzzy pseudo-UP ideals in the context of homomorphism. We examine the homomorphic images and inverse images of bipolar fuzzy pseudo-UP ideals in pseudo-UP algebras, and present some key findings.\n\nLet f: X→Y is an epimorphism of pseudo-UP algebras. If λ = (X, λ+, λ−) is a bipolar fuzzy pseudo-UP ideal of X with sup-inf property, then the image f (λ) is a bipolar pseudo-UP ideal of Y.\n\nAssume that λ = (X, λ+, λ−) is a bipolar fuzzy pseudo-UP ideal of X with sup-inf property. Let x, y, z ∈ Y with a ∈ f −1(x), b ∈ f −1(y) and c ∈ f −1 (z).\n\nThen by Definition 2.7, we have\n\nFinally, (f)(λ−)(x∗z)≤max{(f)(λ−)(x∗(y⋅z)),(f)(λ−)(y)}.\n\nTherefore, f (λ) is a bipolar fuzzy pseudo-UP ideal of Y. □\n\nLet f be a homomorphism on pseudo-UP algebra X onto Y and η is a bipolar fuzzy pseudo-UP ideal of Y. Then f −1 (η) is a bipolar fuzzy pseudo-UP ideal of X.\n\nLet f be a homomorphism of pseudo-UP algebra. Assume that η is a bipolar pseudo- UP ideal of Y and let x ∈ X. Then f −1(η+)(0) = η+(f(0)) ≥ η+(f(x)) = f −1(η+)(x) and f −1(η−)(0) = η−(f(0)) ≤ η−(f(x)) = f −1(η−)(x). Let x, y, z ∈ X. Then\n\nAgain, f−1(η−)(x∗z)≤max{f−1(η−(x∗(y⋅z))),f−1(η−(y))}.\n\nHence, f −1 (η) is a bipolar fuzzy pseudo-UP ideal of X.\n\nThe next theorem shows that the converse of the above Theorem 4.2 is also true if f is an epimorphism of pseudo-UP algebra. □\n\nLet f: X →Y be an epimorphism of pseudo-UP algebras. Let η be a bipolar fuzzy subset of Y. If f −1 (η) is a bipolar fuzzy pseudo-UP ideal of X, then η is a bipolar fuzzy pseudo-UP ideal of Y.\n\nAssume that f is an epimorphism of pseudo-UP algebra and f −1 (η) is a bipolar fuzzy pseudo- UP ideal of X. We need to show that η is a bipolar fuzzy pseudo-UP ideal of Y. Since f is an epimorphism of pseudo-UP algebra for any x ∈ Y, there exist a ∈ X such that f (a) = x.\n\nThen η+(0)=η+(f(0))=f−1(η+)(0))≥f−1(η+)(a)=η+(f(a))=η+(x).\n\nη−(0)=η−(f(0))=f−1(η−)(0))≤f−1(η−)(a)=η−(f(a))=η−(x).\n\nLet x, y, z ∈ Y. Then f (a) = x, f (b) = y and f(c) = z, for all a, b, c ∈ X. Thus\n\nSimilarly, η−(x⋅z)≤max{η−(x⋅(y∗z)),η−(y)} .\n\nTherefore, η is a bipolar fuzzy pseudo-UP ideal of Y. □\n\n\nCartesian products of bipolar fuzzy pseudo-UP ideal\n\nIn this section, we discuss the Cartesian product of two bipolar fuzzy pseudo-UP ideal is also again a bipolar fuzzy pseudo-UP ideal and some other results are also investigated.\n\nLet λ = (X, λ+, λ−) and σ = (Y, σ+, σ−) be any two bipolar fuzzy pseudo-UP ideals of X and Y respectively. Then λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y.\n\nAssume that λ and σ be any two bipolar fuzzy pseudo-UP ideals of X and Y respectively.\n\nTake (x, y) ∈ X × Y. Then\n\nLet (x1, x2), (y1, y2), (z1, z2) ∈ X × Y. Put x = (x1, x2), y = (y1, y2), z = (z1, z2). Then,\n\nAnd, λ+×σ+(x∗z)≥min{λ+×σ+(x⋅(y∗z)),λ+×σ+(y)} .\n\nAnd,\n\nAdditionally, λ−×σ−(x∗z)≤max{λ−×σ−(x⋅(y∗z)),λ−×σ−(y)}.\n\nHence, λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. □\n\nLet λ and σ be two bipolar fuzzy subsets of X and Y. If λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. Then the followings are true.\n\n1) λ+(0) ≥ σ+(y) and σ+(0) ≥ λ+(x),\n\n2) λ− (0) ≤ σ−(y) and σ− (0) ≤ λ−(x).\n\n1) Assume σ+(y) ≥ λ+ (0) and λ+(x) ≥ σ+ (0), ∀x ∈ X, y ∈ Y\n\n\n\n2) Similarly, λ−(x)≤σ−(0)andσ−(y)≤λ−(y),∀x∈X,y∈Y\n\nThus proving the result. □\n\nIf λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y for any two bipolar fuzzy subsets λ and σ of X and Y respectively, then either λ is a bipolar fuzzy pseudo-UP ideal of X or σ is a bipolar fuzzy pseudo-UP ideal of Y.\n\nLet λ and σ be any two bipolar fuzzy subsets of pseudo-UP algebra X and Y respectively such that λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. Then λ+ × σ+ (0, 0) ≥ λ+ × σ+(x, y). Now by Lemma 5.2, let λ+ (0) ≥ λ+(x) or σ+ (0) ≥ σ+(y) and λ− (0) ≤ λ−(x) or σ− (0) ≤ σ−(y).\n\nLet (x1, x2), (y1, y2), (z1, z2) ∈ X × Y. Put x = (x1, x2), y = (y1, y2), z = (z1, z2).\n\n\n\n⇒ either λ+(x1 · z1) ≥ min {λ+(x1 · (y1 *z1)), λ+ (y1)} or σ+(x2 · z2) ≥ min {σ+(x2 · (y2 *z2)), σ+ (y2)}. And either λ+(x1*z1) ≥ min {λ+(x1*(y1·z1)), λ+ (y1)} or σ+(x2*z2) ≥ min {σ+(x2*(y2·z2)), σ+ (y2)}. Similarly we can show that either λ−(x1 · z1) ≤ max {λ−(x1 · (y1 * z1)), λ−(y1)} or σ−(x2 · z2) ≤ max {σ−(x2 · (y2 * z2)), σ−(y2)} and λ−(x1 * z1) ≤ max {λ−(x1 * (y1 · z1)), λ−(y1)} or σ−(x2 * z2) ≤ max {σ−(x2 * (y2 · z2)), σ−(y2)}. Hence, either λ is a bipolar fuzzy pseudo-UP ideal of X or σ is a bipolar fuzzy pseudo-UP ideal of Y. □\n\nLet λ and σ be any bipolar fuzzy subsets of X and Y respectively. Then λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y if and only If λ+ × σ+ and (λ− × σ−)care fuzzy pseudo-UP ideals of X × Y.\n\nLet λ and σ be any two bipolar fuzzy subsets of X and Y respectively such that λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. Now we need to show that λ+ × σ+ and (λ− × σ−)c are fuzzy pseudo-UP ideals of X × Y. Clearly, λ+ × σ+ is a fuzzy pseudo-UP ideal of X × Y. So it remains to show that (λ− × σ−)c is a fuzzy pseudo-UP ideal of X × Y.\n\nNow, for every (x1, x2), (y1, y2), (z1, z2) ∈ X × Y.\n\nHence, (λ− × σ−)c is a fuzzy pseudo-UP ideal of X × Y.\n\nConversely, assume that λ+ × σ+ and (λ− × σ−)c are fuzzy pseudo-UP ideals of X × Y. We need to show that λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. Let (x1, x2), (y1, y2), (z1, z2) ∈ X × Y. Then λ+×σ+(0,0)≥λ+×σ+(x1,x2)andλ−×σ−(0,0)≤λ−×σ−(x1,x2) .\n\nNow, we have (λ−×σ−)c(0,0)≥(λ−×σ−)c(x1,x2)⇒−1−λ−×σ−(0,0)≥−1−λ−×σ−(x1,x2)⇒(λ−×σ−)(0,0)≤(λ−×σ−)(x1,x2)\n\nλ+×σ+((x1,x2)⋅(z1,z2))≥min{λ+×σ+((x1,x2)⋅((y1,y2)∗(z1,z2))),λ+×σ+(y1,y2)}.\n\nAnd, λ+×σ+((x1,x2)∗(z1,z2))≥min{λ+×σ+((x1,x2)∗((y1,y2)⋅(z1,z2))),λ+×σ+(y1,y2)} .\n\nSimilarly, λ−×σ−((x1,x2)∗(z1,z2))≤max{λ−×σ−((x1,x2)∗((y1,y2)⋅(z1,z2))),λ−×σ−(y1,y2)} .\n\nHence, λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. □\n\nLet λ and σ be any two bipolar fuzzy subsets of X and Y, respectively. Then λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y if and only if □ (λ × σ) = (X × Y, λ+ × σ+, (λ+ × σ+)c) and ♦ (λ × σ) = (X × Y, (λ− × σ−)c, (λ− × σ−) are bipolar fuzzy pseudo-UP ideals of X × Y.\n\nAssume that λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. Now we need to show that (λ×σ) and ♦ (λ×σ) are bipolar fuzzy pseudo-UP ideal of X×Y. Then for any (x1, x2), (y1, y2), (z1, z2) ∈ X ×Y, we have λ+ ×σ+(0, 0) ≥ λ+ ×σ+(x1, x2), λ+ ×σ+((x1, x2) · ((z1, z2)) ≥ min {λ+ ×σ+((x1, x2) · ((y1, y2)*(z1, z2))), λ+×σ+(y1, y2)} and λ+×σ+((x1, x2)*((z1, z2)) ≥ min {λ+×σ+((x1, x2)*((y1, y2)· (z1, z2))), λ+ × σ+(y1, y2)}.\n\nNext, let (x1, x2), (y1, y2), (z1, z2) ∈ X × Y. we have (λ+ × σ+)c (0, 0) = 1 − λ+ × σ+ (0, 0) ≤1 − λ+ × σ+(x1, x2) = (λ+ × σ+)c (x1, x2).\n\nHence, (λ × σ) is a bipolar fuzzy pseudo-UP ideal of X × Y.\n\nAnd, (λ−×σ−)c(0,0)=−1−λ−×σ−(0,0)≥−1−λ−×σ−(x1,x2)=(λ−×σ−)c(x1,x2) .\n\nHence, ♦ (λ × σ) is a bipolar fuzzy pseudo-UP ideal of X × Y.\n\nConversely, assume that γ(λ × σ) and ♦ (λ × σ) are bipolar fuzzy pseudo-UP ideals of X × Y. It is clear that λ × σ is a bipolar fuzzy pseudo-UP ideal of X × Y. □\n\n\nConclusion\n\nIn this paper, we discussed the bipolar fuzzy pseudo-UP ideal of a pseudo-UP algebra and investigated several related properties. We proved that the intersection of two bipolar fuzzy pseudo-UP ideals is bipolar fuzzy pseudo-UP ideal. The union of two bipolar fuzzy pseudo-UP ideals is not always a bipolar fuzzy pseudo-UP ideal. We studied the homomorphic image and the inverse image of the bipolar fuzzy pseudo-UP ideal of pseudo-UP algebra and obtained some interesting results. We proved the Cartesian product of any two bipolar fuzzy pseudo-UP ideals in pseudo-UP algebra and investigated related results. We hope that the findings of this study will add new dimensions to the structures of bipolar fuzzy pseudo-UP ideals based on bipolar fuzzy sets and will serve as a foundation for further study into the structures of fuzzy pseudo-UP ideals by using the concept of bipolar fuzzy subset of pseudo-UP algebra.\n\n\nAuthor contributions\n\nAll the authors are contributed equally in this manuscript and also both authors read and approved the final manuscript.\n\n\nEthics and consent\n\nEthics and consent were not required.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nIséki K: On axiom systems of propositional calculi. XV. Proc. Jpn. Acad. 1966; 42(3): 217–220. Publisher Full Text\n\nRomano DA: Pseudo-UP ideals and pseudo-UP filters in pseudo- UP algebras. Math. Sci. Appl. E-Notes. 2020; 8(1): 155–158. Publisher Full Text\n\nZadeh LA: Fuzzy sets. Inf. Control. 1965; 8(3): 338–353. Publisher Full Text\n\nRosenfeld A: Fuzzy groups. J. Math. Anal. Appl. 1971; 35(3): 512–517. Publisher Full Text\n\nMechdesro AA, Alaba BA, Munie TM, et al.: Fuzzy pseudo-UP ideal of pseudo-UP algebra. Res. Math. 2023; 10(1): 2234217. Publisher Full Text\n\nWechler W: The concept of fuzziness in automata and language theory.1978. (No Title).\n\nZimmermann HJ: Fuzzy set theory and its applications. Springer Science & Business Media; 2011.\n\nLee KM: Bipolar-valued fuzzy sets and their operations. Proc. Int. Conf. on Intelligent Technologies. Bangkok, Thailan: 2000; pp. 307–312.\n\nLee KJ: Bipolar fuzzy subalgebras and bipolar fuzzy ideals of BCK/BCI-algebras. Bull. Malaysian Math. Sci. Soc. 2009; 32(3): 361–373.\n\nAlaba BA, Derseh BL, Wondifraw YG: On Intuitionistic Fuzzy PMS-Ideals of a PMS-Algebra under Homomorphism and Cartesian product. Int. J. Comput. Intell. Syst. 2023; 16(1): 68. Publisher Full Text\n\nZhang WR: Bipolar fuzzy sets and relations. A computational framework for cognitive modeling and multiagent decision analysis. NAFIPS/IFIS/NASA’94. Proceedings of the First International Joint Conference of the North American Fuzzy Information Processing Society Biannual Conference. The Industrial Fuzzy Control and Intelligent. 1994; pp. 305–309.\n\nRomano DA: Pseudo-UP algebras. An introduction. Bull. Int. Math. Virtual Inst. 2020; 10(2): 349–355.\n\nLele C, Wu C, Weke P, et al.: Fuzzy ideals and weak ideals in BCK-algebras.2001.\n\nJun YB: Fuzzy d-ideals of d-algebras. J. Fuzzy Math. 2000; 8(1): 123–130.\n\nSabarinathan S, Kumar DC, Muralikrishna P: Bipolar valued fuzzy α-ideal of BF-algebra. Circuits and Systems. 2016; 07(10): 3054–3062. Publisher Full Text"
}
|
[
{
"id": "344899",
"date": "18 Dec 2024",
"name": "Baravan Asaad",
"expertise": [
"Reviewer Expertise Topology",
"Fuzzy Set Theory",
"Soft Set Theory",
"Decision Making."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript presented a new concept of pseudo-UP algebras called bipolar fuzzy pseudo-UP ideal which is combine between bipolar fuzzy sets and pseudo-UP ideal. Some theoretical results are presented via this new concept of pseudo-UP algebras.\nI have only the following points: - What is the comparison between the existing concept and the previous concept?\nTherefore, I recommend to accept this manuscript for indexing.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "344905",
"date": "24 Dec 2024",
"name": "Ubaid Ur Rehman",
"expertise": [
"Reviewer Expertise fuzzy algebra",
"decision making",
"algebraic structures"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI have read the manuscript thoroughly and decided that the idea is new but the paper in recent shape cannot be accepted. I am adding some specific comments below. So, my decision regarding the current version of the manuscript is a major revision. Comments:\nThe abstract should be improved. The present abstract is not up to the mark.\n\nThe motivation of the proposed theory need a lot of improvement. The authors must discuss that what is the requirement of this theory to be developed. The authors interpreted the concept of bipolar valued algebraic structure, so they must discuss some recent work on fuzzy groups such as Bipolar Complex Fuzzy Subgroups [ref 1], Bipolar Complex Fuzzy Semigroups [ref 2], Analysis of Γ-Semigroups Based on Bipolar Complex Fuzzy Sets [ref 3] , T-Bipolar Soft Groups and Their Fundamental Laws [ref 4], Bipolar complex fuzzy submodules [ref 5] in the introduction.\n\nThere must be suitable punctuation mark after every equation. The theoretical work is okay but what is the application of the proposed work? The authors must add an application of the bipolar valued fuzzy groups to show the practicality of their work. Improve the language of the whole manuscript with the help of native English speakers, and the structure of each section to ensure the readability of the manuscript. The conclusion is written like a contribution, but there is no deep analysis of obtained knowledge, no discussion, or wider application. How the authors can expand their work to other mathematical frameworks such bipolar complex fuzzy set devised by Tahir Mahmood? The author should discuss it in the future direction by citing 2 to 3 articles of bipolar complex fuzzy set for better future work. Add some merit and limitations of the proposed work.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "344908",
"date": "26 Dec 2024",
"name": "M Balamurugan",
"expertise": [
"Reviewer Expertise Fuzzy Algebra"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is quite interesting to review this article entitled “Bipolar Fuzzy Pseudo-UP Ideal Of Pseudo-UP Algebra” In this paper, we apply the concept of bipolar fuzzy sets to pseudo-UP ideals in pseudo-UP algebras. We prove that the intersection of two bipolar fuzzy pseudo-UP ideals is also a bipolar fuzzy pseudo-UP ideal, while the union of two such ideals does not always result in a bipolar fuzzy pseudo-UP ideal. Additionally, we discuss the concepts of bipolar fuzzy pseudo-UP ideals under homomorphism and explore several related properties. The homomorphic image and inverse image of bipolar fuzzy pseudo-UP ideals in a pseudo-UP algebra are also examined in detail. Furthermore, we study the notion of a bipolar fuzzy pseudo-UP ideal under the Cartesian product of pseudo-UP algebra. The Cartesian product of any two bipolar fuzzy pseudo-UP ideals is also the bipolar fuzzy pseudo-UP ideal of pseudo-UP algebra, and then some related results are obtained. However, the paper has been minor revisions in present form but need the following corrections:\nIn page 8, 0.3= ………………(*), remove = In page 9, theorem 3.12 and corollary 3.14, (l-)c instead of (l-)c and l = (X, (l-)c, l-) instead of l = (X, (l-)c), l- In page 9, corollary 313, l = (X, l+, (l+)c) instead of l = (X, l+, ((l+)c). Throughout the paper check it. In page 14, proof of the condition 2) σ-(y) ≤ l-(0) instead of σ-(y) ≤ l-(y). In references, the recent references to add in the related work. [Ref 1[ and [Ref 2].\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1386
|
https://f1000research.com/articles/13-918/v1
|
12 Aug 24
|
{
"type": "Research Article",
"title": "Laboratory findings predictive of critical illness in hospitalized COVID-19 patients in Tunisia",
"authors": [
"Donia Belkhir",
"Hana Blibech",
"Line Kaabi",
"Saoussen Miladi",
"Mohamed Aymen Jebali",
"Jalloul Daghfous",
"Nadia Mehiri",
"Ahmed Laatar",
"Nozha Ben Salah",
"Houda Snene",
"Bechir Louzir",
"Hana Blibech",
"Line Kaabi",
"Saoussen Miladi",
"Mohamed Aymen Jebali",
"Jalloul Daghfous",
"Nadia Mehiri",
"Ahmed Laatar",
"Nozha Ben Salah",
"Houda Snene",
"Bechir Louzir"
],
"abstract": "Background COVID-19 disease has spread rapidly worldwide, causing high mortality. Accessible biomarkers capable of early identification of patients at risk of severe form are needed in clinical practice. The aim of the study was to determine the biological markers that predict a critical condition.\n\nMethods Retrospective study including patients with confirmed COVID-19 hospitalized between September 2020 and June 2021. The primary endpoint was progression to critical status within 7 days from admission. We defined two groups: Critical group: Patients who developed a critical condition or died or transferred to the ICU before or at 7th day. Non-critical group: Patients who remained in non-critical respiratory status until 7th day or discharged before or at 7th day.\n\nResults Our study included 456 patients, with a sex ratio of 1.32 and an average age of 62 years. At the 7th day of hospitalization, 115 (25.2%) patients were in the critical group and 341 (74.8%) patients were in the non-critical group. The univariate logistic regression indicated that laboratory findings between non-critical and critical groups showed that C-reactive protein (CRP) (p=0.047), D-Dimer (p=0.011), creatinine (0.026), creatine kinase (p=0.039), lactate dehydrogenase (p=0.04), and troponin (p=0.001) were all higher among patients in critical group. However, lymphocyte (p<0.001) and platelet (p<0.001) counts were significantly lower among the critical group. Multivariate logistic regression model, identified four independent risk factors: lymphopenia (OR=2.771, 95%CI=1.482-5.181, p=0.001), Neutrophil to Lymphocyte Ratio (OR=2.286, 95%CI=1.461-3.578, p<0.001), thrombocytopenia (OR=1.944, 95%CI=1.092-3.459, p=0.024), and CRP>71.5 (OR=1.598, 95% CI=1.042-2.45, p=0.032) were associated to critical group.\n\nConclusions Our results show the predictive value of some biological markers to evaluate the prognosis of COVID-19 pneumonia. A prognostic score could be proposed for guiding clinical care and improving patient outcomes.",
"keywords": [
"COVID-19",
"Viral pneumonia",
"Critical illness",
"Adult respiratory distress syndrome",
"Biomarkers",
"Prognosis"
],
"content": "Introduction\n\nIn December 2019, a novel coronavirus caused viral pneumonia cases in Wuhan, China, spreading globally. Termed SARS-CoV-2, it was declared a “public health emergency of international concern” in January 2020, impacting various levels. Tunisia reported imported COVID-19 cases in March 2020, with a milder initial wave due to strict measures. The second wave strained care facilities in July 2020 due to eased preventive measures.1 Tunisia’s limited healthcare resources posed challenges, necessitating hospital reorganization and resource optimization. Intensive care units expanded, and departments like pulmonology were dedicated to COVID-19 care. Identifying high-risk patients and predictors of severe outcomes has become of paramount importance. Severe SARS-CoV-2 cases exhibited vascular processes caused by inflammation, leading to complications such as acute respiratory distress syndrome (ARDS) and cardiovascular issues.2,3 Urgent identification of predictors guided risk assessment and intervention studies. This contributed to the effective allocation of resources and informed clinical decision-making. Moreover, distinguishing severe cases using parameters like haematological and inflammatory markers improved clinical management.4,5 This is a study performed at University Hospital Center Mongi Slim, focused on COVID-19 patients hospitalized between October 2020 and June 2021 in the COVID-19 unit comprising Pulmonology and Rheumatology departments. The objectives of this study was to describe the clinical and evolutionary characteristics of hospitalized patients with COVID-19 and to determine predictive biological markers of a critical condition on the 7th day of admission.\n\n\nMethods\n\nThis was a retrospective study, conducted at University Hospital Center Mongi Slim, including patients hospitalized for COVID-19 pneumonia between October 2020 and June 2021 in the COVID-19 unit: Pulmonology Department and Rheumatology Department, which were jointly managed in collaboration between the two teams.\n\nInclusion and exclusion criteria:\n\nEligible patients were those admitted to the COVID-19 unit between October 2020 and June 2021 with moderate to severe COVID-19 pneumonia at admission, confirmed for SARS-CoV-2 via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Rapid Antigen Test (RAT), or positive SARS-CoV-2 serology (IgM or IgG) for vaccine-naive patients.\n\nPatients were not included if they had a mild COVID-19 infection throughout their hospitalization and another reason for hospitalization, if they were patients admitted to the COVID-19 unit after an initial stay in the intensive care unit, or if they remained in the emergency department for more than 7 days before being admitted to the COVID-19 unit.\n\nWe excluded patients who were admitted to the COVID-19 unit with hypoxemic pneumonia and suggestive findings of COVID-19 pneumonia on thoracic CT scan but with negative virological results (RT-PCR, RAT, and SARS-CoV-2 serologies), and an alternative cause was identified during the course of the disease. Additionally, patients were excluded if virological documentation data could not be located.\n\nOutcome measure:\n\nWe defined the development of a critical state before or on the 7th day of hospitalization (D7) as the outcome measure. Patients were categorized into two groups:\n\n1) Critical Group: Event group including:\n\n• Patients who developed a critical state by D7. The definition of a critical state will be detailed in the following paragraph.\n\n• Patients who died before or on D7.\n\n• Patients transferred to the intensive care unit before or on D7.\n\n2) Non-Critical Group: Non-event group including:\n\n• Patients who maintained a stable and non-critical respiratory state until D7.\n\n• Patients discharged from the hospital before or on D7.\n\n• Patients transferred to the intensive care unit before or on D7.\n\nDefinition of a Critical State: We defined a critical state as:\n\n• The occurrence of Acute Respiratory Distress Syndrome (ARDS) requiring invasive or non-invasive respiratory support. For this criterion, we defined the oxygen requirement level of 10 liters with a high-concentration mask as the threshold for evolving into ARDS.\n\n• Vital distress or shock, sepsis, and/or organ failure. In all cases, intensive care unit admission is indicated. We relied on the definitions from the World Health Organization (WHO) version of November 20216 and the National Evaluation and Accreditation Agency for Health (INEAS) version of April 20217 to establish the definition of a critical state.\n\nDefinition of ARDS: We defined the oxygen requirement level of 10 liters with a high-concentration mask as the threshold for evolving into ARDS. This threshold was considered throughout the COVID unit’s activity based on the medical team’s experience as an indicator of a critical state and warranting alerting the intensive care units.\n\nData were retrospectively and anonymously collected between June 2023 and January 2024. All demographic, clinical, biological, radiological, therapeutic, and progression-related data were extracted from the medical records. The medical records followed a standardized format with predefined items consistently used in both departments of COVID-19 unit. The collected information included demographic data, clinical details recorded at admission and D7, and biological data obtained at admission. For the latter, all patients underwent a routine standard biological assessment at admission complete blood count (CBC) including leukocytes, lymphocytes, neutrophils, platelets, hemostasis profile (Prothrombin Time, Activated Partial Thromboplastin Time, D-Dimers), renal profile (Urea, Creatinine, Blood Ionogram), liver profile (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT)), markers of muscle injury (Creatine Kinase (CK), Lactate Dehydrogenase (LDH)), and C-Reactive Protein (CRP). Some parameters were unavailable due to reagent shortages, and others were optional based on clinical presentation, such as Troponin and N-terminal prohormone of brain natriuretic peptide (NT-ProBNP). Chest computed tomography (CT) data were recorded at admission and upon aggravation during evolution. Therapeutic data included oxygen therapy, antibiotic treatment, corticosteroids, anticoagulation, and other measures, adhering to a uniform protocol guided by INEAS recommendations. Evolvement data covered hospital discharge, transfers to intensive care, COVID-19 unit deaths, and complication occurrences.\n\nFor the analysis of the association between two qualitative variables, we used Pearson’s Chi-squared test to compare two frequencies when the conditions for its application were met, and the Fisher’s test otherwise. For the analysis of the association between a qualitative variable and a quantitative variable, we employed the Student’s t-test to compare two means in the case of a normal distribution, and the non-parametric Mann Whitney test otherwise. Correlations between two quantitative variables were calculated using the Pearson correlation coefficient, with significance tested bilaterally. In the multivariate study, a binary logistic regression model was followed, and the risk was computed as the Odds Ratio (OR) with a retained 95% confidence interval (CI 95%). To assess performance, we utilized parameters related to the Receiver Operating Characteristic (ROC) Curve, as well as sensitivity and specificity. Pre- and post-test probabilities were determined through likelihood ratios represented on the Fagan nomogram. We set the significance threshold at p ≤ 5%.\n\nThis retrospective study received approval from the Ethics Committee of University Hospital Center Mongi Slim, under approval number 57/2023 on Friday, 22 December 2023.\n\nWe followed strict ethical committee guidelines that allowed for exemption of consent, due to the non-intrusive nature of the study and the use of non-identified data to ensure confidentiality and anonymity of participants. All personally identifiable data were anonymized prior to analysis to protect individuals’ privacy. We also carefully assessed the risks and benefits of our research, ensuring to minimize the former and maximize the latter for participants and the scientific community. No financial or other conflicts of interest were identified by the authors of this study. Policies regarding the future use of data and their potential sharing with other researchers were strictly established in accordance with ethical guidelines.\n\n\nResults\n\nAmong 626 patients hospitalized in the COVID-19 unit of University Hospital Center Mongi Slim for a period of 9 months (October 2020 - June 2021), we selected 456 patients after applying the inclusion and exclusion criteria. The number of included, not included, and excluded patients is summarized in the flowchart below (Figure 1).\n\n1) Patient characteristics\n\nOn the 7th day of hospitalization, 115 (25.2%) evolved to a critical condition. Among the patients in the study, 260 (57%) were males; 196 (43%) were females. The gender of the patients was not statistically significant between critical and non-critical groups (p=0.106). As shown in Table 1, Chi-square outcome indicated that the age differed significantly between the critical and non-critical patients (p=0.004). In fact, the mean age for the non-critically ill patients was 61.5 ± 13.2 years while the critically ill patients had a mean age of 65.7 ± 14. Chronic concomitant diseases were found among 322 patients (70.6%), with no significant difference between both groups. The mean time from onset of symptoms to admission into the COVID-19 unit was 8.5 ± 4.12 days. This lapse was significantly shorter for the critically ill patients: 7.9 vs 8.8 days (p=0.022). Among the total cases, 31.4% had an extent of lesions greater than 50% on chest CT, the critical group had a higher proportion of cases with an extent exceeding 50% (37% versus 25.6%, p=0.021).\n\n2) Laboratory test outcomes\n\nThe CBC findings shown in Table 2 indicate that concentration of the lymphocytes were statistically lower among critically ill patients (0.85 ± 0.24) compared to non-critically ill patients (1.10 ± 0.33, p<0.001). Lymphopenia also occurred among 89.5% of patients in critical group (p=0.002) (Table 3). Similarly, the platelet count was lower among the critical group (203 vs 235, p<0.001). The level of WBC and neutrophil did not statistically differ between both groups.\n\nThe mean Neutrophil-to-Lymphocyte ratio (NLR) was 7.52. The NLR at admission was higher in the critical group with a marginally significant difference (p=0.073). There was also a significant correlation between the NLR and the extent of lesions on the chest CT (r=0.213, p<10−3).\n\nThe CRP concentration outcome is the other biochemistry test that was statistically significantly different between critically ill (122 ± 78) and non-critically ill patients (106 ± 72, p=0.047). Upon admission, data regarding levels of D-dimer (full data available for 136 patients), hypersensitive troponin (full data available for 117 patients), B-type natriuretic peptide (full data available for 67 patients) were obtained. As shown in Table 2, in comparison to the non-critically ill patients, patients with critical illness had significantly higher levels of D-Dimer, hypersensitive and NT-pro-BNP. Besides, patients with severe pneumonia had higher rates of rhabdomyolysis markers than patients exhibiting less critical forms of the disease; (CK: 127 vs 83, p=0.039), (LDH: 831 vs 701, p=0.04). However, the findings presented in Table 2 indicate that the concentration of AST and ALT did not vary between both groups.\n\nThe univariate logistic regression indicated that laboratory findings between non-critical and critical groups showed numerous differences including C-reactive protein (p=0.047), D-Dimer (p=0.011) and creatinine (0.026) as well as, creatine kinase (p=0.039), lactate dehydrogenase (p=0.04), troponin (p=0.001) and NT-pro-BNP level (p=0.011) which were all higher among patients in critical condition. On the other hand, lymphocyte (p<0.001) and platelet (p<0.001) counts, natremia (p=0.011) and kalemia (p=0.029) were significantly lower among the critical group, whereas liver enzymes showed no significant differences. Table 3 summarizes the biological abnormalities on admission.\n\nBased on the multivariate logistic regression model, four variables were demonstrated as independent risk factors. As shown in Table 4, the results indicated that lymphopenia (OR=2.771, 95%CI=1.482-5.181, p=0.001), NLR (OR=2.286, 95%CI=1.461-3.578, p<0.001), thrombocytopenia (OR=1.944, 95%CI=1.092-3.459, p=0.024), and CRP>71.5 (OR=1.598, 95% CI=1.042-2.45, p=0.032) were associated with critical outcome.\n\nThe threshold values of 71.5mg/L for the CRP level and 5 for the RNL were defined according to the study of the ROC curve according to the critical and non-critical groups. The findings in Table 4 show that statistically significant AUCs were obtained for CRP (AUC=0.533, p=0.032) and NLR (AUC=0.589, P<0.001). Thus, the performance of the NLR was slightly superior to that of the CRP in predicting a critical condition on day 7 (Figure 2). For a threshold equal to 71.5 mg/L, the sensitivity and specificity of CRP to predict critical illness were respectively equal to 66.1% and 38.1%, while for a threshold equal to 5, the sensitivity and specificity of the NLR to predict the critical illness were respectively equal to 68.7% and 51% (Table 5). Figure 2 and Figure 3 show the area under the ROC curve of CRP and NLR (Figure 2) and platelet count (Figure 3). The platelet count was negatively correlated with the occurrence of a critical condition and it was quite efficient in predicting non-critical cases; (AUC=0.62; CI95%=0.56-0.679) (Figure 2). The best threshold was estimated at 187.5*103 elements/mm3 corresponds to a sensitivity and specificity equal to 72.4% and 48.7% respectively with a quite good accuracy (Table 6).\n\n\nDiscussion\n\nBased on the univariate analysis of our study, some biomarkers were predictive of the progression to a critical state on the 7th day of hospitalization for COVID-19 pneumonia.\n\nA significant difference in biochemical and CBC test parameters was found between critically and non-critically ill patients, with elevated CRP, D-dimer, creatinine, CK, LDH, troponin and NT-Pro-BNP among the critical group compared to the non-critical group. Added to that, lymphocytes and platelet count were higher among the non-critical group. Our findings showed that the parameters with good specificity and sensitivity in predicting a critical outcome among COVID-19 patients are: CRP>71.5 mg/L and NLR>5.\n\nAnalysis of demographic characteristics revealed that critically ill patients were older than non-critically-ill ones which aligns with previous studies’ results.8 However, this age difference was smaller compared to that reported previously, noted as 20 years.9\n\nWe underline the fact that the study sample of COVID-19 patients cared during the study involved more males than females, as well among both groups (critical and non-critical), which supports previous observations that indicate gender as a potential determinant of likelihood to develop serious complications and unfavorable outcome. In fact, a multicenter study conducted in China, including 1099 patients hospitalized for COVID-19 pneumonia in 552 hospitals,10 had shown a clear male predominance (58%). This male susceptibility has been clearly elucidated in an Italian study,11 in which, two significant factors incriminated in the initiation of viral infection were emphasized, namely angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), both of which are influenced by gender.\n\nMoreover, this observed difference could also be attributed to behavioral differences between the sexes, notably that smoking and alcohol consumption are more often seen among men12 heightening the risk of chronic comorbidities such as cardiovascular and chronic pulmonary diseases, which have been associated with a greater likelihood of developing severe illness with COVID-19.13\n\nOur univariate analysis findings regarding the CBC parameters were different to previous findings.14,15 Previous studies concluded that increased neutrophils count is characteristic of patients with severe cases.16 Evidence suggests that severe COVID-19 is associated with elevated neutrophil levels, which increase inflammation via cytokine storm, and hemorrhages especially in the lungs, which occur as a result of neutrophil-induced tissue damage.\n\nAccording to our data, lymphopenia occurred in 78% of cases. The lymphocyte count ranged between 500 and 1000/mm3 among 36.6% of our patients while 8.8% had deep lymphopenia (< 500/mm3). Furthermore, in the critical group of patients, lymphopenia was more common (89%). Our results also showed, using the multivariate logistic regression model, that lymphopenia was an independent risk factor for a severe illness. These findings are in line with the literature. Indeed, several studies have assessed the impact of lymphopenia on disease severity. For example, Zhang and al.17 reported an average blood lymphocyte count of 1200/mm3, and Jiang and al.9 showed that 41% of patients had a lymphocyte count of less than 1000/mm3. This count was significantly lower in patients with an unfavorable outcome. Additionally, Bellan and al.18 demonstrated that a low lymphocyte count at admission was correlated with the risk of mortality due to SARS-CoV-2 infection. Two Chinese meta-analyses19,20 have concluded that patients with severe COVID-19 pneumonia had lower blood lymphocyte counts compared to non-severe forms, and lymphopenia was associated with a three-fold higher risk of severe infection, particularly ARDS. They, therefore, suggest that lymphocyte count and lymphopenia could be an effective indicator for quickly identifying patients at risk of severe pneumonia. Indeed, lymphocytes play a fundamental role in maintaining adaptive immune responses against viral infections. When viral particles resulting from the replication of SARS-CoV-2 spread through the respiratory mucosa, it leads to a cytokine storm, generating a cascade of immune responses primarily involving CD4 and CD8 T lymphocytes.21 Four main mechanisms have been recognized as responsible for lymphopenia22: Sequestration of lymphocytes in target organs and their direct infection by the virus, as these cells express the ACE2 receptor; Damage of lymphatic organs such as the thymus and spleen by the virus; Apoptosis of lymphocytes due to the increase of pro-inflammatory cytokines (TNF-α, IL-6, etc.) and Inhibition of lymphocytes by substances produced during certain metabolic disorders.\n\nIn our study, thrombocytopenia was present among 13% of cases and was correlated with the progression to a critical condition (p=0.023). We demonstrated that thrombocytopenia was associated with an odds ratio (OR) of 1.94 of developing a critical condition. Our findings are consistent with those of the literature. Indeed, a meta-analysis of 21 studies including 3,377 SARS-CoV-2 positive patients4 found that platelet count was negatively correlated with the severity of the infection as well as mortality. Another meta-analysis involving 1,779 COVID-19 patients23 revealed that thrombocytopenia was associated with a threefold higher risk of severe disease, and mortality. Moreover, the platelet count was also correlated with disease severity scores and the risk of mortality in intensive care units.24,25 Platelet count was considered as an independent risk factor for COVID-19 mortality. This count was significantly lower in COVID-19 patients who died compared to survivors.18,26 Platelet kinetics could also help to identify patients at risk of an unfavourable outcome.27 In COVID-19 patients, thrombocytopenia appears to be multifactorial. In the case of ARDS, there is a significant platelet consumption resulting from the combination of viral infection and mechanical ventilation, leading to endothelial damage and platelet activation, aggregation, and thrombus formation in the lungs.23,27 Moreover, the lung can be a site for platelet release from mature megakaryocytes, and alteration of the pulmonary capillary bed can affect platelet degranulation and pulmonary megakaryocytopoiesis.23,27\n\nIn our study, the mean NLR was 7.52. This ratio was higher in the critical group patients (p=0.073). As we previously mentioned, lymphopenia was more common among patients in a critical condition. It appears logical to observe a trend of increasing NLR in severe forms. This finding was consistent with studies of both Yang and al.28 and Yan and al.,29 where a higher NLR was correlated with severe forms and mortality, respectively (p<10−3). NLR is a biomarker that integrates two subtypes of leukocytes representing two inversely related immune pathways. It provides information about systemic inflammation and is a useful biomarker for predicting bacterial infection, including pneumonia, better than absolute leukocyte, lymphocyte, or neutrophil counts.29 A high NLR reflects a discrepancy in the inflammatory response.29 Numerous studies and meta-analyses30–32 have proved that an increased NLR is associated with a poor prognosis in various diseases, such as cardiovascular diseases, solid cancers, and infections.\n\nIncreased NLR during COVID-19 could be a result of the expression of inflammatory cytokines, an unusual increase in pathological low-density neutrophils, and the upregulation of genes involved in the lymphocyte cell death pathway caused by SARS-CoV-2 infection.33 Furthermore, two studies34,35 have proposed integrating the NLR into nomograms to prove the prognostic value of this biomarker. In these studies, the authors demonstrated that NLR values at admission were higher in severe or critical cases34 and that patients with an NLR greater than 4.87 were 8 times more likely to develop a severe or critical form of the disease.35 The NLR threshold varies according to studies. An NLR threshold >3.7 on Day 7 was a major predictor of progression to severe illness, while an NLR>11.75 was significantly correlated with in-hospital mortality from all causes.29\n\nOur study showed that for a threshold ≥ 5, the sensitivity and specificity of NLR in predicting critical status on Day 7 were 68.7% and 51%, respectively. This sensitivity was 56.52% in the study by Liu and al.35 Moreover, we further demonstrated that patients with an increased NLR (>5) were as much as 2.286 times (95% CI: 1.461-3.578) more likely to develop the severe/critical type than those with a low NLR (≤5). Therefore, NLR is an objective, simple, and inexpensive parameter that could be used in routine practice as a prognostic biomarker.\n\nThrombotic complications and coagulopathy represent a major event during SARS-CoV-2 infection. An increase in D-dimer and fibrinogen levels and a decrease in prothrombin time indicate a state of hypercoagulability. Many studies have shown that high levels of D-dimer are associated with severe36,37 and critical8 forms, the need for intensive care management,2,15 and in-hospital mortality due to COVID-19 pneumonia.26,38 This hypercoagulability in COVID-19 patients could result from several mechanisms39: in viral infections, there is often an unbalance between pro-inflammatory response and anti-inflammatory response; this can lead to endothelial cell dysfunction and excessive thrombin production; hypoxia contributes to thrombosis by increasing blood viscosity. In addition to that, hospitalized patients, typically have risk factors for hypercoagulability due to age, comorbidities, extended hospital stay, and invasive treatments.\n\nIncreased D-dimer levels indicate that the fibrinolytic system is activated in COVID-19 patients. Furthermore, the increased release of cytokines during viral infections stimulates coagulation cascade.40 Moreover, D-dimer >2.0 mg/L at admission were an independent predictor of death, and dynamic changes in serum D-dimers were closely associated with disease severity. A reduction in D-dimer levels was observed in recovered patients, independently of anticoagulant treatment, while a continuous increase in D-dimer levels was predictive of a higher risk of thrombosis and unfavorable outcomes.39,41 Thus, D-dimers are an early and reliable marker for predicting a poor prognosis in COVID-19 hospitalized patients.39\n\nIn our study, thromboembolic events occurred among 11 patients. The incidence of pulmonary embolism (PE) in COVID-19 patients is still unknown and likely underestimated.42 Bilaloglu and al. reported a prevalence of PE of 3.2% in a study involving 3,334 COVID-19 patients in New York,43 while according to a French study,44 the incidence of PE was 23.7%. This difference could be explained by differences in disease severity, patient characteristics, and the limited use of CT angiography among patients.\n\nBiochemical tests findings, showed that the critical group of patients had elevated level of CRP, D-Dimer, creatinine, lactate dehydrogenase, creatine kinase, troponin and NT-Pro-BNP, which corroborates the conclusion made by Feng and al.37\n\nThe CRP was elevated (>8 mg/L) in 93.5% of patients with an average of 110 ± 73 mg/L. We noted that the CRP on admission was significantly higher in the critical group (p=0.047). In multivariate analysis, an elevated CRP level was correlated with an increased risk of progressing to a critical condition on the 7th day of admission (OR: 1.598; 95% CI: 1.042-2.45; p=0.032), and for a threshold of 71.5 mg/L, the sensitivity and specificity of CRP in predicting a critical condition were 66.1% and 38.1% respectively. Many studies have shown that elevated CRP levels are correlated with critical forms,8,36 disease progression,45 and mortality from COVID-19 pneumonia.18 As known, CRP is a non-specific marker of inflammation induced by interleukin-6 secretion. In clinical practice, it is used as a biomarker for various inflammatory and infectious conditions. High CRP levels have been directly correlated with the inflammation’s degree and disease severity.46 Moreover, CRP levels among dead COVID-19 patients were decuple higher than survivors.47\n\nA meta-analysis of 20 studies including 4,843 COVID-19 patients and focusing on the clinical utility of CRP,48 emphasized that high CRP level was associated with a fourfold higher risk of an unfavorable outcome (p<10−3). In fact, at the early stages of COVID-19 infection, an increase in CRP was directly associated with the development of lung lesions, reflecting the severity of the disease.48,49 Furthermore, Ali and al.50 demonstrated that CRP level could predict disease worsening among non-severe cases, indicating 5% risk of progressing to a severe form for each unit increase in the CRP rate. Added to that, the CRP level has also been reported as a reliable biomarker for treatment responses in COVID-19 patients16; in fact, this marker could be used to select patients who would benefit from treatment with tocilizumab, another IL-6 receptor inhibitor similar to sarilumab.51,52\n\nOur findings indicated that NLR and CRP are good predictors of unfavorable outcome. The reported excellent accuracy of these parameters in the prediction of COVID-19 patients’ outcome corroborates findings of the studies of Yang and al.28 and. Liu and al.35\n\nWe found that blood creatinine (p=0.026) and urea levels (p=0.061) were higher in the critical group. Furthermore, urea levels were significantly higher in elderly patients (> 70 years old) (p<10−3) and in patients with high blood pressure (p=0.012). Elevated blood urea (≥ 7 mmol/L) was noted in 46.6%. These findings align with the literature, where it has been demonstrated that elevated blood creatinine and urea values are associated with severe disease, unfavorable prognosis, and significant mortality.38,53,54 The mechanism of renal involvement in COVID-19 is likely to be multifactorial.53 It involves direct cytopathic effects on kidney tissue by the virus leading to renal cell necrosis as well as indirect damage by cytokines and metabolites induced by hypoxia, shock, or rhabdomyolysis.\n\nIncreased liver enzymes level was found in 39.5%, especially in male patients (p<10−3), while AST and ALT rates did not vary between both groups. Numerous studies have demonstrated the association between high transaminase levels and the severity of the disease,36,37,54,55 transfer to the intensive care unit2,15,56,57 and death26,38 due to COVID-19. Moreover, the good accuracy of AST and ALT as a predictor of ICU admission have been clearly shown with AUC>0.7.58 Added to that, Malik and al. demonstrated in their meta-analysis48 that high levels of AST and ALT (> 40 IU/L) were associated with a threefold higher risk of a poor prognosis. Some studies have shown that COVID-19 only transiently increases transaminases. Cytolysis is rather due to liver damage secondary to systemic inflammatory processes or to the use of hepatotoxic drugs, especially antivirals such as Lopinavir and Ritonavir during patient management.48,59 However, viral RNA has been detected in the liver at high titers, exceeding viremia, during autopsies, suggesting that SARS-CoV-2 hepatic infection can contribute to elevation of transaminase levels in patients with severe forms of COVID-19.41,60 In addition, hypoxia observed in COVID-19 patients induces hepatocellular necrosis through the production of free radicals that increase the release of hepatotoxic pro-inflammatory factors.48\n\nRegarding rhabdomyolysis markers, we found an elevation of LDH and CK levels among 98% and 24% of our patients, respectively. We also demonstrated that muscle lysis enzymes were significantly higher in critical group patients. Our data were consistent with the literature, where it has been shown that high levels of LDH and CK were associated with the severity5,61 and progression62 of the disease, transfer to intensive care units, and mortality54 from COVID-19. In a meta-analysis assessing the prognostic value of LDH levels,38 it was found that elevated LDH levels were associated with a risk of mortality (OR: 16) and severe disease (OR: 6). Furthermore, a study conducted on COVID-19 patients63 showed that increased LDH levels at the early stage of the disease can predict lung damage and severe cases of COVID-19. These high LDH levels may result from decreased tissue oxygenation leading to stimulation of the glycolytic pathway or from damage of multiple organs in case of multi-organ failure.48 Additionally, severe infections can induce cytokine-mediated tissue damage and LDH release. Since LDH is present in alveoli, it is common to observe elevated LDH levels in patients with severe forms of COVID-19.64 Moreover, CK is a marker of muscle injury. Thus, an acute elevation of CK indicates rhabdomyolysis. The mechanism of viral myositis is unclear, but some authors suggest that myocyte damage is immune-mediated through the deposition of immune complexes in muscles.48 Therefore, LDH and CK levels are considered as important biomarkers in the prognosis of patients with severe and critical COVID-19.41\n\nConcerning cardiac injury markers, we found that elevated levels of cardiac troponins were correlated with critical conditions (p=0.001). Indeed, troponins have a prognostic value in sepsis65 and have been proposed as severity markers15 of the disease and predictors of COVID-19 mortality.26,38 These disturbances in cardiac enzymes can result from viral myocarditis, which is more frequent during the cytokine storm, myocardial damage caused by cytokines or microangiopathies and coronary spasms secondary to hypoxia.66\n\nFurthermore, according to our data, we observed an increase in NT-Pro-BNP levels among 25 patients (5.5%), indicating a left heart failure. Additionally, the mean NT-Pro-BNP value was higher in the critical group of patients (p=0.011). NT-Pro-BNP is a hormone secreted by the left ventricular cardiomyocytes in response to increased stretching of myocardial fibers. This biomarker helps diagnose and estimate the severity of heart failure. The mechanisms of heart failure can be attributed to an imbalance between increased cardiac output and reduced oxygen supply, with the possibility for type 2 myocardial infarction.67 According to Li and al.,36 NT-Pro-BNP>500pg/L were significantly associated with severe forms of COVID-19, and Hong and al.,8 demonstrated that critically ill patients had higher NT-Pro-BNP levels (p=0.002). Therefore, cardiac biomarkers, including troponins and NT-Pro-BNP, can reflect cardiovascular involvement in COVID-19, since they are independent risk factors for poor prognosis and mortality.67,68\n\nOur study has shown that some biochemical and CBC tests are important in predicting COVID-19 patients’ need for ICU care. Specifically, laboratory tests that should be prioritized to determine patient risk of developing severe COVID-19 pneumonia, include lymphopenia, NLR, thrombocytopenia, CRP, D-Dimer, creatinine, LDH, CK, troponin and NT-Pro-BNP. NLR is most preferred as it was noted to be a very good test.\n\nHowever, limitations should be considered in the interpretation of our findings. First, our study is retrospective and monocentric. Second, some biological parameters were missing in the medical records and other specialized tests are not commonly performed in our hospital such as Interleukine-6 and Procalcitonin given their cost. Also, the lack of systematic data on blood gas analysis on Day 7, did not allow us to evaluate PaO2/FiO2 ratio, to define ARDS. Besides, the study did not consider the influence of pre-existing health conditions. Despite its limitations, this study has provided insights into laboratory parameters that can be used to predict the severity of COVID-19 cases allowing prediction of severe illness at the time of admission.\n\nIt is therefore recommended that healthcare providers consider these parameters in making evidence-based decisions regarding patient management especially where there are limited ICU facilities.\n\n\nConclusion\n\nIn conclusion, we have identified certain biological markers that can be used to assess the risk of COVID-19 pneumonia progressing to a critical state. In patients hospitalized with moderate to severe forms, we recommend close monitoring of leukocyte count, lymphocyte count, platelet count and CRP.\n\nSince the beginning of the pandemic, it has been scientifically important to analyze the discriminatory capacity of hematological, biochemical, inflammatory and immunological biomarkers in patients with COVID-19, with or without a severe or critical form. Determining risk categories after the diagnosis of COVID-19 is essential for better resource allocation, improved clinical management and prevention of serious complications.\n\nThis retrospective study received approval from the Ethics Committee of University Hospital Center Mongi Slim, under approval number 57/2023 on Friday, 22 December 2023.\n\nWe followed strict ethical committee guidelines that allowed for exemption of consent (institute policy), due to the non-intrusive nature of the study and the use of non-identified data to ensure confidentiality and anonymity of participants. All personally identifiable data were anonymized prior to analysis to protect individuals’ privacy. We also carefully assessed the risks and benefits of our research, ensuring to minimize the former and maximize the latter for participants and the scientific community Policies regarding the future use of data and their potential sharing with other researchers were strictly established in accordance with ethical guidelines.",
"appendix": "Data availability\n\nThe data supporting the findings of this study are not publicly available due to ethical concerns. However, fully de-identified data will be made available upon request from reviewers and readers. Interested parties should contact the corresponding author at donia.belkhir@fmt.utm.tn to request access to the data. Data requests will be reviewed in accordance with the local ethical committee.\n\n\nReferences\n\nChouikha A, Fares W, Laamari A, et al.: Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19. Viruses. 2022 Mar 17; 14(3): 624. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang C, Wang Y, Li X, et al.: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 [cited 2022 Dec 17]; 395(10223): 497–506. 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PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nAli N: Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID-19. J. Med. Virol. 2020 Nov [cited 2023 Mar 23]; 92(11): 2409–2411. PubMed Abstract | Publisher Full Text Reference Source\n\nPonti G, Maccaferri M, Ruini C, et al.: Biomarkers associated with COVID-19 disease progression. Crit. Rev. Clin. Lab. Sci. 2020 Sep; 57(6): 389–399. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang C, Wu Z, Li JW, et al.: Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int. J. Antimicrob. Agents. 2020 May [cited 2023 Mar 23]; 55(5): 105954. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCheng Y, Luo R, Wang K, et al.: Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May; 97(5): 829–838. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHu L, Chen S, Fu Y, et al.: Risk Factors Associated With Clinical Outcomes in 323 Coronavirus Disease 2019 (COVID-19) Hospitalized Patients in Wuhan, China. Clin. Infect. Dis. 2020 Nov 19 [cited 2023 Jan 8]; 71(16): 2089–2098. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang D, Li R, Wang J, et al.: Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect. Dis. 2020 Jul 16; 20(1): 519. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGopaul CD, Ventour D, Thomas D: Laboratory predictors for COVID-19 Intensive Care Unit admissions in Trinidad and Tobago. Dialogues Health. 2022 Dec [cited 2023 Mar 8]; 1: 100022. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang G, Zhang J, Wang B, et al.: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. Respir. Res. 2020 [cited 2023 Mar 8]; 21: 74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMardani R, Ahmadi Vasmehjani A, Zali F, et al.: Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study. Arch. Acad. Emerg. Med. 2020 Apr 4 [cited 2023 Oct 28]; 8(1): e43. Reference Source\n\nCai Q, Huang D, Yu H, et al.: COVID-19: Abnormal liver function tests. J. Hepatol. 2020 Sep; 73(3): 566–574. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFan Z, Chen L, Li J, et al.: Clinical Features of COVID-19-Related Liver Functional Abnormality. Clin. Gastroenterol. Hepatol. 2020 Jun 1 [cited 2023 Mar 29]; 18(7): 1561–1566. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nZhang G, Hu C, Luo L, et al.: Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. J. Clin. Virol. 2020 Jun; 127: 104364. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJi D, Zhang D, Xu J, et al.: Prediction for Progression Risk in Patients With COVID-19 Pneumonia: The CALL Score. Clin. Infect. Dis. 2020 Sep 15 [cited 2023 Jan 8]; 71(6): 1393–1399. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang J, Meng G, Li W, et al.: Relationship of chest CT score with clinical characteristics of 108 patients hospitalized with COVID-19 in Wuhan, China. Respir. Res. 2020 [cited 2023 Oct 28]; 21: 180. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHan Y, Zhang H, Mu S, et al.: Lactate dehydrogenase, an independent risk factor of severe COVID-19 patients: a retrospective and observational study. Aging (Albany NY). 2020 Jun 24 [cited 2023 Mar 31]; 12(12): 11245–11258. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBessière F, Khenifer S, Dubourg J, et al.: Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med. 2013 Jul 1 [cited 2023 Apr 1]; 39(7): 1181–1189. PubMed Abstract | Publisher Full Text\n\nTersalvi G, Vicenzi M, Calabretta D, et al.: Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J. Card. Fail. 2020 Jun; 26(6): 470–475. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBattaglini D, Lopes-Pacheco M, Castro-Faria-Neto HC, et al.: Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19. Front. Immunol. 2022 Apr 27 [cited 2023 Mar 30]; 13: 857573. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen T, Wu D, Chen H, et al.: Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26 [cited 2023 Jan 13]; 368: m1091. Publisher Full Text Reference Source"
}
|
[
{
"id": "319441",
"date": "04 Sep 2024",
"name": "Stelvio Tonello",
"expertise": [
"Reviewer Expertise Pharmacology internal medicin Virology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper presented by Belkir and colleagues offers a glimpse into the possibility of identifying new parameters and new biomarkers for COVID-19 patients with severe syndrome. The study was carried out by analyzing patients who had contracted the infection during the first wave of covid-19\nthe work presents excellent insights for analysis. 1) the inclusion and exclusion parameters are defined but it is not clear whether the patients analyzed were at their first infection or not\n2) when the data are analyzed and discussed, no reference is made to the studies carried out in previous years\n3 The insufficiency of some data, although justified, makes the paper lacking in information that could be very interesting In conclusion, despite having some limitations and missing a paragraph on the status of the studies carried out over the same period (this paragraph is required), publication is recommended\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12785",
"date": "18 Nov 2024",
"name": "Donia Belkhir",
"role": "Author Response",
"response": "We would like to thank you for reviewing our article, and for your valuable comments, which have contributed to improving the quality of our manuscript. We have addressed each of your suggestions and comments in detail, as outlined below: 1) The inclusion and exclusion parameters are defined but it is not clear whether the patients analyzed were at their first infection or not: -All patients were at their first infection. We added this information in the methods section 2) When the data are analyzed and discussed, no reference is made to the studies carried out in previous years: -Some of our results are consistent with studies of MERS and SARS, and we have reported certain findings in these two diseases. *In conclusion, despite having some limitations and missing a paragraph on the status of the studies carried out over the same period (this paragraph is required): -We appreciate your suggestion. As per your recommendation, we have added the results of two Tunisian studies conducted during the same period as ours. We have also added a paragraph explaining the variability between studies in terms of periods, waves and variants. We believe that this does not affect the relevance of our results, regardless of the period and the variant. ."
}
]
},
{
"id": "314706",
"date": "12 Nov 2024",
"name": "Vignesh Mariappan",
"expertise": [
"Reviewer Expertise Biomarker Identification",
"Virology",
"and Vaccines"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this manuscript, Belkhir and the team aimed to identify potential prognostic biomarkers for predicting severe disease outcomes in COVID-19 patients. The study compared two groups -critical and non-critical patients who were infected during the first wave of SARS-CoV-2 virus. Their data suggest differences in the levels of certain clinical biological indicators and their association with the critical group. Overall, the study is well-designed and employs robust statistical analysis. Overall Comments Since 2020, numerous research studies and reports have been indexed regarding potential biomarkers for the early prediction of COVID-19 disease outcomes.\nGiven the emergence of several variants of SARS-CoV-2, do the authors believe their findings could be applicable for evaluating the prognosis of COVID-19 patients infected with different variants?\nComments: Introduction\nThe introduction does not clarify the relationship between study markers and SARS-CoV-2 infection.\nMethodology\nWhy was the 7th day of hospitalization chosen as an outcome measure? Are patients transferred to the intensive care unit before or on Day 7 classified as critical or non-critical? This classification is repeated for both outcome measure, which is bit confusing. If a patient from the non-critical group progresses to a critical state is that patients included in the critical group. The definition of ARDS could be removed for brevity. Please condense the study section into 2-3 paragraphs. More details about D-dimer, CRP, Troponin and NT-Pro-BNP measurement should be further explained has a separate section each?\nResults\nWhat clinical symptom is used to calculate the time of onset of symptoms to admission in the COVID-19 unit? In Table 1, the authors indica that 11 patients from the non-critical group were transferred to the ICU. Based on the study’s critical group outcome measure, were these 11 patients included in the critical group? In Table 3, please remove the word “elevated” from the side headings. Does “N” in the side heading of Table 3 refers to mean or count?\nDiscussion and limitation\nThe discussion and limitation section is lengthy and may lose the reader’s interest. Consider streamlining this section to enhance engagement.\nConclusion\nThe authors provided a generalized statement in the conclusion/ Please specify the major findings concisely. Please modify the same in abstract section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12824",
"date": "18 Nov 2024",
"name": "Donia Belkhir",
"role": "Author Response",
"response": "We would like to thank you for reviewing our article, and for your valuable comments, which have contributed to improving the quality of our manuscript. We have addressed each of your suggestions and comments in detail, as outlined below: Overall comments: 1- Given the emergence of several variants of SARS-CoV-2, do the authors believe their findings could be applicable for evaluating the prognosis of COVID-19 patients infected with different variants? Response: Yes, We have added in the limitations section that we took into consideration the fact that our study included several variants of the virus, which impacts the clinical presentation and the outcome of the infection. However, we believe that although the period of our study is lagged compared to the studies cited in the discussion, our results remain relevant for assessing the prognosis of patients with COVID-19, regardless of the variant. Introduction: 1) The introduction does not clarify the relationship between study markers and SARS-CoV-2 infection: Response:We added a paragraph in the introduction section, clarifying the relationship between SARS-COV2 infection and the study of biomarkers. Methodology: * Why was the 7th day of hospitalization chosen as an outcome measure? Response: Several studies have shown the variation over time of the various markers, accompanying the “cytokine storm” that precedes the onset of ARDS, which usually occurs after 8 to 12 days from the onset of symptoms. Hence, we chose the 7th day after hospitalization, approximately corresponding to the 14th day after symptom onset, as the threshold for classifying patients into critical or non-critical groups. We added a paragraph explaining the phenomenon of cytokine storm and our choice of the 7th day of hospitalization. *Are patients transferred to the intensive care unit before or on Day 7 classified as critical or non-critical? This classification is repeated for both outcome measure, which is bit confusing. Response: Patients transferred to the intensive care unit before or on day 7 were classified as critical. (It was incorrect to mention this phrase in the \"non-critical\" paragraph, we corrected it). *If a patient from the non-critical group progresses to a critical state is that patients included in the critical group: Response: Patients who developed critical state after day 7 were not considered among the critical group. * The definition of ARDS could be removed for brevity Response: This section was removed. *Please condense the study section into 2-3 paragraphs Response: This section was condensed in 3 paragraphs. *More details about D-dimer, CRP, Troponin and NT-Pro-BNP measurement should be further explained as a separate section each Response: We added a short description to detail each marker Results: * What clinical symptom is used to calculate the time of onset of symptoms to admission in the COVID-19 unit? Response: Any of the 6 symptoms listed in Table 1 * In Table 1, the authors indicate that 11 patients from the non-critical group were transferred to the ICU. Based on the study’s critical group outcome measure, were these 11 patients included in the critical group? Response: Patients transferred to ICU after day 7 were not considered as critical. * In Table 3, please remove the word “elevated” from the side headings. Response: The word “Elevated” was replaced by “Increased” (Please note that the items in this table correspond to marker abnormalities, and the number of patients with abnormalities, and not to their levels). * Does “N” in the side heading of Table 3 refers to mean or count? Response: N refers to the count. Discussion and limitation 1. The discussion and limitation section is lengthy and may lose the reader’s interest. Consider streamlining this section to enhance engagement. Response: We have removed some parts that do not affect the scope of the discussion. Conclusion 1. The authors provided a generalized statement in the conclusion/ Please specify the major findings concisely. Please modify the same in abstract section Response:Some specifications related to the majors findings were added in this section as well as in the abstract"
}
]
}
] | 1
|
https://f1000research.com/articles/13-918
|
https://f1000research.com/articles/13-496/v1
|
17 May 24
|
{
"type": "Systematic Review",
"title": "A Scoping Review of Existing Policy Instruments to Tackle Overweight and Obesity in India: Recommendations for a Social and Behaviour Change Communication Strategy",
"authors": [
"Nishibha Thapliyal",
"Shalini Bassi",
"Deepika Bahl",
"Kavita Chauhan",
"Kathryn Backholer",
"Neena Bhatia",
"Suparna Ghosh-Jerath",
"Lopamudra Tripathy",
"Preetu Mishra",
"Seema Chandra",
"Monika Arora",
"Nishibha Thapliyal",
"Deepika Bahl",
"Kavita Chauhan",
"Kathryn Backholer",
"Neena Bhatia",
"Suparna Ghosh-Jerath",
"Lopamudra Tripathy",
"Preetu Mishra",
"Seema Chandra",
"Monika Arora"
],
"abstract": "Background The Indian government is committed to address various manifestations of malnutrition, including overweight and obesity, inorder to improve individual health and well-being. The scoping review aims to map existing national policy instruments (programmes, schemes, regulations and guidelines) addressing overweight and obesity in India and analysing them for Social and Behaviour Change Communication (SBCC) strategies.\n\nMethods Systematic identification and selection of policy instruments using ‘Arksey and O’Malley’ framework was conducted from central government ministry websites, between March and June 2023. These instruments focused on nutrition and/or physical activity, targeting specific demographic groups like pregnant women, lactating mothers, children (0-5 years and 5-9 years), or adolescents (10-19 years); excluding those focusing on specific diseases like micronutrient deficiencies, wasting, and stunting. Based on search strategy six policy instruments were included and analysed for SBCC strategies.\n\nResults While many policy instruments incorporated SBCC plans; the ‘National Programme for Prevention of Non-Communicable Diseases (NP-NCD)’ stands out as a significant policy initiative specifically targeting the prevention of overweight and obesity within the broader context of Non-Communicable Diseases. It adopts a comprehensive approach addressing key drivers contributing to overweight/obesity across multiple levels of behavioural influence i.e., individual, interpersonal, community and organisation for health promotion. However, there’s need to strengthen SBCC strategies related to prevention and management of obesity, especially screening and counselling, to cover all age groups with a particular focus on adolescents and youth. SBCC strategies can also be incorporated into India’s Integrated Nutrition Support Programme (POSHAN 2.0) and/or Reproductive, Maternal, New-born, Child, Adolescent Health and Nutrition (RMNCAH+N) under the National Health Mission.\n\nConclusion This paper underscores the necessity for comprehensive strategies to address multifaceted origin of overweight and obesity. The NP-NCD stands out as a noteworthy initiative, and there is considerable potential for other programmes to emulate it SBCC strategies to bolster their overall effectiveness.\n\nNote : *Policy instrument’s throughout the paper has been used to cover programmes, schemes, regulations and guidelines.",
"keywords": [
"Obesity",
"overweight",
"children",
"adolescents",
"pregnant women",
"lactating women",
"overnutrition",
"nutrition",
"physical activity",
"double burden of malnutrition",
"social and behaviour change communication",
"programmes"
],
"content": "Introduction\n\nThe co-existence of all forms of malnutrition including wasting, stunting, micronutrient deficiencies and overweight and obesity-known as the triple burden of malnutrition is prevalent in many low-middle-income countries,1 including India.2 An estimate from 129 countries shows, 57 countries are experiencing an existence of both ‘undernourished children’ and ‘overweight adults’.3 In India, successive rounds of the ‘National Family Health Survey (NFHS)’ have revealed a double burden of malnutrition, across all age groups4,5 and micronutrient deficiencies among children and adolescents (0-19 years).6 This is worrisome, as all the critical stages of life get affected, including early childhood, adolescence, pregnancy and lactation. Childhood obesity is associated with a higher chance of premature morbidity, death and disability in adulthood.7 Likewise, maternal obesity during pregnancy is associated with increased risks of adverse maternal, foetal, and childhood outcomes,8 underscoring its significance as a public health concern. Maternal obesity has even been associated with decreased initiation of breastfeeding, reduced duration of breastfeeding, along with inadequate milk supply compared with their normal weight counterparts.9\n\nThe drivers of overweight and obesity occur at the individual level (age, gender, inadequate physical activity, unhealthy food habits, undernutrition in early life, nutrition literacy and increased screen time),10–14 interpersonal level (paternal and maternal nutrition status, inadequate breastfeeding practices and early introduction to formula foods,15 education status, household income, socio-economic status, obesogenic home environment),16–18 community (obesogenic food environment, inadequate physical activity environment),18–20 organisational level (obesogenic food environment, inadequate physical activity environment),18–20 and at policy environments (policies that enable or constrain physical activity and healthy eating). This suggest that unhealthy dietary habits and lack of physical activity are not primarily attributed to individual choices, as they are influenced by multiple factors operating across these levels.11 Therefore, to prevent overweight and obesity at all critical ages (children, adolescents, pregnant and lactating mothers), it is crucial to address factors operating across all levels of influence.\n\nIn context to India, the diverse cultural norms exhibit significant regional variations. These patterns are deeply intertwined with lifestyle choices, like eating habits and physical activity which collectively determine energy balance and consequently our body weight.21 Recognising the need for adopting healthier diets and being more physical active are behavioural challenges that are pivotal aspects of combating obesity.11 The cost effectiveness of Behaviour change communication techniques is reported to be higher for obesity prevention compared to their application in management and treatment.22,23 Social and Behaviour Change Communication (SBCC) is a recent, yet widely recognized approach that emphasises on improving health outcomes through strengthening social context, i.e. improving behaviours of individuals and groups by addressing key drivers that shape these behaviours across various levels of influence.24 A systematic review has highlighted the effectiveness of SBCC in preventing and reducing stunting and anaemia,25 indicating its potential in addressing various health risk. This approach has also shown to be successful in tackling breastfeeding and complementary feeding,26 indicating that SBCC can and do succeed in improving the uptake of those practices. While it is crucial to recognize the effectiveness of SBCC in addressing overweight and obesity in India, there is currently a lack of a scoping review that examines the role of SBCC within existing policy instruments aimed at tackling this issue. Understanding the extent to which current policies integrate SBCC approaches to address overweight and obesity in India is essential yet remains unexplored in available literature. To address this gap, we conceptualised a scoping review to: 1) map existing policy instruments, including national programmes, schemes, regulations and guidelines that address overweight and obesity in India to understand the extent of national action; 2) evaluate the extent and nature of SBCC strategies employed alongside these policy instruments and; 3) offer recommendations to prevent overweight and obesity in India using SBCC techniques.\n\n\nMethods\n\nTo map the current national policies that address overweight and obesity in India we adopted ‘Arksey and O’Malley’s’ five stage scoping review framework.27\n\nIdentifying research question\n\nWe started by identifying the broader purpose of examining the existing policies related to overweight and obesity, nutrition, health in India, aiming to understand how SBCC are integrated within these policies. Moving forward, our focus shifted to assessing the extent of existing policies covering overweight and obesity only. This involved examining national programs, schemes, regulations and guidelines. Additionally, we sought to understand the methods, mechanisms and approaches to how SBCC strategies incorporated alongside these policies. Based on these inquiries, we consolidated the data into a single comprehensive question, to align with the objectives of the scoping review.\n\n“(1) What is the extent of existing policy instruments, including national programmes, schemes, regulations, and guidelines, addressing overweight and obesity in India, and (2) how are SBCC strategies integrated alongside these policies?”\n\ni. Identifying relevant policies\n\nOur search strategy initially involved listing of all central government Ministry websites (n=49) in India. From there, we compiled a comprehensive list of all potential government websites pertinent to health, diet, nutrition, and public policy (n=7). Subsequently, these websites were then systematically scanned for policies including programme, schemes, regulations and guidelines addressing the aspects of diet”, “nutrition”, “undernutrition”, “malnutrition”, “overnutrition”, “Double Burden of Malnutrition (DBM)”, “physical activity”, “overweight”, “obesity” in India.\n\niii. Selection of Policies: Inclusion criteria\n\nThe systematic selection of policy instruments was conducted based on predefined inclusion criteria i.e. policy instruments that addresses obesity directly or indirectly either through a focus on nutrition and/or physical activity as a primary or secondary objective and targeted pregnant, lactating women, children (0-5 years and 5-9 years age groups), or adolescents (10-19 years) nationally. Policy instruments with a focus on preventing or treating specific diseases, such as micronutrient deficiencies or wasting and stunting, were excluded. The methodology is schematically outlined in Figure 1. The search was conducted by researchers between March-June 2023.\n\niv. Collating, summarizing, and reporting results\n\nFollowing the identification of relevant policy instruments, we collated, summarised findings from the review process. Seventeen policy instruments with a focus on malnutrition and targeting pregnant women, lactating women, children and adolescents (0-19 years) were identified (n=7). Out of the 17 identified policies, eleven were excluded as they addressed wasting, stunting and micronutrient deficiencies. The excluded policy instruments were ‘Integrated Child Development Scheme (ICDS),28 Infant Milk Substitute, Feeding Bottles and Infant Foods (Regulation of Production, Supply and Distribution) Amendment Act, 2003 (IMS Act),29 Janani Suraksha Yojana (JSY),30 Scheme for Adolescent Girls,31 Janani Shishu Suraksha Karyakram (JSSK),32 National Food Security Act,33 Rashtriya Bal Swasthya Karyakram (RBSK),34 Mothers’ Absolute Affection (MAA) for Infant and Young Child feeding,35 Maternity (Amendment) Benefit Act,36 Poshan Abhiyan (National Nutrition Mission),37 Pradhan Mantri Poshan Shakti Nirman’ scheme (PM POSHAN).38 Six policy instruments were included in the analysis. The programmes (n=3) included in the analysis were Rashtriya Kishor Swasthya Karyakram (RKSK),39 Eat Right India,40 Ayushman Bharat [School Health and Wellness Programme and Pradhan Mantri Jan Arogya Yojana (PM JAY)],41 that focused on all forms of malnutrition - wasting, stunting, micronutrient deficiencies and overweight-obesity; and remaining three (n=3) i.e. Fit India Initiative,42 Food Safety and Standards (safe food and healthy diet for school children) Regulations,43 and National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD)44 focused on aspects of overweight-obesity (Figure 1). The implementation of these programmes spanned from the year 1975-2023.\n\nv. Mapping of data\n\nFor all policy instruments addressing overweight or obesity, we categorised their SBCC strategies using the ‘Socio-ecological model’ (SEM) framework,11 to understand the type and levels of influence that the SBCC strategies may have on dietary and/or physical activity behaviours.\n\nThe SEM framework was chosen as it is a widely recognised and established framework for comprehending the intricate interplay between individual behaviour and the social and environmental factors that shape these behaviours.11,45 It serves as a valuable tool for developing behaviour change interventions due to its ability to provide a profound understanding and insight into various levels of interactions between individuals, and their environment within a social system. This framework comprises of five levels, namely, individual, interpersonal, community, organisational and policy environment. At the individual level, the framework reviewed how knowledge, attitudes, behaviours, and skills influence an individual’s actions. The interpersonal level focuses on an individual’s relationships with other people, such as family, friends, or peers. The community level explores strategies for connecting or reaching to a broader audience. The organisation level looks at structures like schools, workplaces, cafes, restaurants etc. to support the adoption of rules and policies for adopting or inculcating healthy behaviours.11 Similarly, the enabling policy environment focuses on approaches adopted by the government to address the needs of larger populations by introducing laws, policies, and legislations to encourage the adoption of healthy behaviours. Table 1 presents how each policy instrument addressed overweight or obesity and describes the SBCC strategies used, according to the SEM (Table 1).\n\n\nResult\n\nWe found 17 policy instruments, out of which eleven were excluded. The remaining six were assessed for multifaceted interventions employed at different levels of influence as per SEM framework as below.\n\nThe “Rashtriya Kishor Swasthya Karyakram (RKSK)” launched in 2014, aims to provide a holistic continuum of care to adolescent girls and boys with emphasis on marginalised and underserved groups. The programme encompasses six priority areas including nutrition. The behavioural strategies of the programme targets adolescents in schools, families and communities through multiple strategies using outreach by counsellors, facility-based counselling, and strengthening of adolescent-friendly health clinics across levels of care.39 SBCC activities were identified across all levels of the SEM under RKSK.\n\nIndividual level: Adolescent Friendly Health Clinics (AFHCs),46 are to be established for providing individual counselling to adolescents, on various adolescent health issues including diet, with help from trained counsellors, Auxiliary Nurse Midwifery (ANMs) and Medical Officers at Government Medical Colleges, District Hospitals, Community Health Centres, and Primary Health Clinics. Counselling aims to improve adolescents’ knowledge and adoption of healthy behaviours (including diet and physical activity), dissemination of pamphlets, handouts and display of posters at AFHCs. These clinics needs to be established close to adolescents to enhance access to services, thereby increasing uptake and demand through the dissemination of messages and materials on behaviour change communication.46\n\nInterpersonal level: Interpersonal communication with adolescents at village level is enabled with the help of Peer Educators (PEs).46 Weekly participatory sessions with adolescent group (comprising of 15-20 adolescents per group) are to be conducted (including with out-of-school adolescents). In addition, Adolescent Friendly Club meetings, comprising 10-15 PEs are to be organised monthly to discuss and clarify adolescents’ health issues with ANM.46 The PEs are trained for six days and during this training one entire session focuses on diet and physical activity.47 A means of interpersonal communication channel, which involves referrals between various centres, de-addiction centres and Non-Communicable Disease Clinics (NCD-clinics) (providing counselling to adolescents and their family members on healthy lifestyle) is recommend to be established to connect AFHCs with ‘school going’ adolescents and referrals for ‘out-of-school’ adolescents through Rashtriya Bal Swasthya Karyakram).48\n\nCommunity level: Mass communication using hoardings, banners, posters (at AFHCs, community, and schools), social media, telecom-based platforms (Saathiya Salah app49) and helplines are to be conducted to maximise programme reach. At community level, institutional approaches include involving teachers, counsellors, PEs and representatives of Non-Government Organisations (NGOs) in promoting adolescent health and wellness. As per RKSK operational guidelines, Adolescent Health and Wellness Days (AHWDs) need to be organised quarterly at the village level where health check-ups of adolescents and many infotainment activities like plays, nritya natak (dance drama) etc are to be conducted. AHWDs aims to generate awareness among adolescents, parents and the community on adolescent health issues including nutrition and prevention of NCDs.50 Information and services including delivery of nutrient supplements i.e. prophylactic dose of Iron Folic Acid tablets and Albendazole for deworming; health screening including clinical testing and screening for anaemia and assessing Body Mass Index for adolescents; counselling on nutrition and balanced diet, cooking using local, seasonal produce are recommended for adolescents in the community during AHWDs.50\n\nOrganisational level: Under the programme, schools are initiated to play a paramount role in becoming centres of health advocacy and delivery. Peer Education sessions are recommended to be implemented in schools with nodal teachers responsible for facilitating and monitoring. Community Health Centres/District Hospitals are expected to organise and conduct outreach services for adolescents and their parents, potentially at schools and colleges. The Adolescent Education Programme is expected to cover all secondary and senior secondary schools in the country, with trained teachers to provide health education on NCDs, nutrition, health and education, violence, substance abuse, etc. in schools.51\n\nEnabling environment/policy level: A National Adolescent Health Strategy has been developed to guide the programme with nutrition as one of the six identified themes (Reproductive and Sexual Health, Nutrition, Mental Health, Injuries and Violence including Domestic and Gender Based Violence, Substance Misuse, Non-Communicable Disease) under the RKSK.52 It emphasises on a holistic and comprehensive model based on a continuum-of-care approach, implemented in collaboration with relevant ministries and state governments.\n\nAyushman Bharat Yojana or the National Health Protection Scheme is a flagship programme launched by the Government of India in 2018.53 It aims to provide healthcare services and insurance coverage to every individual, especially the poor and vulnerable. It provides a defined benefit cover of Rs. 5 lakhs (Rs 0.5 million) per family, per year, and aims to create a comprehensive network of healthcare delivery (especially primary healthcare services) and wellness infrastructure across the country. Until 29 December 2022, 0.15 million ‘Health and Wellness Centres’ have been operationalised to provide reproductive, maternal and child health services along with drug distribution, promotion of balanced, healthy diets and regular exercise, yoga and the usage of digital technology to provide a continuum of care.54\n\nThe School Health and Wellness Programme (SHWP) under Ayushman Bharat was also launched in 2018 to strengthen the preventive and promotive aspects through health promotion activities. Under the School Health and Wellness Programme, a curriculum on nutrition has been included in the year 2018, and nutrition health education is provided to school children to influence their behaviour regarding health and wellness.55 We have considered SBCC activities under both, Ayushman Bharat and School Health and Wellness Programme for SEM analysis, as both include activities for promoting healthy weight.\n\nIndividual level: Home visits are to be conducted by Accredited Social Health Activist (ASHA) workers (female) and Multipurpose Workers (MPWs, male) to screen and counsel individuals on lifestyle modifications including adopting healthy diet, engaging in regular exercise, and addressing communicable and NCDs. ASHA workers are trained to deliver health advice on diet and physical activity, as part of their curriculum.56 Additionally, ANMs assist in taking measurements, such as Body Mass Index indicators, during Adolescent Health and Wellness days (AHWDs) to screen adolescents.50\n\nInterpersonal level: Family education and counselling are to be provided by ASHA workers, especially to pregnant women. Information provided to pregnant women cover nutritional requirements during pregnancy and for new mothers, information on early breastfeeding and complementary feeding practices.54 Nutrition counselling for adolescents and women of reproductive age aim to addresses issues of low birth weight in new-borns and promotion of early initiation of breastfeeding to prevent childhood illnesses, prevention of anaemia, consumption of iron folic acid supplements. The formation, handholding and functioning of patient support group (disease-based) meetings are also part of the programme.57 These groups not only involve patients but also their family members. Family health folders are to be maintained by ‘Health and Wellness Centre’ or nearby ‘Primary Health Centre’. Additionally, under the school health and wellness programme, two teachers in the school are to be trained to become ‘Health and Wellness Ambassadors’ for further imparting age-appropriate information sessions to students. These students can then act as ‘health and wellness messengers’ and engage in health promotional outreach activities to support their peers, parents and family. The programme also focuses on promoting yoga in schools among middle and high school children, particularly on International Yoga Day, through Health & Wellness Ambassadors.57\n\nCommunity level: The programme facilitates community engagement via community platforms such as Village Health and Nutrition Days (VHSND), Village Health, Sanitation, Nutrition Committees (VHSNCs), and the Mahila Arogya Samities (are all women groups). These community groups and committees aim to generate awareness on locally relevant issues such as, lifestyle modifications for maintenance of a healthy diet and regular exercise to prevent cardiovascular diseases and diabetes. Additionally, the community platforms recommend organising periodic meetings and health camps to further promote health messages. Community Health Officers (CHOs) play an active role in health promotion, ensuring counselling, service support and monitoring of health promotional activities.54 Under the RKSK, the Adolescent Health Days have been re-branded as ‘Adolescent Health and Wellness Days’ and ‘Yuva Samvad’ under Ayushman Bharat as Health and Wellness Centre (AB-HWCs). These events are scheduled quarterly with the involvement of primary healthcare teams from AB-HWCs. They serve as edutainment platform to educate adolescents, families and other stakeholders on adolescent health issues including healthy eating, exercise and services available at AB-HWCs.50\n\nOrganisational level: Under the programme, two teachers in every school are to be trained to become ‘Health and Wellness Ambassadors’. These “Health and Wellness Ambassadors” in schools are also designated to plan age-appropriate, skill-oriented, theme-based sessions for children who can further act as ‘Health and Wellness Messengers’.57 Among the various themes for health promotion, two themes relate to overweight and obesity, specifically, ‘improving nutrition’ and ‘addressing conditions of NCDs ’.51 Weekly, ‘Health and Wellness Days’ in schools are to be observed on Tuesdays.57 Under the programme, counselling services at schools are to be made essential.50\n\nEnabling Environment/Policy level: The HWCs formed under ‘Ayushman Bharat’ are supported in the National Health Policy, 2017.58 The policy recommends strengthening the delivery of Primary Health Care through the establishment of “HWCs” as the platform to deliver Comprehensive Primary Health Care.\n\nThe Food Safety and Standards Authority of India (FSSAI) as mandated in the preamble to the Food Safety and Standards Act, 2006, is tasked with ensuring the availability of safe and wholesome food for the Indian population. In pursuit of this objective, FSSAI initiated the ‘Eat Right India’ movement in 2018, aiming to revolutionize the nation’s food system to provide safe, healthy, and sustainable food for all citizens. Anchored by the tagline “Sahi Bhojan. Behtar Jeevan (Eat Right. Better Life),” this movement combines regulatory measures, educational campaigns, capacity-building initiatives, and collaborative efforts. Like other initiatives, Eat Right India endeavors to instigate behavioral change by addressing all levels of the Socio-Ecological Model.59 Similar to other programmes, Eat Right India also intends to change behaviour by targeting all levels of Socio Ecological Model.\n\nIndividual level: Education and awareness on food safety, nutrition (safe and sustainable diets) and hygiene is to be imparted among children in schools via Eat Right school programme.60 Content like a Yellow Book (age appropriate books, in two volumes with each of them targeted at children from grade 1-8 to inculcate the right eating habits and are available in 11 languages),61 a fun-filled activity book has been designed to teach and reinforce the message of safe and nutritious food, videos,62 posters63 and a food safety magic box (manual on easy tests for checking adulterants in food)64 have been developed for integration into the school curriculum. ‘Health and Wellness Ambassadors’ (teachers) and teams (School Health Clubs) are to be made in schools to carry out Eat Right activities in schools. A teacher training manual was developed to give an in-depth understanding of the concepts of food safety and nutrition.61\n\nInterpersonal level: Parents are encouraged to be ‘health and wellness ambassadors’ by taking up an online certification course on food safety and healthy food by FSSAI, to sensitise others.65\n\nCommunity level: Community-based competitions like ‘low salt cooking competition’, quiz,66 mela (fair),67 challenges68,69 and paint a wall are to be organised to spread positive messages. A mobile food testing van- ‘Food Safety on wheels’70 has been launched to access remote areas and conduct training and awareness activities. Eat right ‘tool kits’ have been developed to reach communities at the grassroots level. Education and awareness on food safety and nutrition is to be imparted to individuals in communities with the help of developed toolkits by frontline healthcare workers.40 The toolkits are developed on two broad components - ‘Eat Healthy’ and ‘Eat Safe’. It attempts to deliver clear and simple messages on foods to eat (balanced diet, fortified foods, nutrition during the first 1,000 days) and foods to avoid (high fat, sugar and salt foods) and elimination of trans-fats from our diets.40\n\nPublic Service Announcements (PSAs), video, flyers, flipbooks, posters, social media and celebrities to be used to generate awareness among people to adopt dietary modification for healthy eating, for example – “Aaj Se Thoda Kam” starring Indian celebrities to reduce HFSS food intake, ‘Trans-Fat Free India@75’ and ‘Heart Attack Rewind (against use of trans-fat) and promotion of food fortification.71 Furthermore, mascots ‘Miss and Master Sehat’72 to be utilized to spread awareness on safe and nutritious food in community.73 Awareness campaigns on the importance of food fortification (adding important vitamins and minerals to food items) are to be implemented.74\n\nOrganisational level: Many schools, colleges, workplaces, hospitals, etc. are encouraged to become a part of ‘The Eat right campus’75 initiative to promote safe, healthy and sustainable food on campuses across the country. Mascots ‘Miss and Master Sehat’72 are used to spread awareness on safe and nutritious food in education institutes.76,77\n\nEnabling Environment/Policy level: There are many regulations passed under the Eat Right India initiative, for example, the Repurpose Used Cooking Oil (RUCO)78 that requires all Food Business Operators (FBOs) to monitor the quality of oil during frying (limit for Total Polar Compounds at 25 percent beyond which the vegetable oil) by complying with the regulations from 1st July 2018 onwards; Packaging regulations(2019)79 that provide guidelines for businesses looking to verify packaging materials and processes that are safe for food have been passed.80 Voluntary public commitments made by individual chefs, bakeries and their associations are encouraged to commit to eliminating industrial trans-fat from their products to safeguard the health of the Indian citizen and provide them with healthy food environments.81\n\nThe Fit India Movement was launched in August 2019 by the Indian government to make fitness an integral part of our lifestyles by promoting physical activity.42 It is a nationwide campaign with activities suited for people of all age groups. This initiative is comprehensive with SBCC strategies at all levels of SEM.\n\nIndividual level: A mobile application called ‘Fit India App’,82 has been launched by the Government of India for all individuals to enable fitness and diet monitoring. Through this Mobile App, citizens can assess their fitness through a series of simple tests and are provided with regular information on how to improve their fitness levels. Additionally, the Fit India Mobile App has features such as setting daily activity and fitness goals and trackers to monitor daily activity, water intake, calorie intake and sleep.\n\nInter-personal level: Fit India Movement encourages “Youth Clubs” to motivate and harness youth to become part of Fit India Movement, to create mass awareness on the importance of physical activity. Fit India Youth clubs are a registered group of people who are aware of the importance of physical activity and who can motivate fellow citizens to get involved in 30-60 minutes of physical activity per day for five days a week. Youth clubs are motivated to inculcate approximately 60 minutes of physical activity in their daily plans, five days in a week.\n\nCommunity level: As a part of the Fit India Movement, positive messages through dialogues and conversations on nutrition, and wellness with prominent sports personalities, health icons, influences, and health ambassadors are aired via various mediums (hoardings, banners, posters, television advertisements, social media- Instagram/YouTube etc) to motivate people to implement activities like the “Fit India Freedom Run’83 and, ‘Fit India Cyclothon’. At the community level, the Fit India Freedom Run, Plog Run (the activity of picking up trash while jogging), Cyclothon, and cycle rallies are to be organised.\n\nOrganizational level: Under the ‘Fit India school campaign’,84 schools are encouraged to apply for Fit India School Certification that necessitates having atleast one teacher trained in Physical education, having a playground where two or more outdoor games can be played, having atleast one physical education period each day. It also necessitated having a physical activity hour (minimum of 60 minutes per day) for every child within schools.85 The school is provided with certification when they satisfy the physical activity criteria laid down by the government. Parents, staff and school management committee members are encouraged to actively participate in club activities to act as role models for students. ‘Fit India School Week’86 is observed in all enrolled schools to promote messages through competitions like poster-making, poetry recitation, essay competitions, graffiti competitions, lectures and cultural events on topics related to physical activity and healthy eating. Schools are encouraged to celebrate ‘Yoga day’, ‘fitness day’, ‘pledge of fitness’ and ‘annual day during sports week culmination’. Workplaces are also included in the Fit India Movement, with businesses encouraged to organise weekly sports activities and open gym facilities for their employees at their workplaces. ‘Fit India Prabhat Pheri’ (morning walks)83 by small as well as larger organisations like Resident Welfare Associations, Village, Town or City Council/Panchayat/NGOs are encouraged.\n\nEnabling policy environment: Under the Fit India movement, the government has mandated a physical education period per day for every child in public and private schools under the Central Board of Secondary Education.87 Fit India protocols have also been generated for all citizens of different age groups.88\n\nThe Food Safety and Standards (Safe Foods and Healthy Diets for children in School) Regulation applies to schools and crèches, and focuses on the provision of safe and healthy food to children and adolescents (> 22 months - 18 years).43 According to our analysis, there are no SBCC strategies embedded in this regulations that cater to individual, interpersonal and community levels but concurrently, Organisational and Enabling environment/Policy level exist as per SEM.\n\nOrganisational level: The regulation states that 75-80% of the food available in school canteens should belong to the ‘healthy food groups’ i.e. cereal, millets and pulses, milk, milk products, egg, meat and fish, fruits and vegetables, oils, fats, nuts and oilseeds, processed/cooked foods. HFSS foods should not be made available or advertised on school campuses and areas within fifty metres from the school gate.43 Schools are encouraged to engage with nutritionists to draft healthy menus for children. In addition to a well-balanced menu with a variety of foods in the school cafeteria, food labelling and display of healthy food options are encouraged under the regulation. The regulation necessitates, school authority to ensure that signage boards containing warning “Do not sell including free sale or market or advertise the food products high in saturated fat or trans-fat or added sugar or sodium within school premises or campus” are prominently displayed at the school gate.43\n\nEnabling environment/policy level: The regulation states meal times in schools to mandatory inculcate healthy eating habits in children. Under the regulation, guidelines, related to permitted foods and beverages and the quantity (to promote use of cooking oil in moderate amounts) and quality (e.g., use of re-heated fats and oils shall be avoided) are issued. FBOs manufacturing are also barred from advertising and marketing of HFSS foods and beverages to children on school premises, including through logos, brand names, posters, textbook covers or in an area within fifty meters from the school gate in any direction. Sponsorships of sporting events in schools by FBOs can only be done if their foods are not HFSS.43\n\nNP-NCD, also previously known as National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS)89 was launched in 2010 in 21 districts and expanded pan India in 2017.90 It focuses on strengthening infrastructure, human resource development, health promotion (especially for 18 years and above), early diagnosis, management and referral, especially for the population aged 30 years and above. The programme offers a range of services including health promotion, psychosocial counselling, management (out-and-in-patient), day-care services, home based care and palliative care as well as referrals at various health facilities. It is also the first programme that talks about the need for health education programmes that promote exercise, weight reduction, early diagnosis, screening and management of individuals with NCDs with addressing their risk factors at health facilities.44 The programme targets majority of SEM levels i.e. individual, inter-personal, community and organisational.\n\nIndividual level: Under the programme, the community health workers (ASHA/MPH/ANM) are to impart health education on healthier lifestyle behaviours like, healthy eating and physical activity to individuals. Opportunist screening of individual (above the age of 30 years) to identify individuals at risk of NCD is on basis of Community Based Assessment Checklist (CBAC)91 which encompass waist circumference measurement along with other at risk parameter of NCD by community health workers at PHCs. ASHAs are to capture enumeration and CBAC for all individuals above the age of 30 years at household level during house visits. An NCD application (CPHC-HWC App)92 has been developed for enumeration and to perform risk analysis of the enumerated individuals.93 The appointed counsellor at Community Health Centres (CHCs)/PHCs, Sub-Centres and District Hospital (DH), are expected to provide counselling to the patients (>30 years) on increased intake of healthy foods, increased physical activity through sports, exercise, etc., at the time of their visit to health facility.44\n\nInter-personal level: Counselling of patient’s attendants/family members, who come along with the patient on healthy lifestyle (healthy diet, physical activity, salt reduction, avoidance of alcohol and tobacco) is to be carried out along with the patient to bring about effective inter-personal communication. The frontline community health workers are also to provide family centric care and education on adoption of healthier lifestyles and treatment under NP-NCD.44\n\nCommunity level: Camps are to be organised in the village, on VHSNDs when the health worker goes to the village for immunization and other health services. During these camps/designated days, health workers are expected to discuss the various aspects of healthy lifestyle and its benefits with the target groups and motivate them to adopt healthy lifestyle and to practice regularly for the prevention of common NCDs. Key messages that need to be conveyed to the public include: 1. increased intake of healthy nutritious foods 2. Increased physical activity through sports, exercise etc. During the camps/designated day, ANM and (or) Male Health Worker are expected to record history of persons at and above the age of 30 years for physical activity and Body Mass Index etc. (via CBAC- opportunistic screening) and provide referrals to at risk individuals. Opportunistic screening for NCD including waist circumference under CBAC forms is also required by the health workers.94 Yoga is also an integral part of the programme. Under the programme, observance of NCD Week/Fortnight (Swasth Nagrik Saptah/Pakhwara) is also suggested to be organised as a platform to increase awareness regarding NCD and campaign like K4H-Knowledge for Health for NCDs.\n\nHealth promotion on a healthy lifestyle (healthy diet, physical activity, salt reduction, avoidance of alcohol and tobacco) is to be carried out in the community. Locally prevalent folk media (street plays, wall paintings, hoardings etc.) is recommended to be used to reach the targeted population, particularly in rural and urban deprived population.\n\nThe programme talks about using mass media for health promotion. Public awareness using the most effective channels (Radio, Television, Internet and Print media- pamphlets and hand-outs) that have reach to the community are recommended to be used for health promotion. There is also a plan to utilise m-Health strategies for expanding access to health information on NCDs. m-Diabetes and m-Cessation interventions have been integrated for health promotion.44\n\nOrganisational level: Women self-help groups/social groups and NGOs are recommended to be used for health advocacy. Health promotion activities to be carried in schools, workplaces, during VHSNCs, Mahila Aarogya Samiti and Jan Aarogya Samiti etc. under the programme.44\n\n\nDiscussion\n\nThis paper investigate the SBCC strategies employed by the existing policy instruments in addressing overweight and obesity in India among children, adolescents, pregnant and lactating women. The outcomes of our study are significant as rising obesity rate pose a considerable public health issue in India95,96 and are recognised as major contributor to disability and death, globally.97\n\nOur scoping review revealed that before the year 2023, none of the policy instruments notably addressed the rapidly rising burden of overweight and obesity across various age groups (including pregnant women, lactating women, children and adolescents). However, the introduction of NP-NCD in 2023 marked a pivotal shift in our country’s approach to tackle obesity, as it recognises the intricate linkages between obesity and NCDs and underscores the significance of addressing obesity through a behavioural change approach. Among the six identified policy instruments, the recently revised NP-NCD programme44 has the potential to serve as a comprehensive approach for tackling the escalating burden of obesity within the broader context of NCDs.\n\nThe growing prevalence of overweight and obesity across all age groups has led to an increased focus on implementing triple duty actions, regulating the advertisement of HFSS foods, necessitating changes in governance, financial strategies, and capacity building.98 The Lancet Commission on the global syndemic of obesity, undernutrition, and climate change also highlights the need to concurrently address these interconnected problems.99 Considering the triple burden of malnutrition, and aligning with Target 2.2 of the Sustainable Development Goals, which aims to “end malnutrition in all its forms”,100 the Indian government has taken applaudable steps to confront this emerging issue, by formulating the ‘Multisectoral Action Plan for Prevention of Non-Communicable Diseases’101 (2017-2022) with a special emphasis on prioritizing obesity prevention. This approach aligns with efforts in other countries like Ethiopia, Tanzania, United Kingdom, Kingdom of the Netherlands, where SBCC strategy action plans tailored to health and nutrition102–105 and Tonga for obesity prevention.103 The revised NP-NDC programme acknowledges the inter-connectedness of various biological and environmental health determinants, emphasising the importance of maximising the impact of interventions.\n\nIn the future, in short term, apart from the NP-NCD programme, enhancing the integration of SBCC strategies into other existing national and sub-national level initiatives could be prioritised. Given the evolving landscape of malnutrition within the country, transitioning from stunting and wasting to triple burden of malnutrition; it is imperative to incorporate triple duty SBCC messages, campaigns, and interventions related to diet, services, and caregiver practices into programmes initially intended to address only stunting and wasting.\n\nFuthermore, double duty action could be integrated into India’s recently launched Integrated Nutrition Support Programme i.e. Saksham Anganwadi and POSHAN 2.0.106 This initiative could incorporate an exclusive plan to address overweight and obesity alongside efforts to combat malnutrition. POSHAN 2.0 presents an opportune platform, as it targets the strategic age group and seeks to develop and promote practices that nurture health, nutrition awareness and good eating habits for sustainable health and wellness and immunity in the community.106\n\nIn the long term, allocating resources, both in terms of time and budget, for a national campaign targeting overweight and obesity is recommended. This initiative could entail partnering with leading communication firms known for their successful marketing strategies, extending even to remote areas. The existing NCD Divisions at the national, state and district levels that focus on the promotion of healthy diets and practices among population under NP-NCD could consider development of overweight-obesity guidelines including focus on healthy eating practices, toolkits etc. for the population. While certain existing policy instruments have included this to some extent, there is room for more systematically and wide-reaching efforts so that all forms of malnutrition are brought to the same level of concern and attention as stunting, wasting and micronutrient deficiencies in the public sphere. This can be achieved by addressing its various underlying cause, with particular focus on caregivers (families, parents especially mothers) and communities at large. Actions and strategies need to be ‘well-resourced’ at all levels by improving the provision of resources (both human and monetary). These campaigns should be developed based on assessment of the prevailing behavioural patterns in the country, along with a thorough understanding of the underlying reasons for same. Additionally, it is important to allocate dedicated budgets for SBCC activities. Providing definitive budget commitments, clear and realistic time-bound strategies, along with a robust monitoring and evaluation frameworks can contribute to efficacy and sustainability of the activities.\n\nSBCC strategies must be supported by actions at the policy level to create an enabling policy environment. For example, the effectiveness of SBCC strategies can be strengthened through comprehensive actions that provide both i.e., enforcement of SBBC strategies and mandates that lead to environment improvements which nurture behaviours.107–109 For the matter, a commendable action taken in India has been the FSSAI, MOHFW ban on the sale and marketing of HFSS foods within schools and a 50 metres radius of the schools’ perimeter.110 Such a policy can augment nutrition related SBCC strategies within schools by promoting an environment in schools where it is easier for students to put into practice what they learn. Another potential enabling policy for SBCC strategies could be subsidising healthy foods and increasing taxation on HFSS, as currently, healthy food options are more expensive than unhealthy foods in India.111 A study conducted in seven countries found that subsidies on healthier food lead to a significant increase in the purchase and consumption of healthier food options.112 There is a need to modify food labelling norms in India, for example, easy to understand front-of-pack labelling could potentially improve consumers’ food choices.113 Mandatory front-of-pack labelling, easy-to-read labels (descriptive labelling) or health warnings on labels need to be introduced by the relevant authorities. Additionally, initiatives to empower the consumer to identify and understand these labels correctly need to be conducted to promote behavioural changes.114 Other possible measures include reducing serving size,115 plate size in restaurants, serving healthier items as welcome snacks and drinks, default vegetable and fruit in combination meals in fast food places, monitoring the quality and quantity of cooking oil in dishes at fast food chains and restaurants, similar to the FSSAI’s RUCO78 initiative for small FBOs.\n\nTransitioning to the organisational level, the Government of India has made commendable efforts to address overweight and obesity through initiatives such as School Health and Wellness programme57 under Ayushman Bharat. The programme aims to inculcate appropriate health and nutrition behaviours in school children.57 Implementing simple efforts like having a fruit and vegetable policy in schools for a food break, significantly increases fruit and vegetable consumption in children.116 Poshan Vatika’s or nutri-kitchens (community kitchen gardens), as planned under POSHAN 2.0, aim to encourage the use of locally available products to avoid malnutrition. A similar approach can be adopted in Indian schools through meaningful engagement of students. An increased intake of vegetables among students involved in creating schoolyard gardens was evident from a study conducted in United States.117 Descriptive labelling and attractive packaging of healthy food items can also be implemented in Indian schools to support behaviour change towards the consumption of healthy foods in schools cafeteria’s.118 Furthermore, promoting availability of healthy eating options at public places119–121 like cinemas, cafeterias, and gyms, can have a significant impact on an individual’s food choices, especially in the Indian context to promote the consumption of healthy eating among all age groups. Simultaneously, there is a need to provide physical activity infrastructure in schools, colleges and workplaces and other organisational settings to facilitate opportunities for increasing physical activity levels among children, adolescents, youth and adults.122 My Plate for the Day’, developed by the Indian Council of Medical Research-National Institute of Nutrition (ICMR-NIN), MoHFW is designed on the basis of ‘Dietary Guidelines for Indians’ and ‘Nutrient Requirements for Indians’ to encourage and promote healthy dietary practices among the community.123 The model plate is aimed to provide dietary diversity with a proper balance in macro- and micro-nutrients for a healthy individual of any gender.124\n\nWe identified numerous initiatives undertaken by the Government of India to promote healthy lifestyles, especially physical activity among citizens at the community level like, the Fit India Movement,125 community and individual counselling under NP-NCD, observing International Yoga Day, National Youth Day126 and International Day of the Adolescents. These initiatives demonstrate the importance of strong political commitment to prioritizing essential preventive health strategies for the population at large. Within these programmes, various communication tools such as flyers, infographics, health cards, cooking demonstration sessions, digital resources and discussion groups must have messages that are context-specific, non-technical, and delivered in local dialects. To promote physical activity, it is essential to enhance accessibility and infrastructural modifications in spaces such as public parks to encourage physical activity for people of all age group.\n\nThe use of digital approaches to healthcare and prevention are increasing, particularly in low-middle-income countries.127,128 The use of mobile health tools129 to educate people in remote and hard-to-reach areas about nutritional counselling and physical activity has already been planned under the NP-NDC. However, the programme can significantly enhance its reach and effectiveness by targeting all community members by using new innovative social media activities like reels, WhatsApp messages, health quiz challenges, storytelling, interactive sessions etc. Social marketing can be integrated into multi-level ecological approaches, utilising multiple “P” (Price, Place, Product and Promotion) intervention strategies to support environmental changes that promote healthy behaviours in children.130 Health promotion messages in-between advertisements can be developed and broadcasted in programmes and channels with children shows, as in the ‘CNN-BBC network joint campaign on health promotion messaging on coronavirus”.131 Nutritional counselling of parents using m-health technology can also be provided. This approach is supported by the success of an Australian childhood obesity prevention internet based-programme for parents, which demonstrated improved dietary practices in children due to parental e-health counselling.132 Technology can also be utilised for screening children for obesity in schools and institutions, aiding early identification and promoting overall health and wellbeing.133\n\nMoving forward, there is a critical need for robust research guided by Behavioural Insight Unit of NITI Aayog, the apex public policy think tank of the Government of India.134 This research aims to gain better insight into drivers of obesogenic behaviours and identify potential nudges that can influence various segments of the population, including, children, adolescents, pregnant and lactating mothers. It is essential to understand the determinants specific to both rural and urban areas. Such research endeavours planned under the NP-NCD programme, would significantly contribute to build substantial evidence in combating overweight and obesity. However, it is noteworthy that scoping reviews provide a broad overview and are susceptible to bias and thus future research could take up a more in-depth research especially on grassroot implementation of planned SBCC strategies under programmes.\n\n\nConclusion\n\nThe scoping review underscores the immense potential of India’s NP-NCD programme in addressing the formidable challenge of NCD, while also emphasising on overweight and obesity prevention, due to its comprehensive and multi-disease approach. The programme has the potential to impact behaviours and shape societal norms to promote healthier lifestyles. It’s success would hinge on continuous and rigorous enforcement across all its components and creation of supportive policies, regulations and environment that can help foster healthy behaviour in the community.\n\n\nAuthors’ contribution\n\nMA, SB and DB conceptualized the study. NT, DB and SB contributed to scoping review, analysis and interpretation of results. NT, DB, SB, KC drafted the manuscript. KB, NB, SG, SC, LT, PM, PM, MA reviewed the manuscript critically for intellectual content. All authors reviewed and approved the final manuscript.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nKulkarni VS, Kulkarni VS, Gaiha R: Double Burden of Malnutrition.2016 Sep 15 [cited 2022 Dec 30]; 47(1): 108–133. Publisher Full Text\n\nHoque ME, Doi SAR, Mannan M, et al.: Prevalence of overweight and obesity among children and adolescents of the indian subcontinent: A meta-analysis. Nutr. Rev. 2014; 72(8): 541–550. PubMed Abstract | Publisher Full Text\n\nEstle M: Rethinking nutritional policies in developing countries taking into account the double burden of malnutrition.2016 [cited 2023 Mar 22]. Reference Source\n\nInternational Institute for Population, Sciences (IIPS) and Macro International. National Family Health Survey (NFHS-3) 2005-06. Mumbai: IIPS; 2007 [cited 2022 Jun 11]. Reference Source\n\nGovernment of India: National Family Health Survey (NFHS - 5), 2019–21. Mumbai: 2022 [cited 2022 Jun 11]. 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Publisher Full Text Reference Source\n\nVyas S: Social and Behaviour Change Communication – Essential Component of Contemporary Health Care. Heal. J. 2016 [cited 2023 Apr 21]; 7. Reference Source\n\nINTEGRATED NUTRITION INVESTMENT FRAMEWORK (INIF) USAID/Cambodia.2012 [cited 2023 Apr 11]. Reference Source\n\nTull K: Behaviour-change communication on health related issues (part one).2017 [cited 2023 Apr 11]. Reference Source\n\nArksey H, O’Malley L: Scoping studies: towards a methodological framework. Int. J. Soc. Res. Methodol. 2005 Feb [cited 2024 Mar 26]; 8(1): 19–32. Publisher Full Text\n\nMinistry of Women & Child Development: Integrated Child Development Services - ICDS Scheme.\n\nGovt of India: The Infant Milk Substitutes, Feeding Bottles and Infant Food (Regulation of Production Supply and Distribution) Act, 1992. Delhi. Reference Source\n\nMinistry of Health and Family Welfare G of I. Janani Shishu Suraksha Karyakram.\n\nMinistry of Women and Child Developmen government of I. 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}
|
[
{
"id": "303344",
"date": "03 Sep 2024",
"name": "Deepa Handu",
"expertise": [
"Reviewer Expertise evidence based methodologists",
"systematic review",
"scoping review",
"nutrition",
"public health",
"etc"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this article.\n\nI have two major comments for this paper: -Rigor of Methods for Scoping Review: Though the authors state that this is a \"Scoping Review\" and follows Arksey and O’Malley’s steps of conducting a scoping review……………each step of this process is not conducted rigorously and does not meet the methods standard for scoping reviews.\n\n- Also, scoping reviews are conducted to see what is the availability of evidence on a certain topics………….and secondly- how are these findings going to help your future actions? OR how the findings of this scoping review guide your next steps. - the rationale for conducting a scoping review should be strong. - Please link of your findings to stated research questions/objectives.\nSearch strategy needs more details. Did the authors just hand search government files or is there any database of government documents available. Sharing a search strategy is a main component of scoping reviews. Seems like most of their search is “grey literature”- if yes then that should be clearly stated and what other sources of grey literature did they search. How do reviewers confirm they conducted an exhaustive search. A PRISMA flow chart of search should be provided. Also, what were the search dates for these article/policies to be included? Was this scoping review registered anywhere?? Eligibility criteria: how were the articles screened and who screened the articles for inclusion.\nMost of my comments are related to the rigor of the methods, transparency of reporting, and how will the findings contribute to next steps.\nWould suggest that authors refer to PRISMA Scoping Review checklist to help address all the key points necessary for a Scoping review.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No",
"responses": [
{
"c_id": "12775",
"date": "18 Nov 2024",
"name": "Shalini Bassi",
"role": "Author Response",
"response": "Response Document- 1. Rigor of Methods for Scoping Review: Though the authors state that this is a \"Scoping Review\" and follows Arksey and O’Malley’s steps of conducting a scoping review……………each step of this process is not conducted rigorously and does not meet the methods standard for scoping reviews. Response: Thank you for this observation. We have revised the manuscript and detailed description of each step of the scoping review process aligning with the Arksey and O’Malley framework in the methodology and result section added. 2. Also, scoping reviews are conducted to see what is the availability of evidence on a certain topics………….and secondly- how are these findings going to help your future actions? OR how the findings of this scoping review guide your next steps. The rationale for conducting a scoping review should be strong. Please link of your findings to stated research questions/objectives. Response: Thank you! The scoping review map the availability of evidence on how SBCC is integrated into policies on overweight obesity in India. The findings will guide future actions by identifying gaps, informing and suggestion mid-course correction and policy implications. As suggested, the same has been mentioned in the introduction for clarity. Further on as per your suggestion, we have linked the findings to the research questions. 3. Search strategy needs more details. Did the authors just hand search government files or is there any database of government documents available. Sharing a search strategy is a main component of scoping reviews. Response: Thank you! We have edited the search strategy, to provide a more detailed description of the process, enhancing clarity based on your suggestion. Seems like most of their search is “grey literature”- if yes then that should be clearly stated and what other sources of grey literature did they search. How do reviewers confirm they conducted an exhaustive search. Response- Thank you for your valid suggestion. We have edited the search strategy to mention grey literature A PRISMA flow chart of search should be provided. Also, what were the search dates for these article/policies to be included? Response: Thank you! As suggested a revised PRISMA flow chart of the search strategy has been attached with the manuscript as Figure 1. Additionally, the search dates of the policy instruments[1] is already been included in the manuscript. “The search was conducted by researchers between March-June 2023.” 4. Was this scoping review registered anywhere? Response: Thank you for your insightful comment regarding the registration of our scoping review. In our case, the scoping review was not registered anywhere, since our research was primarily exploratory and unlike systematic reviews did not look to assess the impact of any intervention, hence we did not feel the need for registration. Secondly, by the time we considered registering, we had already made significant progress in terms of defining the research question and developing the protocol. Thirdly, research questions and methodologies evolved significantly during the review process, this would have complicated the adherence to any prior registration plans. However, we acknowledge that registering a scoping review is a valuable step to increase transparency and avoid duplication of efforts and will definitely be considered henceforth. 5. Eligibility criteria: How were the articles screened and who screened the articles for inclusion. Response: Thank you for the question. We have elaborated the search strategy as per your suggestion. The policies were screened based on eligibility criteria. Two researchers (NT, DB) conducted the screening process and any discrepancies were resolved through discussion or consultation with a third researcher (SB) to ensure consistency and minimize bias. All have been included in the strategy. [1] Policy instrument’s throughout the paper has been used to cover programmes, schemes, regulations and guidelines"
}
]
},
{
"id": "288622",
"date": "23 Sep 2024",
"name": "Palak Gupta",
"expertise": [
"Reviewer Expertise Food insecurity",
"hunger",
"Nutrition",
"public health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this article. I appreciate the effort put into this work. However, I have a few comments regarding the methods and conclusions.\nMethods: Was this scoping review registered anywhere (e.g., PROSPERO)?\nThe eligibility criteria for inclusion need further clarification. How were the articles screened, and who was responsible for the screening process? This should be clearly outlined to ensure transparency.\nthe methodology could benefit from clarification on how comprehensiveness was ensured. Researchers started with 49 and narrowed to 7 policies. Were there any search terms or Boolean logic used? Did the researchers consult any experts to validate that all relevant ministries and policies were included?\n\nthe decision to exclude policies focused on micronutrient deficiencies and wasting/stunting could be elaborated upon, given the connection between malnutrition and obesity. A more detailed rationale for exclusion would strengthen this section. Also, clarifying whether this exclusion was based on a theoretical framework, or stakeholder consultation would add strengthen this section.\n\nConclusion: The conclusion can be strengthened- How your findings contribute to your overarching goals?\nTo create a stronger conclusion, consider adding a call-to-action directed at policymakers.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": [
{
"c_id": "12776",
"date": "18 Nov 2024",
"name": "Shalini Bassi",
"role": "Author Response",
"response": "Response Document- Methods: Was this scoping review registered anywhere (e.g., PROSPERO)? Response: Thank you for your insightful comment regarding the registration of our scoping review. In our case, the scoping review was not been registered anywhere, since our research was primarily exploratory and unlike systematic review did not assess the impact of any intervention, we did not feel the need for registration. Secondly, by the time we considered registering, we had already made significant progress in terms of defining the research question and developing the protocol. However, we acknowledge that registering a scoping review is a valuable step to increase transparency and avoid duplication of efforts and will definitely be considered henceforth. The eligibility criteria for inclusion need further clarification. How were the articles screened, and who was responsible for the screening process? This should be clearly outlined to ensure transparency. Response: Thank you for your question. We have elaborated the search strategy as per your suggestion. The polices were screened based on eligibility criteria which have been clearly re-defined. Two researchers (NT, DB) conducted the screening process and any discrepancies were resolved through discussion or consultation with a third researcher (SB) to ensure consistency and minimize bias. All have been included in the strategy. The methodology could benefit from clarification on how comprehensiveness was ensured. Researchers started with 49 and narrowed to 7 policies. Were there any search terms or Boolean logic used? Did the researchers consult any experts to validate that all relevant ministries and policies were included? Response- Thank you for your question. We have edited the search strategy, to provide a more detailed account of the process, for improved clarity as per your suggestion. In addition, we consulted domain experts to ensure that all pertinent ministries and policies were considered to validate the comprehensiveness of our search. The decision to exclude policies focused on micronutrient deficiencies and wasting/stunting could be elaborated upon, given the connection between malnutrition and obesity. A more detailed rationale for exclusion would strengthen this section. Also, clarifying whether this exclusion was based on a theoretical framework, or stakeholder consultation would add strengthen this section. Response: Thank you for your suggestions. The decision to exclude policies was based on the specific focus of the review which was on overweight and obesity. While malnutrition in all forms is interconnected, the causes, interventions and policies for undernutrition (including micronutrient deficiencies and wasting/stunting) differ significantly from those targeting obesity. Hence, as per our understanding, the inclusion of these would have diluted the reviews focus. Additionally, this decision was also supported by domain experts. We have added this to the manuscript as well Conclusion: The conclusion can be strengthened- How your findings contribute to your overarching goals? Response- Thank you! We have revised the conclusion based on your suggestion."
}
]
}
] | 1
|
https://f1000research.com/articles/13-496
|
https://f1000research.com/articles/12-1140/v1
|
12 Sep 23
|
{
"type": "Research Article",
"title": "Hybrid recommender system model for digital library from multiple online publishers",
"authors": [
"Pijitra Jomsri",
"Dulyawit Prangchumpol",
"Kittiya Poonsilp",
"Thammarat Panityakul",
"Dulyawit Prangchumpol",
"Kittiya Poonsilp",
"Thammarat Panityakul"
],
"abstract": "Background: The demand for online education promotion platforms has increased. In addition, the digital library system is one of the many systems that support teaching and learning. However, most digital library systems store books in the form of libraries that were developed or purchased exclusively by the library, without connecting data with different agencies in the same system. Methods: A hybrid recommender system model for digital libraries, developed from multiple online publishers, has created a prototype digital library system that connects various important knowledge sources from multiple digital libraries and online publishers to create an index and recommend e-books. The developed system utilizes an API-based linking process to connect various important sources of knowledge from multiple data sources such as e-books on education from educational institutions, e-books from government agencies, and e-books from religious organizations are stored separately. Then, a hybrid recommender system suitable for users was developed using Collaborative Filtering (CF) model together with Content-Based Filtering. This research purposed the hybrid recommender system model, which took into account the factors of book category, reading habits of users, and sources of information. The evaluation of the experiments involved soliciting feedback from system users and comparing the results with conventional recommendation methods. Results: A comparison of NDCG scores was conducted for Hybrid Score 50:50, Hybrid Score 20:80, Hybrid Score 80:20, CF-score and CB-score. The experimental result was found that the Hybrid Score 80:20 method had the highest average NDCG score. Conclusions: Using a hybrid recommender system model that combines 80% Collaborative Filtering and 20% Content-Based Filtering can improve the recommender method, leading to better referral efficiency and greater overall efficiency compared to traditional approaches.",
"keywords": [
"Recommender systems",
"digital library",
"multiple database",
"user profile",
"hybrid recommender systems",
"collaborative filtering",
"content-based filtering"
],
"content": "1. Introduction\n\nReading is important for human development in terms of education, career development, quality of life, and national development. In Bangkok, Thailand, there are areas for self-learning through books, or public libraries, available free of charge. Libraries are necessary for people at all levels to use their knowledge from books to improve themselves, enhance their quality of life, create equality, and promote reading to the public. In addition, data published by the World Bank, UNESCO, and the United Nations (UN) demographic data indicate that the Covid-19 outbreak has contributed to over 17% of children worldwide facing a learning crisis. This may affect the potential of the modern population. Also, schools around the world have had to close more than usual over the past year. School closures have resulted in students having to switch to online classes, but the learning system does not cover the world, and many children do not have access to technology to study online,1,2 which may result in a lack of basic literacy skills.\n\nCurrently, technology and telecommunication play an essential role in human life, coupled with rapidly advancing computer technology and communication systems. Therefore, the digital library system is another channel for collecting information or electronic books from multiple sources and disseminating them through the Internet. This allows children and general readers to access and search for books through a computer network without any restrictions on location, distance, and duration. It is an opportunity to expand the results of learning resources from physical to online, without borders, to expand opportunities and increase access to books, media, and publications, promoting reading widely and in line with modern society. However, the current online library system is not user-friendly because e-books are stored scattered in separate databases developed by each agency. In addition, most government economic development plans push for the promotion of reading and learning through modern regional library services, creating opportunities for youth groups to have access to quality services that are convenient and fast.\n\nBased on such problems, the researcher has developed a digital library model by studying techniques for combining multiple E-book database systems and using content to create an index from multiple structures to serve users in the Bangkok area. Books were gathered from many important sources, and this system was able to enable the public to access the library system in an online format by designing a database system that linked electronic books from multiple databases together, collecting book information from many sources such as the National Library, government agencies, teaching materials, Dhamma books, novels, and short stories. Moreover, this research presents a model for recommending electronic books to users using the hybrid recommender systems model, combining Collaborative Filtering (CF), heuristic Content-based filtering, and user’s personal data. The collaborative filtering of this research concentrates on user reading, while Content-based filtering concentrates on titles, authors, book categories, keywords, and book details to offer suggestions to users in the area of their interest.\n\nThe structure of this paper is as follows: Section 2 provides a background and relevant literature. Section 3 outlines the methodology and framework employed in the hybrid recommender system. Section 4 shows the experimental outcomes. Lastly, Section 5 concludes the research and offers recommendations for future research.\n\n\n2. Literature review\n\nRecommender systems are ubiquitous on the internet. Typically, news websites feature a banner that displays recommendations such as “You may also like” or “People who liked this article also enjoyed this one.” This approach aligns with the traditional definition of recommender systems as outlined by Resnick and Varian,3 that they are systems that study a user's preferences for a given object to make suggestions that might be useful to the user. Recommender systems enable users to customize their profiles, receive tailored suggestions, and make informed decisions about products and services that align with their preferences. The five primary recommendation techniques include: collaborative filtering, content filtering, demographic filtering, knowledge-based filtering, and utility-based filtering.4 A more fundamental way of categorizing recommender systems is to divide techniques into three primary groups: collaborative filtering, content-based filtering, and hybrid approaches.5\n\n• Content-based filtering utilizes the \"Content\" feature of an item to generate user profiles based on their preferences and selections. This technique suggests a list of items that are similar to those that a user has already viewed or appreciated.6–8\n\n• Collaborative filtering relies on the exchange of opinions and feedback among users. This technique suggests a list of items that have been favored by other users with similar preferences.9–11\n\n• The Hybrid Approach is a blend of Content-based and Collaborative Filtering that leverages both user preferences and item attributes. This technique utilizes a matrix derived from filtering interactions and contextual data from Content-based filtering to provide personalized recommendations.12–14\n\nIn general, most databases are stored separately for different service providers. Users must know the source and explore various topics of interest.15–22 However, some researchers have concluded that a single database is not sufficient to retrieve knowledge for users. Several referral systems for digital libraries have been proposed. Many researchers apply a hybrid model to improve recommender systems. Porcel et al. propose a hybrid system by combines collaborative recommendations and content-based.23 Tejeda-Lorente et al. present a quality-based recommender system that considers the quality of an item in order to assess its relevance.24 Serrano-Guerrero et al. present a fuzzy linguistic recommender model in a university digital library. This model uses the Google Wave approach that provides a shared space for different users and resources.25 Morawski et al. offer a hybrid recommender system for rural libraries by combining content-based and collaborative filtering. The authors suggest the concept of a fuzzy flavor vector to deal with the problem of \"cold start\" problems caused by the smaller size of this library and the usual sparse data sets.26 Jomsri proposes a library book recommendation system based on user profiling and association rules.27 Some researchers focus a patron-driven hybrid library recommender system by applying machine learning techniques to recommend weeding decision-making operations by extracting and analyzing users' opinions and ratings.28\n\nSome researchers have tried to develop models for library services, such as Yang and Hung's proposed recommender system for book acquisition in libraries. The authors employ a basic metric that does not consider user feedback or opinions.29 Wu et al. have introduced a library book acquisition recommender system that employs a network ranking mechanism.30 Cabrerizo et al. suggest an extension to the LibQUAL+ model to address users' perceptions and evaluate the quality of library services.31–32 Some researchers use linked information spaces for different scientific digital libraries in Digital Humanities.33 Another researcher conducted a study with the aim of developing a recommendation system model that integrates various types of supplementary information, apart from explicit ratings assigned to items. This supplementary information includes social connections between users and data on the items being recommended.34 The main aim of researching the Hybrid Recommendation model is to overcome the issue of insufficient rating data by integrating the information from Content-Based and Collaborative Filtering models. Numerous studies have been conducted in this area, including one that implemented the Bayesian Probabilistic Matrix Factorization Framework to tackle the sparsity problem by supplementing taste data with user evaluation data stored in a matrix. Another study utilized an auto-encoder to learn side information data when user preference information is inadequate. Furthermore, a study was carried out to integrate information by utilizing an automatic encoder to learn the nonlinear activity of users and items while removing stacked noise.35,36 The technique for recommender in this paper applies a hybrid approach model and creates an API for connecting content from multiple E-book databases to recommend users.\n\n\n3. Methodology and framework of hybrid recommender system\n\nThis part describes the framework of hybrid recommender system including API function for connect multiply publisher, architecture of the book recommendation system, hybrid recommender systems model. The concept of hybrid recommender system was shown in Figure 1. This is a functional overview of a hybrid recommender system for a digital library from multiple online publishers. The system collects data from various publishers by creating a retrieval API and gathers important metadata for indexing. The metadata of various e-books are stored in the database of the developed system, without storing the ebook file from the publisher to maintain the book's copyright. Partnered publishers for this edition of the book collection include the Listing Agency, Arsom Silp Institute of the Arts, and The Secretariat of the House of Representatives, all of which are valuable books in Thailand. The next step is to develop a digital library system with a channel for accessing book information. The login will be in the form of a one-time login for users to access all book listings linked to the system. The final step is to develop a recommendation system in the form of a hybrid recommender system and present the recommendation results to the user.\n\nThe process of collect Mata data from other sources. The system will link the book information through the database of the service provider and crawl data to collect information on each book for a created index such as title, category details, URL, etc. Therefore, users can read the original E-book through the URL of the book provider directly to support copyright from each E-book database policy. This prototype had a wide variety of e-books from a different database of organizations. All organizations encouraged Thai people to have access to reading services research information free of charge by creating functions to connect E-book data. However, the function may be adjusted according to the connection characteristics of different database systems. Initially, the system pass parameters required by the service and return values for data use as the following API functions including:\n\n• Login function: The Login function supports user login and user logout.\n\n• Get books list function: This function retrieves a list of all books purchased by the agency, along with basic information such as the title, author, publisher, number of pages, and number of copies.\n\n• Get Category function: This function retrieves a list of book categories that the agency purchases, along with the number of books in each category.\n\n• Get books by category function: This function retrieves a list of books in a specific category, along with basic information such as the title, author, publisher, number of pages, and number of copies.\n\n• Get book type function: This function retrieves a list of book types that the agency purchases, along with the number of books of each type.\n\n• Get books by book type function: This function retrieves a list of books in a specific book type, along with basic information such as the title, author, publisher, number of pages, and number of copies.\n\n• Get book detail function: This function retrieves detailed information about a specific book, such as the title, author name, publisher, ISBN, year of publication, number of pages, number of volumes, and description.\n\n• Search books function: This function searches for books available in the system based on the search query, which can be by title, author, publisher, or description.\n\n• Read book function: This function checks the number of books that can be opened for reading.\n\n• Checkout function: This function checks the number of books that can be checked out for online borrowing.\n\nThe architecture for developing the book recommendation system in the digital library consists of several steps, which are illustrated in Figure 2:\n\n• Crawler Data is a detail within the session that connects multiple publishers. The research develops programs responsible for extracting data from online databases and storing it in a database. The system collects the following information: title, author, date, month, year of publication, and ISSN, which is useful for monitoring user interest and indexing each e-book.\n\n• Digital Library corpus is a database used to store details of books that Crawler retrieves from an authorized database system and is an e-book database system developed by the library itself.\n\n• User Profile is created by storing information about each user's reading behaviour, such as books they have read, books they have selected for their shelf, and books they have rated or reviewed, and these data are then processed to find out which books and what categories the user likes or dislikes in order to bring information to be fed to the Recommender System to recommend other books that are similar in content or genre to the books the user has already read and enjoyed. The system can also suggest books based on the user's reading history and preferences, such as authors or topics they have shown interest in.\n\n• Hybrid recommender system Combines the recommendations from Content-Based Filtering and Collaborative Filtering to generate a final list of personalized book recommendations for the user. The details are described in the next Session.\n\nUser Profiles can be stored and collected in the form of implicit feedback, including which books users view details and place on their personal bookshelves. Creating user profiles is a process of building a model of user settings. Assuming that there are n users participating in the system, m is books have been read, o is books have been keep in user shelf, and p is books have been reviewed.\n\nLet U be a set of all the users contained in the system; U = {U1, U2 …, Un}, R is a set of books read from digital library collection; R = {r1, r2 •••, rm}, K is a set of keep from digital library collection; K = {k1, k2 •••, ko}, V is a set of rating; V = {v1, v2 •••, vp}, URKVijal is a set of user read books and keep book and rating book by user Ui; URKVijkl = {urkvilal, urkvi2al, …, urkvijal} and Let E (ui, urkvijal) indicates a relationship among user Ui, with read URij. Here is the definition of the user profile.:\n\nDefinition [User Profile]:\n\nFor a user pi where i = 1, .., n;\n\nLet Ui; be a user profile of user ui.\n\nUi; = {< ui, urkvijal>/urkvijal∈URKV^ ui∈U ^ E (ui, urkvijal) = 1}\n\nWhen a new user signs up for the digital library system, the recommender system may not be able to generate accurate recommendations since there haven't been any interactions between the user and the books. Additionally, if the model hasn't been updated since the user's registration, the system may not recognize their existence and thus cannot make any predictions for them through CF. To resolve these problems, during the registration process, users are required to select one to three preferred categories. This information is used by a customized content-based filtering algorithm to provide personalized recommendations until the CF model can generate high-quality recommendations based on the user's interactions.\n\nA hybrid recommender system is a process that introduces e-books by analyzing data from users' reading behavior. The system utilizes a combination of Collaborative Filtering (CF) and Content-Based Filtering (CB) to recommend e-books to users. This involves applying a weighted score to the recommendations generated by each of these methods. The process of hybrid recommending e-books to individual users is designed to suggest related e-books or e-books that users are expected to like. This is done by considering the User Profile that is collected from the user. The User Profile includes a set of user read books, the books that are kept in the shelf, and ratings given by the user to different books.\n\n• Collaborative Filtering is used to identify users who have similar preferences and interests based on their reading behavior. This involves analyzing the behavior of similar users to identify e-books that the user might be interested in. The User Profile is used to identify similar users who share similar interests and preferences. This method is effective in generating recommendations for users who have similar reading habits. The maximum score of user similarity is one.\n\n• Content-Based Filtering, on the other hand, recommends e-books based on the factors that the user has liked in the past. This involves analyzing factors such as the category of books, the publisher, and the year of publication. This method is useful for recommending e-books that match the user's specific preferences. All of three factors are combined and maximum score is one.\n\nTo generate a final list of personalized e-book recommendations for the user, the recommendations generated by both Content-Based Filtering and Collaborative Filtering are combined. The system uses a weighting scheme to determine the relevance of each recommendation, based on factors such as the user's past behavior, the popularity of the e-book, and other relevant factors. This results in a list of e-books that are tailored to the user's interests and preferences, increasing the likelihood that the user will find e-books that they enjoy reading. Here is a formula for a hybrid recommender system that merges collaborative filtering and content-based filtering techniques:\n\nSuch as:\n\nCF Score = similarity between the target user and other users who have similar preferences\n\nCB Score = relevance score of recommended items based on their content\n\nα = a weighting factor that determines the relative importance of the two scores\n\n\n4. Experimental approach\n\nThe environment in which the experiment is conducted is split into three distinct parts. The first section describes the data set, the second describes the evaluation metric, and the last section describes the experimental results.\n\nThe collection of E-books comprises 2,715 items, while the number of members registered is 370 members from Library System for Learning in 2022. The digital library dataset includes the following information for each item: book ID, title, description, keywords, book categories, keywords, and book details, category of books, the publisher, and the year of publication, and either an e-book file in the owner's system or a URL for accessing the full E-book in the case of books from partners.\n\nIn the experimental setup, the research participants were assigned the task of exploring books from the digital library. The thirty subjects who were interested in reading digital books and were proficient in using applications were invited for evaluation. Each participant was given six different search queries, and all queries were tested using different ranking approaches. The search engines presented the top 15 documents according to their relevance, with i representing the ranking number {i = 1, 2, 3, …, 15}. The participants were then asked to rate the relevancy of the search results using a five-point scale: Score 0 indicating \"not relevant at all,\" Score 1 indicating \"probably not relevant,\" Score 2 indicating \"less relevant,\" Score 3 indicating \"probably relevant,\" and Score 4 indicating \"extremely relevant.\"This paper utilized the Normalized Discounted Cumulative Gain (NDCG) metric to measure the performance of every search engine.37 This measurement is specifically designed for evaluating web search performance. The NDCG was calculated using the equation (2).\n\nThe parameter k represents the truncation or threshold level, while the integer r(j) denotes the relevancy score given by the research participant. The normalization constant Mq is calculated to ensure that the ideal ordering would achieve an NDCG score of 1. The NDCG metric emphasizes relevant documents that appear among the top search results while penalizing irrelevant documents by reducing their impact on the NDCG score.\n\nUser evaluation refers to the process of collecting feedback from users on the performance of a recommender system. NDCG average score is a metric used to evaluate the performance of the system, calculated by taking the average of the NDCG scores for all users in the dataset. A comparison of NDCG of Hybrid Score50:50, Hybrid Score20:80, Hybrid Score80:20, CF-score and CB-score are shown in Figure 4. CF-score and CB-score are standalone recommendation algorithms that use either CF or CB exclusively. The study compares the average NDCG scores of five distinct recommender approaches. The graph has the x-axis representing the top 15 ranks of the search results and the y-axis displaying the NDCG score. Based on the graph, it appears that the Hybrid Score80:20 method has the highest NDCG average score among the five different recommender approaches being compared. This suggests that the Hybrid Score80:20 algorithm is the most effective at recommending relevant items to users.\n\nThis research applied One Way ANOVA on NDCG at top fifteen ranks (K = 1, 1-2, 1-3,…, 1-15) respectively to test whether there is a difference among the mean NDCG from three different recommender system model approaches. The result indicates that the means of NDCG for the tree approaches to recommender system models were not equal with a significance level of α = 0.05. In simpler terms, there was a statistically significant difference in the search results.\n\n\n5. Conclusion\n\nThe main focus of this research paper is the utilization of a heuristic recommender system that utilizes a Hybrid model. Thirty participants were involved in the study, and each participant generated six queries to investigate the e-books obtained through the recommender system. The top 15 documents for each search engine were displayed for relevance, and the participants rated the search results on a five-point scale based on relevancy. The results of the study indicate that the Hybrid model outperforms other models with a higher NDCG score, which suggests that the Hybrid Score80:20 performs better than other recommender models. Additionally, a One Way ANOVA was used to further analyze the mean difference results of CF-score and CB-score. The statistical testing results indicate that the mean NDCG scores differ among the Hybrid model, CF-score, and CB-score at k = 1-15. However, the mean NDCG scores do not differ between the Hybrid model and CF-filtering. The study suggests that further experimentation should be conducted to explore different Hybrid models. In the future, research in this area should also extend personalization with deep learning methods. The paper has some limitations such as the sample size of 30 participants, which may not be representative of the wider population, and may limit the generalizability of the study findings. Additionally, the participants in the study may have had different levels of familiarity with the e-books, which could have influenced their ratings of relevancy. Moreover, the study highlights the importance of using a hybrid model to improve the effectiveness of recommender systems. In future work, it is recommended to investigate the potential of deep learning methods to enhance the personalization of the hybrid model.",
"appendix": "Data availability\n\nThis research cannot provide the underlying data because it involves copyrighted data from multiple publishers, and all publishers have agreements that prohibit developers from disseminating book information and user experimentation data under the principles of the Personal Data Protection Act (PDPA). The data set was sourced from the Bangkok Digital Library System at https://www.bangkoklibrary.go.th/digital/. To access the dataset, please contact us via email at addigitallibrarybkk@gmail.com.\n\nFigshare: Evaluation form for Subject Test.pdf. https://doi.org/10.6084/m9.figshare.22308823.v1\n\nThis project contains the following extended data:\n\n- Evaluation form for Subject Test.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nLi Y, Nishimura N, Yagam H, et al.: An Empirical Study on Online Learners’ Continuance Intentions in China. Sustainability. 2021; 13: 889. 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PubMed Abstract | Publisher Full Text\n\nAhmadi M, Ershad-Sarabi R, Jamshidiorak R, et al.: Comparison of bibliographic databases in retrieving information on telemedicine. J. Kerman Univ. Med. Sci. 2014; 21: 343–354.\n\nLorenzetti DL, Topfer L-A, Dennett L, et al.: Value of databases other than MEDLINE for rapid health technology assessments. Int. J. Technol. Assess. Health Care. 2014; 30: 173–178. PubMed Abstract | Publisher Full Text\n\nBeckles Z, Glover S, Ashe J, et al.: Searching CINAHL did not add value to clinical questions posed in NICE guidelines. J. Clin. Epidemiol. 2013; 66: 1051–1057. Publisher Full Text\n\nHartling L, Featherstone R, Nuspl M, et al.: The contribution of databases to the results of systematic reviews: a crosssectional study. BMC Med. Res. Methodol. 2016; 16: 1–13.\n\nAagaard T, Lund H, Juhl C: Optimizing literature search in systematic reviews—are MEDLINE, EMBASE and CENTRAL enough for identifying effect studies within the area of musculoskeletal disorders? BMC Med. Res. Methodol. 2016; 16: 161. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPorcel C, Moreno JM, Herrera-Viedma E: A multi-disciplinar recommender system to advice research resources in university digital libraries. Expert Syst. Appl. 2009; 36(10): 12520–12528. Publisher Full Text\n\nTejeda-Lorente Á, Porcel C, PeisE SR, et al.: qualitybased recommender system to disseminate information in a university digital library. Inf. Sci. 2014; 261: 52–69. Publisher Full Text\n\nSerrano-Guerrero J, Herrera-Viedma E, Olivas JA, et al.: A google wave-based fuzzy recommender system to disseminate information in university digital libraries 2.0. Inf. Sci. 2011; 181(9): 1503–1516. Publisher Full Text\n\nMorawski J, Stepan T, Dick S, et al.: A fuzzy recommender system for public library catalogs. Int. J. Intell. Syst. 2017; 32(10), 1062–1084. Publisher Full Text\n\nJomsri P: Book recommendation system for digital library based on user profiles by using association rule. 2014 Fourth International Conference on Innovative Computing Technology (INTECH). IEEE; 2014; pp. 130–134.\n\nRhanoui M, Mikram M, Yousfi S, et al.: A hybrid recommender system for patron driven library acquisition and weeding. J. King Saud Univ.-Comput. Inf. Sci. 2020.\n\nYang S-T, Hung M-CA: model for book inquiry history analysis and bookacquisition recommendation of libraries. Libr. Collect. Acquis. Tech. Serv. 2012; 36(3–4): 127–142. Publisher Full Text\n\nWu F, Hu Y-H, Wang P-R: Developing a novel recommender network-based ranking mechanism for library book acquisition. Electron. Libr. 2017; 35(1): 50–68. Publisher Full Text\n\nCabrerizo FJ, Morente-Molinera JA, Pérez IJ, et al.: A decision support system to develop a quality management in academic digital libraries. Inf. Sci. 2015; 323: 48–58. Publisher Full Text\n\nCabrerizo FJ, López-Gijón J, Martínez M, et al.: A fuzzy linguistic extended libqual+ model to assess service quality in academic libraries. Int. J. Inf. Technol. Decis. Mak. 2017; 16(01): 225–244. Publisher Full Text\n\nBartalesi V, Pratelli N, Lenzi E: Linking different scientific digital libraries in Digital Humanities: the IMAGO case study. Int. J. Digit. Libr. 2022; 23: 303–317. Publisher Full Text\n\nZhao H, Yao Q, Song Y, et al.: Side Information Fusion for Recommender Systems over Heterogeneous Information Network. ACM Trans. Knowl. Discov. Data. 2021; 15: 1–32. Publisher Full Text\n\nKim YM, Choi S: Scalable Variational Bayesian Matrix Factorization with Side Information. Proceedings of the Seventeenth International Conference on Artificial Intelligence and Statistics, Reykjavik, Iceland. 22–25 April 2014; pp. 493–502.\n\nStrub F, Gaudel R, Mary J: Hybrid Recommender System Based on Autoencoders. Proceedings of the 1st Workshop on Deep Learning for Recommender Systems, Boston, MA, USA. 2016; pp. 11–16.\n\nKekäläinen J, Järvelin K: Evaluating information retrieval systems under the challenges of interaction and multidimensional dynamic relevance. Proceedings of the 4th CoLIS conference. 2002; pp. 253–270"
}
|
[
{
"id": "216613",
"date": "10 Nov 2023",
"name": "Asefeh Asemi",
"expertise": [
"Reviewer Expertise Library and Information Science",
"Recommender Systems"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nClarity and Accuracy: The text is well-organized and provides a clear structure for the research paper. The abstract, introduction, methodology, and results sections are clearly defined.\n\nStudy Design and Technical Soundness: The study design seems appropriate for the research question of developing a hybrid recommender system for a digital library. The technical components, such as the API connection and hybrid recommender system model, are well-described.\nDetails of Methods and Analysis: The methods section provides an overview of the digital library corpus, evaluation metric (NDCG), and experimental results. However, specific details about the algorithms used in Collaborative Filtering (CF) and Content-Based Filtering (CB) are not provided. More information on these aspects would enhance the clarity.\nStatistical Analysis: The use of the Normalized Discounted Cumulative Gain (NDCG) as an evaluation metric is appropriate for assessing the performance of the recommender system. The statistical analysis, particularly the One Way ANOVA, adds a quantitative aspect to the evaluation.\nSource Data Availability: The authors mention that the underlying data cannot be provided due to copyright restrictions from multiple publishers. However, they offer a link to the Bangkok Digital Library System for accessing the dataset.\nSupport for Conclusions: The conclusion suggests that the Hybrid Score 80:20 method outperforms other models. The provided graph supports this claim.\nConstructive Feedback: To enhance clarity, provide more details about the algorithms used in Collaborative Filtering (CF) and Content-Based Filtering (CB). Consider expanding on the limitations of the study, especially regarding the small sample size of 30 participants and potential biases in their familiarity with e-books. Encourage the authors to provide more context on the specific challenges faced in connecting data from multiple online publishers and how these challenges were addressed in the development of the hybrid recommender system.\nThe work appears promising, but additional details, especially regarding the specific algorithms used, and further context on challenges faced during implementation would contribute to a more comprehensive understanding of the research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "11825",
"date": "18 Nov 2024",
"name": "pijitra jomsri",
"role": "Author Response",
"response": "Thank you for your valuable guidance on improving my paper. I am pleased to inform you that I have revised the paper (Version 2) according to your recommendations. The following improvements have been made such as: 1. Increased Sample Size: The sample size has been increased to 75 participants to expand the dataset and provide additional comparative results. The experimental findings, as shown in Table 2, indicate that the Hybrid Score 80:20 still performs better. 2. Enhanced Algorithm Details: Additional details about the algorithms have been provided in Section 3.1 (Function for Connecting Multiple Publishers) and Section 3.3 (Hybrid Recommender Systems Model) to clarify the methodology. 3. Challenges and Solutions: Additional information regarding the challenges faced in connecting data from multiple online publishers has been included in the Conclusion."
}
]
},
{
"id": "222585",
"date": "30 Nov 2023",
"name": "Muhammad Yousuf Ali",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI appreciated the Authors research work about the recommender system. However, following the following points are recommend to improve the readership and audience of this article.\n\n1. Research objective is the one of the key point to carry out/conduct any research but authors did not mentioned research objective. Recommend add this research objective.\n2. In this research paper researcher(s) did not mention what the research questions are and they try to explore the answer to the Research questions or hypothesis they are trying to test.\n\n2.The Methodology section is missing the basic concept of the research. The authors try to carry out Quasi Experimental designed research, but did not express this methodology and not include any citations.\n\n3. N=30, as the authors mentioned in section 5.0 line 1, did not define the population/sample characteristics. Define the sample like students, researchers, general public, children or women take part in this study.\n\n4. \"Experimental Results\" Section 4.3, the authors applied a One way ANOVA test. I will recommend to draw a non-directional hypothesis that: \"Is there any significant relationship between the Content filtering (CF) score and Content base (CB) score\", and you validate your hypothesis accordingly.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "11826",
"date": "18 Nov 2024",
"name": "pijitra jomsri",
"role": "Author Response",
"response": "I am deeply grateful for your valuable guidance on improving my paper. I am pleased to inform you that I have revised the paper (Version 2) according to all your recommendations. Here are the details of the revisions as follow: 1.Objective of Paper: Added the objective, \"To develop a digital library model by studying techniques for combining multiple e-book database systems,\" which now appears in Section 1. Introduction. 2.Research Questions: Added the research question, \"The researcher believes that a hybrid recommender system model can enhance the efficiency of book recommendations in the digital library system,\" also in Section 1. Introduction. 3. Methodology : Expressed detailed methodology and added citations in Section 4.2 Evaluation Metric. 4. Sample Characteristics: Defined the characteristics of the sample and increased the sample size from 30 to 75 participants, as specified in Section 4.2 Evaluation Metric. 5. Hypothesis: In Section 4.3, I have formulated the hypothesis as recommended by the reviewer."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1140
|
https://f1000research.com/articles/11-754/v1
|
06 Jul 22
|
{
"type": "Systematic Review",
"title": "Single-incision laparoscopic cholecystectomy versus conventional multi-port laparoscopic cholecystectomy: A systematic review, meta-analysis, and meta-regression of randomized controlled trials",
"authors": [
"Reno Rudiman",
"Ricarhdo Valentino Hanafi",
"Alma Wijaya",
"Ricarhdo Valentino Hanafi",
"Alma Wijaya"
],
"abstract": "Background: Conventional multi-port laparoscopic cholecystectomy (CMLC) has become the current ‘gold standard’ technique in gallbladder disease. Single-incision laparoscopic cholecystectomy (SILC) has gained attention due to its benefits in improving patient cosmetic results and pain reduction. We aim to assess the latest evidence on the feasibility, safety and surgical outcomes of SILC and CMLC. Methods: We conducted searches for randomized controlled trials (RCTs) in PubMed, PubMed Central (PMC), and Europe PMC between December 2011 and 2021. The latest search was conducted in January 2022. We analyzed several outcomes, including perioperative complications, estimated blood loss, operation time, conversion to open surgery, hospital stay, pain score, cosmesis, and days of return to work. Cochrane Risk of Bias (RoB) 2.0 tool was used to evaluate quality of studies. Mantel-Haenszel's formula and Inverse Variance method were conducted to synthesize results. This study was accomplished in accordance with the PRISMA guidelines. Results: A total of 37 studies were eligible, with a total of 2,129 and 2,392 patients who underwent SILC and CMLC. Our study demonstrated a superiority of SILC for the visual analog score (VAS) at six hours post-operation [mean difference (MD) -0.58 (95% CI -1.11, -0.05), p=0.03], cosmesis one-month post-operation [standard MD 2.12 (95% CI 1.10, 3.13), p<0.0001], and cosmesis six months post-operation [standard MD 0.53 (95% CI 0.06, 0.99), p<0.0001]. Meanwhile, SILC showed a longer operation time [MD 10.45 (95% CI 6.74, 14.17), p<0.00001]. In terms of VAS at four time points (4, 8, 12, and 24 hours), perioperative complications, estimated blood loss, conversion to open surgery, hospital stay and days to return to work, SILC did not differ from CMLC. Conclusions: SILC is a safe, feasible and favorable procedure in terms of pain reduction and cosmetic results. The option between both procedures is based on surgeon preferences. Registration: PROSPERO (CRD42022306532; 23 February 2022).",
"keywords": [
"Cholecystectomy",
"laparoscopic surgery",
"meta-analysis",
"minimal invasive surgery",
"systematic review"
],
"content": "Introduction\n\nFor decades, conventional multi-port laparoscopic cholecystectomy (CMLC) has been a favored procedure in gall bladder diseases.1 This technique differs from any laparoscopic surgery, which requires advanced technology and skill. The gains in CMLC aggregate the learning curve and surgical aftermaths.2 Many adjustments and modifications are made in CMLC; fundamentally, CMLC consists of four ports. The adaptations may be a reduced port size, such as 10 mm to 5 mm or 5 mm to 2/3 mm, or reduced port numbers. These changes intend to amend patient outcomes in any aspect.3\n\nThe curiosity about single-incision laparoscopic cholecystectomy (SILC) has increased in the past years. A single incision implies when many ports are inserted at a single site (umbilicus). Many studies have demonstrated technical difficulty and increasing complications.4,5 A recent study indicated a feasible and valuable technique with superior cosmetic outcomes, pain reduction, and nil complications.6 We speculate that knowledge about SILC will improve in the following years.\n\nPros and cons remain disputable in many systematic reviews.7–12 We would like to update the recent randomized controlled trials (RCTs) regarding these techniques because there has not been a newer systematic review to analyze the latest amendment. The latest meta-analysis by Lyu et al.,12 determined that a limitation of their study was that only three and four ports of instruments, plus non-RCT were included; thus, our study addresses the limitations of the latest research and expects different outcomes. Our hypothesis is that SILC is superior to CMLC in all aspects. Consequently, this study aimed to assess and evaluate the latest evidence on the feasibility, safety, and surgical outcomes of SILC and CMLC.\n\n\nMethods\n\nWe conducted a systematic review and meta-analysis study from clinical trial studies. We registered this systematic review in PROSPERO (CRD42022306532) on 23 February 2022. Articles were included in this systematic review and meta-analysis if they fulfilled the Population, Intervention, Comparison, Outcomes and Study (PICOS) framework as follows:\n\n• P - Population: Adults aged >18 years old with body mass index (BMI) <35 kg/m2 with uncomplicated gall bladder disease who were eligible to undergo either SILC or CMLC with the American Society of Anesthesiology (ASA) Score I-III.13\n\n• I - Intervention: Patients who underwent SILC to treat their gall bladder diseases.\n\n• C - Comparator: Patients who underwent CMLC as surgical treatment for gall bladder diseases.\n\n• O - Outcomes: Bile duct injury (BDI), bile leakage, gallbladder perforation, wound infection, incisional hernia, total intraoperative complications, total post-operative complications, conversion to open cholecystectomy, operating time, estimated blood loss volume, length of hospital stay, cosmesis (satisfactory quantitative scores) at one month and six months post-operation, days to return to work, and post-operative pain score assessed by a visual analog score (VAS) at five-time points (4, 6, 8, 12, and 24 hours post-procedure).\n\n• S - Study design: Randomized clinical trials\n\nAll studies besides original articles (correspondence, letter to editor, or review articles), observational studies (cohort or case-control designs), case series, case report studies, studies reported in a language other than English, research focusing on pregnant women and populations below the age of 18 years were excluded.\n\nWe conducted systematic literature searches in three databases: PubMed (RRID:SCR_004846), PubMed Central (PMC) (RRID:SCR_004166), and Europe PubMed Central (EuroPMC) (RRID:SCR_005901) from December 2011 until December 2021. The latest search was conducted in January 2022. To filter the intended studies, combined keywords were used, but were not limited to, the following: “single-incision”, “single-port”, “single access”, “conventional”, “standard”, “multi-port”, “laparoscopic cholecystectomy”. Two researchers (RR and RVH) independently screened the titles and abstracts to find the eligible articles. Additional evaluation of references from eligible studies was also conducted to search for more potential articles. Full-text articles were then assessed independently according to the inclusion and exclusion criteria. This study is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines63 and the PRISMA diagram shows the strategy we employed during our study (Figure 1).\n\nRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; EuroPMC, Europe PubMed Central; RCT, randomised controlled trial.\n\nTwo researchers (RR and RVH) independently conducted the data extraction process. An extraction form was developed to list information about the study, such as the study’s general information (title, authors, year of publication, study design), population characteristics, and outcomes measured. The data were then extracted through Covidence (RRID:SCR_016484). Conflicts in data abstraction were resolved by consensus and referring to the original article.\n\nTwo authors (RR and RVH) assessed the quality of each study involved in this review independently. The Cochrane Risk of Bias (RoB) 2.0 tool was used to evaluate the quality of clinical trial studies. This tool is comprised of five domains, including (1) bias arising from the randomization process; (2) bias due to deviations from intended interventions; (3) bias due to missing outcome data; (4) bias in measurement of the outcome; and (5) bias in the selection of the reported results. The final judgments of each domain were categorized as low risk, some concerns, or high risk. The summarized five domains of RoB were concluded by RR and RVH, whereas a discussion with AW resolved any discrepancies in the judgments to reach the final consensus.\n\nMeta-analysis was done using Review Manager 5.4 (Cochrane Collaboration) and Comprehensive Meta-Analysis version 3 software. The Mantel-Haenszel formula was used to obtain the risk ratio (RR) and 95% confidence interval (CI). At the same time, the Inverse Variance method was used to obtain the mean difference (MD), standardized mean difference (SMD), and standard deviation (SD). We used the random-effects model for all outcomes of interest in this study, regardless of heterogeneity. This meta-analysis assessed heterogeneity between studies by I-squared (I2; inconsistency). The I2 statistic with a value of <25% is considered a low degree of heterogeneity, 26-50% is a moderate degree of heterogeneity, and >50% is considered a high degree of heterogeneity. Funnel plot analysis was utilized to assess the qualitative risk of publication bias, while Egger’s regression method was used to evaluate the quantitative risk of publication bias.\n\n\nResults\n\nThe initial search generated 222 records, in which 37 RCTs were included for qualitative synthesis (systematic review) following the screening, removing duplication, and excluding of several studies (Figure 1).14–50 These final included RCTs yielded 2,129 and 2,392 patients who underwent SILC and CMLC. All patients had uncomplicated gall bladder diseases with ASA grade I-III and were eligible to undergo both techniques. The types of surgical ports ranged from conventional instruments to specific models. Three studies were double-blind RCTs, one was a single-blind RCT, and the remaining RCTs did not elaborate on the blinding method. A total of 10 studies were excluded due to including BMI >35 kg/m2, age <18 years old, and retrospective study.51–60 The full details of data characteristics are available in Table 1.\n\nThe Cochrane RoB 2.0 tool was applied to determine the quality of RCTs. A total of 33 studies were categorized as low risk of bias studies. Two studies were determined to have some concerns because the long-term follow-up results could not be fully concluded. The other two studies were evaluated for having a high risk of bias due to having a higher percentage of loss to follow-up and a high risk of false-positive results. The evaluation of RoB is summarized in Figure 2.\n\nBile duct injury\n\nA total of 17 studies (n=2,114) reported the BDI outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of risk for BDI [RR 0.83 (95% CI 0.17–4.04), p=0.82, I2=0%, random-effect modeling] (Figure 3A).\n\n(A) Bile duct injury. (B) Bile leakage. (C) Gall bladder perforation. (D) Wound infection. SILC, single-incision laparoscopic cholecystectomy; CMLC, conventional multi-port laparoscopic cholecystectomy.\n\nBile leakage\n\nA total of 16 studies (n=2,363) reported on the bile leakage outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of risk for bile leakage incidence [RR 1.31 (95% CI 0.72–2.39), p=0.38, I2=0%, random-effect modelling] (Figure 3B).\n\nGallbladder perforation\n\nNine studies (n=1,874) reported on the gallbladder perforation outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of gallbladder perforation incidence [RR 0.94 (95% CI 0.71–1.26), p=0.68, I2=0%, random-effect modelling] (Figure 3C).\n\nWound infection\n\nA total of 24 studies (n=2,926) reported on the wound infection outcome. Our pooled analysis showed that the SILC procedure did not change the risk of wound infection incidence when compared with the CMLC procedure [RR 1.20 (95% CI 0.72–2.03), p=0.48, I2=0%, random-effect modelling] (Figure 3D).\n\nIncisional hernia\n\nA total of 28 studies (n=3,788) reported on the incisional hernia outcome. Our pooled analysis showed that the SILC procedure did not change the risk of incisional hernia incidence when compared with the CMLC procedure [RR 1.43 (95% CI 0.75–2.74), p=0.28, I2=0%, random-effect modelling] (Figure 4A).\n\n(A) Incisional hernia. (B) Total intra-operative complications. (C) Total post-operative complications. SILC, single-incision laparoscopic cholecystectomy; CMLC, conventional multi-port laparoscopic cholecystectomy.\n\nTotal intra-operative complications\n\nA total of 26 studies (n=3,717) reported on the total intra-operative outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of the incidence of total intra-operative complications [RR 1.22 (95% CI 0.93–1.59), p=0.15, I2=0%, random-effect modelling] (Figure 4B).\n\nTotal post-operative complications\n\nA total of 30 studies (n=3,882) reported on the total post-operative outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of the incidence of total post-operative complications [RR 1.04 (95% CI 0.93–1.59), p=0.15, I2=0%, random-effect modelling] (Figure 4C).\n\nEstimated blood loss\n\nA total of 12 studies (n=1,416) reported on the estimated blood loss outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of estimated blood loss volume [MD 1.29 (95% CI -0.85, 3.43), p=0.24, I2=86%, random-effect modelling] (Figure 5A).\n\n(A) Estimated blood loss. (B) Operation time. (C) Conversion to open surgery. (D) Hospital stay. SILC, single-incision laparoscopic cholecystectomy; CMLC, conventional multi-port laparoscopic cholecystectomy.\n\nOperation time\n\nA total of 34 studies (n=3,972) reported on the operation time outcome. Our pooled analysis showed that the SILC procedure significantly increased the length of operation time when compared with the CMLC procedure [MD 10.45 (95% CI 6.74, 14.17), p<0.00001, I2=97%, random-effect modelling] (Figure 5B).\n\nConversion to open cholecystectomy\n\nA total of 27 studies (n=3,701) reported on the conversion to open cholecystectomy outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of conversion to open cholecystectomy rate [RR 1.07 (95% CI 0.53–2.19), p=0.84, I2=0%, random-effect modelling] (Figure 5C).\n\nLength of hospital stay\n\nA total of 26 studies (n=3,868) reported on the length of hospital stay outcome. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of length of hospital stay [MD -0.11 (95% CI -0.26, 0.05), p=0.18, I2=90%, random-effect modelling] (Figure 5D).\n\nVAS at four hours post-operation\n\nFive studies (n=537) reported on VAS at the four-hour post-operative observation. Our pooled analysis showed that the SILC procedure did not offer benefits in VAS at four hours post-operation when compared with the CMLC procedure [MD -0.70 (95% CI -1.89, 0.49), p=0.25, I2=95%, random-effect modelling] (Figure 6A).\n\nVAS at (A) 4, (B) 6, (C) 8, (D) 12 and 24 hours post-operation. Cosmesis at (F) one month and (G) six months post-operation. (H) Days to return to work. SILC, single-incision laparoscopic cholecystectomy; CMLC, conventional multi-port laparoscopic cholecystectomy; VAS, visual analog score.\n\nVAS at six hours post-operation\n\nNine studies (n=1,204) reported on VAS at the six-hour post-operative observation. Our pooled analysis showed that the SILC procedure offered benefits in reducing the VAS at six hours post-operation when compared with the CMLC procedure [MD -0.58 (95% CI -1.11, -0.05), p=0.03, I2=93%, random-effect modelling] (Figure 6B).\n\nVAS at eight hours post-operation\n\nFive studies (n=573) reported on VAS at the eight-hour post-operative observation. Our pooled analysis showed that the SILC procedure did not offer benefits in VAS at eight hours post-operation when compared with the CMLC procedure [MD -0.50 (95% CI -1.17, 0.17), p=0.15, I2=95%, random-effect modelling] (Figure 6C).\n\nVAS at 12 hours post-operation\n\nFour studies (n=459) reported on VAS at the 12-hour post-operative observation. Our pooled analysis showed that the SILC procedure did not offer benefits in VAS at 12 hours post-operation when compared with the CMLC procedure [MD -0.86 (95% CI -2.02, 0.30), p=0.15, I2=95%, random-effect modelling] (Figure 6D).\n\nVAS at 24 hours post-operation\n\nA total of 29 studies (n=4,096) reported on VAS at the 24-hour post-operative observation. Our pooled analysis showed that the SILC procedure did not offer benefits in VAS at 24 hours post-operation when compared with the CMLC procedure [MD -0.14 (95% CI -0.42, 0.14), p=0.32, I2=94%, random-effect modelling] (Figure 6E).\n\nCosmesis at one month\n\nFive studies (n=1,196) reported on the outcome of cosmesis one-month post-operation. Our pooled analysis showed that the SILC procedure offered benefits in increasing the cosmesis score one-month post-operation when compared with the CMLC procedure [SMD 2.12 (95% CI 1.10, 3.13), p<0.0001, I2=98%, random-effect modelling] (Figure 6F).\n\nCosmesis at six months\n\nThree studies (n=446) reported on the outcome of cosmesis six months post-operation. Our pooled analysis showed that the SILC procedure offered benefits in increasing the cosmesis score at six months post-operation compared with the CMLC procedure [SMD 0.53 (95% CI 0.06, 0.99), p=0.03, I2=81%, random-effect modelling] (Figure 6G).\n\nDays to return to work\n\nEight studies (n=771) reported on the days to return to work outcomes. Our pooled analysis showed that the SILC procedure did not differ from the CMLC procedure in terms of the number of days it took to return to work [MD 0.00 (95% CI -1.42, 1.43), p=1.00, I2=96%, random-effect modelling] (Figure 6H).\n\nMeta-regression\n\nMeta-regression was performed to identify risk factors that influence the relationship between SILC procedure and statistically significant outcomes, consisting of the operation time, VAS at six hours post-operation, cosmesis score at one-month post-operation, and cosmesis score at six months post-operation. The results of the meta-regression analyses can be found as Extended data.63 Our meta-regression revealed that variability in those outcomes in patients who underwent the SILC procedure compared with the CMLC procedure was explained by known patient factors associated with predictors of abdominal surgery outcomes. From our meta-regression analysis, it was revealed that the length of operation time in patients who underwent the SILC procedure compared with the CMLC procedure was not significantly influenced by age (p=0.1133), sex (p=0.1936), BMI (p=0.4407), and ASA score (p=0.0557). In terms of VAS at six hours post-operation, a statistically significant association was present for BMI (beta coefficient: -0.1120; 95% CI: -0.2161, -0.0079; p=0.0350). However, other factors such as age (p=0.7800), sex (p=0.8660), and ASA score (p=0.0976) did not significantly affect the relationship between the SILC procedure compared with the CMLC procedure on the VAS at six hours post-operation. Meanwhile, in terms of cosmesis at one-month post-operation, a statistically significant association was also present for BMI (beta coefficient: -1.2241; 95% CI: -1.7181, -0.7302; p<0.0001). Our meta-regression also revealed that cosmesis at one-month post-operation was not significantly influenced by age (p=0.2866), and sex (p=0.9090). Lastly, for cosmesis at six months post-operation, the meta-regression analysis could not be performed as there were too many included studies in the analysis.\n\nPublication bias\n\nWe used Funnel plot analysis for the assessment of publication bias in each outcome of interest. This analysis showed a relatively symmetrical inverted plot for all outcomes of interest in this study, indicating no publication bias.63 Furthermore, the Egger regression test results were also not statistically significant for all outcomes of interest, confirming the results from funnel plot analysis in which no sign of publication bias was found (Table 2).\n\n\nDiscussion\n\nThe current ‘gold standard’ for cholecystectomy is laparoscopic cholecystectomy. This well-known technique has superseded the open approach for routine cholecystectomy since the 1990s. Multiple studies have demonstrated that conventional laparoscopic (three or four ports) is feasible, safe, and favourable for cholecystectomy.61 Advancements in surgical technology are accelerating; thus, the single incision approach was introduced in 1997 to improve post-operative pain and cosmetic results. At present, SILC and CMLC are the current options for cholecystectomy with various considerations, and many RCTs showed the strengths and limitations of each technique, although the conclusion remains contentious.1\n\nA recent systematic review by Lyu et al.,12 stated that SILC did not offer advantages over CMLC. The overall results of our study showed that SILC improved post-operative pain and cosmetic results with no higher incidence of perioperative complications, blood loss, conversion to open cholecystectomy, extended hospital stay, and days return to work compared to CMLC. On the other hand, longer operation time is still a major issue of SILC.\n\nPerioperative complications are the current issue and remain disputable in every study. Evers et al.,7 in 2017 demonstrated that SILC was inferior to CMLC [RR 3.00 (95% CI 1.05–8.58)]. Another systematic review conducted by Hall et al.,11 further supported the inferiority of SILC regarding overall complications. Meanwhile, our study showed that biliary duct injuries, bile leakage, gall bladder perforation, wound infection, and incisional hernia did not differ between SILC and CMLC. These statements are parallel with other systematic reviews.9,13,62 Our suppositions are that the enhanced knowledge and advancement in single incision port have minimized the potential complications. Hence, SILC is considered as feasible as CMLC.\n\nThe learning curve that remains to be overcome for SILC is operation time. Our study demonstrated a longer time in SILC with a significant p-value. None of the other systematic reviews showed a quicker time in SILC than CMLC.7,9,11,13 Many aspects can hinder the operation time of SILC, including the peculiar technique, type of instruments, camera angle perspective, and instruments crossing. These issues can be overcome by surgical experience and the development of advanced instruments. Thus, the operation time may be equal in both approaches.\n\nPost-operative pain was calculated using the VAS at four time points (4, 6, 8, 12 and 24 hours). Our study showed a significant pain reduction at pain score six hours post-operation; however, VAS at 4, 8, 12 and 24 hours did not differ in both groups. The studies were done by Hall et al.,11 and Arezzo et al.,9 stated the VAS did not differ significantly. Meanwhile, Lirici et al.,62 demonstrated an improvement in VAS after day one, although the pain score on day one did not show any differences between SILC and CMLC. On the other hand, Evers et al.,7 revealed a superior VAS outcome in the SILC group at 24 hours. The opposite outcomes were reported by Lyu et al.,,12 in which SILC remained inferior for post-operative pain reduction at 6, 8, 12 and 24 hours. The heterogeneity of VAS was influenced by many elements, including the type of anaesthetic drugs, length of incision, and psychological factors. Thus, our study reported a high degree of heterogeneity.\n\nIn terms of cosmesis, the superiority of SILC was undoubtedly observed. Our study reported better cosmetic results at both the one-month and six-month post-operative outcomes. Multiple studies have also supported our results.7,9,11,62 The advantage of having a single incision at the umbilical creates a seamless scar, increasing the patient’s satisfaction. The definition of cosmesis was varied in every study; consequently, heterogeneity was high.\n\nOur study did not find any differences between SILC and CMLC concerning blood loss, conversion to open surgery, hospital stay, and days to return to work. Supporting studies also stated equivalent results, which SILC did not enhance the outcome of those categories.7,9,11,62\n\nThe limitations regarding this study are that we only included studies in English, a high degree of heterogeneity of several aspects, numerous RCTs with a high risk of bias, and inconsistent definitions of every outcome measured. We suggest an equal scoring for pain and cosmesis score to minimize the heterogeneity, as well as a more precise definition of perioperative complications and operation time to unify the outcome measurement. Hence, large-scale, double-blinded, well-designed RCTs are recommended.\n\n\nConclusions\n\nSILC is a safe, feasible and favourable approach. In terms of pain reduction and cosmetic results, SILC offers promising results. Thus, SILC may be an option for cholecystectomy depending on the surgeon’s experience.\n\n\nData availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nZenodo: Single-incision laparoscopic cholecystectomy versus conventional multi-port laparoscopic cholecystectomy: A systematic review, meta-analysis, and meta-regression of randomized controlled trials. https://doi.org/10.5281/zenodo.6416832.63\n\nThis project contains the following extended data:\n\n- ROB2_IRPG_beta_v9_Sysrev.xlsm (dataset)\n\n- Supplementary Figure 1.pdf\n\n- Supplementary Figure 2.pdf\n\n- Supplementary Figure 3.pdf\n\n- Supplementary Figure 4.pdf\n\n- Supplementary Table 1.docx\n\n- Search Strategy.docx\n\n\nReporting guidelines\n\nZenodo: PRISMA checklist for ‘Single-incision laparoscopic cholecystectomy versus conventional multi-port laparoscopic cholecystectomy: A systematic review, meta-analysis, and meta-regression of randomized controlled trials.’ https://doi.org/10.5281/zenodo.6416832.63\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nRudiman R: Minimally invasive gastrointestinal surgery: From past to the future. Ann. Med. Surg. 2021; 71: 102922–102928. Publisher Full Text\n\nHori T, Oike F, Furuyama H, et al.: Protocol for laparoscopic cholecystectomy: Is it rocket science? World J. Gastroenterol. 2016; 22(47): 10287–10303. PubMed Abstract | Publisher Full Text\n\nHaribhakti SP, Mistry JH: Techniques of laparoscopic cholecystectomy: Nomenclature and selection. J. Minimal Access Surg. 2015; 11(2): 113–118. PubMed Abstract | Publisher Full Text\n\nTranchart H, Ketoff S, Lainas P, et al.: Single incision laparoscopic cholecystectomy: for what benefit? HPB. 2013; 15(6): 433–438. PubMed Abstract | Publisher Full Text\n\nJoseph M, Phillips MR, Farrell TM, et al.: Single Incision Laparoscopic Cholecystectomy Is Associated With a Higher Bile Duct Injury Rate: A Review and a Word of Caution. Ann. Surg. 2012; 256(1): 1–6. PubMed Abstract | Publisher Full Text\n\nFurukawa K, Asaoka T, Mikamori M, et al.: Single-Incision Laparoscopic Cholecystectomy: a Single-Centre Experience of 1469 Cases. J. Gastrointest. Surg. 2022; 26: 831–836. PubMed Abstract | Publisher Full Text\n\nEvers L, Bouvy N, Branje D, et al.: Single-incision laparoscopic cholecystectomy versus conventional four-port laparoscopic cholecystectomy: a systematic review and meta-analysis. Surg. Endosc. 2017; 31(9): 3437–3448. PubMed Abstract | Publisher Full Text\n\nSajid MS, Ladwa N, Kalra L, et al.: Single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy: Meta-analysis and systematic review of randomized controlled trials. World J. Surg. 2012; 36(11): 2644–2653. PubMed Abstract | Publisher Full Text\n\nArezzo A, Scozzari G, Famiglietti F, et al.: Is single-incision laparoscopic cholecystectomy safe? Results of a systematic review and meta-analysis. Surg. Endosc. 2013; 27(7): 2293–2304. PubMed Abstract | Publisher Full Text\n\nSolhjou Z, Rezaianzadeh A, Bagherpourjahromi A, et al.: The early outcome of single-incision versus multi-port laparoscopic cholecystectomy. Adv. Biomed. Res. 2015; 4(1): 1–6.\n\nHall TC, Dennison AR, Dilraj BK, et al.: Single-Incision Laparoscopic Cholecystectomy A Systematic Review. Arch. Surg. 2012; 147(7): 657–666. Publisher Full Text\n\nLyu Y, Cheng Y, Wang B, et al.: Single-incision versus conventional multiport laparoscopic cholecystectomy: a current meta-analysis of randomized controlled trials. Surg. Endosc. 2020; 34(10): 4315–4329. PubMed Abstract | Publisher Full Text\n\nDaabiss M: American Society of Anaesthesiologists physical status classification. Indian J. Anaesth. 2011; 55(2): 111–115. PubMed Abstract | Publisher Full Text\n\nArezzo A, Passera R, Bullano A, et al.: Multi-port versus single-port cholecystectomy: results of a multi-centre, randomized controlled trial (MUSIC trial). Surg. Endosc. 2017; 31(7): 2872–2880. PubMed Abstract | Publisher Full Text\n\nBingener J, Skaran P, McConico A, et al.: A double-blinded randomized trial to compare the effectiveness of minimally invasive procedures using patient-reported outcomes. J. Am. Coll. Surg. 2015; 221(1): 111–121. PubMed Abstract | Publisher Full Text\n\nBorle FR, Mehra BK, Jain S: Evaluation of pain scores after single-incision and conventional laparoscopic cholecystectomy: a randomized control trial in a rural Indian population. Asian J. Endosc. Surg. 2014; 7(1): 38–42. PubMed Abstract | Publisher Full Text\n\nBrown KM, Moore BT, Sorensen GB, et al.: Patient-reported outcomes after single-incision versus traditional laparoscopic cholecystectomy: A randomized prospective trial. Surg. Endosc. 2013; 27(9): 3108–3115. PubMed Abstract | Publisher Full Text\n\nBucher P, Pugin F, Buchs NC, et al.: Randomized clinical trial of laparoendoscopic single-site versus conventional laparoscopic cholecystectomy. Br. J. Surg. 2011; 98(12): 1695–1702. PubMed Abstract | Publisher Full Text\n\nCao Z, Cai W, Qin MF, et al.: Randomized Clinical Trial of Single-Incision Versus Conventional Laparoscopic Cholecystectomy: Short-Term Operative Outcomes. Chin. Med. J. 2015; 128(24): 3310–3316.\n\nChang SKY, Wang YL, Shen L, et al.: A randomized controlled trial comparing post-operative pain in single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy. World J. Surg. 2015; 39(4): 897–904. PubMed Abstract | Publisher Full Text\n\nDeveci U, Barbaros U, Kapakli MS, et al.: The comparison of single incision laparoscopic cholecystectomy and three port laparoscopic cholecystectomy: Prospective randomized study. J. Korean Surg. Soc. 2013; 85(6): 275–282. PubMed Abstract | Publisher Full Text\n\nEllatif MEA, Askar WA, Abbas AE, et al.: Quality-of-life measures after single-access versus conventional laparoscopic cholecystectomy: A prospective randomized study. Surg. Endosc. 2013; 27(6): 1896–1906. PubMed Abstract | Publisher Full Text\n\nGoel A, Chaubey P, Gupta A, et al.: Comparative study of single-incision laparoscopic cholecystectomy with four-port conventional laparoscopic cholecystectomy: A single-center experience. World J. Laparosc. Surg. 2016; 9(1): 9–12. Publisher Full Text\n\nGuo W, Liu Y, Han W, et al.: Randomized trial of immediate postoperative pain following single-incision versus traditional laparoscopic cholecystectomy. Chin. Med. J. 2015; 128(24): 3310–3316. PubMed Abstract | Publisher Full Text\n\nHajong R, Hajong D, Natung T, et al.: A comparative study of single incision versus conventional four ports laparoscopic cholecystectomy. J. Clin. Diagn. Res. 2016; 10(10): PC06–PC09. PubMed Abstract | Publisher Full Text\n\nHe GL, Jiang ZS, Cheng Y, et al.: Tripartite comparison of single-incision and conventional laparoscopy in cholecystectomy: A multicenter trial. World J. Gastrointest. Endosc. 2015; 7(5): 540–546. PubMed Abstract | Publisher Full Text\n\nIto E, Takai A, Imai Y, et al.: Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial. Surgery (United States). 2019; 165(2): 353–359. Publisher Full Text\n\nJørgensen LN, Rosenberg J, Al-Tayar H, et al.: Randomized clinical trial of single- versus multi-incision laparoscopic cholecystectomy. Br. J. Surg. 2014; 101(4): 347–355. Publisher Full Text\n\nJusto-Janeiro JM, Vincent GT, Vázquez de Lara F, et al.: One, two, or three ports in laparoscopic cholecystectomy? Int. Surg. 2014; 99(6): 739–744. PubMed Abstract | Publisher Full Text\n\nKhorgami Z, Shoar S, Anbara T, et al.: A randomized clinical trial comparing 4-Port, 3-Port, and single-incision laparoscopic cholecystectomy. J. Investig. Surg. 2014; 27(3): 147–154. PubMed Abstract | Publisher Full Text\n\nKlein D, Görkem Barutcu A, Kröll D, et al.: Randomized controlled trial of single incision versus conventional multiport laparoscopic cholecystectomy with long-term follow-up.1911.\n\nKoirala A, Sulaimankulov R, Thakur D, et al.: Comparative Study of Single Incision Laparoscopic Cholecystectomy with Standard Four Port Laparoscopic Cholecystectomy for Symptomatic Cholelithiasis. Journal of KIST Medical College. 2019; 1(1): 10–14.\n\nLai ECH, Yang GPC, Tang CN, et al.: Prospective randomized comparative study of single incision laparoscopic cholecystectomy versus conventional four-port laparoscopic cholecystectomy. Am. J. Surg. 2011; 202(3): 254–258. PubMed Abstract | Publisher Full Text\n\nLeung D, Yetasook AK, Carbray J, et al.: Single-incision surgery has higher cost with equivalent pain and quality-of-life scores compared with multiple-incision laparoscopic cholecystectomy: A prospective randomized blinded comparison. J. Am. Coll. Surg. 2012; 215(5): 702–708. PubMed Abstract | Publisher Full Text\n\nLirici MM, Califano AD, Angelini P, et al.: Laparo-endoscopic single site cholecystectomy versus standard laparoscopic cholecystectomy: Results of a pilot randomized trial. Am. J. Surg. 2011; 202(1): 45–52. PubMed Abstract | Publisher Full Text\n\nLuna RA, Nogueira DB, Varela PS, et al.: A prospective, randomized comparison of pain, inflammatory response, and short-term outcomes between single port and laparoscopic cholecystectomy. Surg. Endosc. 2013; 27(4): 1254–1259. PubMed Abstract | Publisher Full Text\n\nLurje G, Raptis DA, Steinemann DC, et al.: Cosmesis and body image in patients undergoing single-port versus conventional laparoscopic cholecystectomy: A multicenter double-blinded randomized controlled trial (SPOCC-trial). Ann. Surg. 2015; 262(5): 728–735. PubMed Abstract | Publisher Full Text\n\nNoguera J, Tejada S, Tortajada C, et al.: Prospective, randomized clinical trial comparing the use of a single-port device with that of a flexible endoscope with no other device for transumbilical cholecystectomy: LLATZER-FSIS pilot study. Surg. Endosc. 2013; 27(11): 4284–4290. PubMed Abstract | Publisher Full Text\n\nPartelli S, Barugola G, Sartori A, et al.: Single-incision laparoscopic cholecystectomy versus traditional laparoscopic cholecystectomy performed by a single surgeon: findings of a randomized trial. Surg. Today. 2016; 46(3): 313–318. PubMed Abstract | Publisher Full Text\n\nQu JW, Xin C, Wang GY, et al.: Feasibility and safety of single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy in an ambulatory setting. Hepatobiliary Pancreat. Dis. Int. 2019; 18(3): 273–277. PubMed Abstract | Publisher Full Text\n\nRizwi F, Saleem M, Abid J: Outcome of Single Incision Laparoscopic Cholecystectomy (SILC) versus Conventional Four Port Laparoscopic Cholecystectomy for Cholelithiasis-A Randomized Control Trial. Pakistan J. Medical Health Sci. 2014; 8(1): 243–246.\n\nSaad S, Strassel V, Sauerland S: Randomized clinical trial of single-port, minilaparoscopic and conventional laparoscopic cholecystectomy. Br. J. Surg. 2013; 8: 339–349.\n\nSasaki A, Ogawa M, Tono C, et al.: Single-Port Versus Multiport Laparoscopic Cholecystectomy: A Prospective Randomized Clinical Trial. Surg. Laparosc. Endosc. Percutan. Tech. 2012; 22(5): 396–399. PubMed Abstract | Publisher Full Text\n\nSolomon D, Shariff AH, Silasi DA, et al.: Transvaginal cholecystectomy versus single-incision laparoscopic cholecystectomy versus four-port laparoscopic cholecystectomy: A prospective cohort study. Surg. Endosc. 2012; 26(10): 2823–2827. PubMed Abstract | Publisher Full Text\n\nSubirana H, Rey F, Barri J, et al.: Single-incision versus four-port laparoscopic cholecystectomy in an ambulatory surgery setting: A prospective randomized double-blind controlled trial. J. Minimal Access Surg. 2021; 17(3): 311–317. PubMed Abstract | Publisher Full Text\n\nSulu B, Yildiz BD, Ilingi ED, et al.: Single port vs. four port cholecystectomy - Randomized trial on quality of life. Adv. Clin. Exp. Med. 2015; 24(3): 469–473. PubMed Abstract | Publisher Full Text\n\nYe G, Qin Y, Xu S, et al.: Comparison of transumbilical single-port laparoscopic cholecystectomy and fourth-port laparoscopic cholecystectomy. Int. J. Clin. Exp. Med. 2015; 8(5): 7746–7753. PubMed Abstract\n\nYilmaz H, Arun O, Apiliogullari S, et al.: Effect of laparoscopic cholecystectomy techniques on postoperative pain: A prospective randomized study. J. Korean Surg. Soc. 2013; 85(4): 149–153. PubMed Abstract | Publisher Full Text\n\nZhao L, Wang Z, Xu J, et al.: A randomized controlled trial comparing single-incision laparoscopic cholecystectomy using a novel instrument to that using a common instrument. Int. J. Surg. 2016; 32: 174–178. PubMed Abstract | Publisher Full Text\n\nZheng M, Qin M, Zhao H: Laparoendoscopic single-site cholecystectomy: A randomized controlled study. Minim. Invasive Ther. Allied Technol. 2012; 21(2): 113–117. PubMed Abstract | Publisher Full Text\n\nAprea G, Rocca A, Salzano A, et al.: Laparoscopic single site (LESS) and classic video-laparoscopic cholecystectomy in the elderly: A single centre experience. Int. J. Surg. 2016; 33: S1–S3. PubMed Abstract | Publisher Full Text\n\nKumar S, Ahmad Z: Single port laparoscopic cholecystectomy compared to the standard laparoscopic cholecystectomy. Int. Surg. J. 2019; 6: 1348. Publisher Full Text\n\nMa J, Cassera MA, Spaun GO, et al.: Randomized Controlled Trial Comparing Single-Port Laparoscopic Cholecystectomy and Four-Port Laparoscopic Cholecystectomy. Ann. Surg. 2011; 254: 22–27. PubMed Abstract | Publisher Full Text\n\nMadureira FAV, Manso JEF, Madureira Fo D, et al.: Randomized clinical study for assessment of incision characteristics and pain associated with LESS versus laparoscopic cholecystectomy. Surg. Endosc. 2013; 27: 1009–1015. PubMed Abstract | Publisher Full Text\n\nMarks JM, Phillips MS, Tacchino R, et al.: Single-Incision Laparoscopic Cholecystectomy Is Associated with Improved Cosmesis Scoring at the Cost of Significantly Higher Hernia Rates: 1-Year Results of a Prospective Randomized, Multicenter, Single-Blinded Trial of Traditional Multiport Laparoscopic Cholecystectomy vs Single-Incision Laparoscopic Cholecystectomy. J. Am. Coll. Surg. 2013; 216: 1037–1047.\n\nOmar MA, Redwan AA, Mahmoud AG: Single-incision versus 3-port laparoscopic cholecystectomy in symptomatic gallstones: A prospective randomized study. Surgery. 2017; 162: 96–103. PubMed Abstract | Publisher Full Text\n\nPan MX, Jiang ZS, Cheng Y, et al.: Single-incision vs three-port laparoscopic cholecystectomy: Prospective randomized study. World J. Gastroenterol. 2013; 19: 394–398. PubMed Abstract | Publisher Full Text\n\nSinan H, Demirbas S, Ozer MT, et al.: Single-incision Laparoscopic Cholecystectomy Versus Laparoscopic Cholecystectomy. Surg. Laparosc. Endosc. Percutan. Tech. 2012; 22: 12–16. Publisher Full Text\n\nTyagi S, Sinha R, Tyagi A: Single incision laparoscopic cholecystectomy: Less scar, less pain. J. Minimal Access Surg. 2017; 13: 118–123. PubMed Abstract | Publisher Full Text\n\nZapf M, Yetasook A, Leung D, et al.: Single-incision results in similar pain and quality of life scores compared with multi-incision laparoscopic cholecystectomy: A blinded prospective randomized trial of 100 patients. Surgery. 2013; 154: 662–671. PubMed Abstract | Publisher Full Text\n\nHassler KR, Collins JT, Philip K, et al.: Laparoscopic Cholecystectomy. StatPearls Publishing.\n\nLirici MM, Tierno SM, Ponzano C: Single-incision laparoscopic cholecystectomy: does it work? A systematic review. Surg. Endosc. 2016; 30(10): 4389–4399. PubMed Abstract | Publisher Full Text\n\nRudiman R, Hanafi RV, Almawijaya.: Single-incision laparoscopic cholecystectomy versus conventional multi-port laparoscopic cholecystectomy: A systematic review, meta-analysis, and meta-regression of randomized controlled trials [Dataset]. Zenodo. 2022. Publisher Full Text"
}
|
[
{
"id": "155047",
"date": "07 Feb 2024",
"name": "Vicky Sumarki Budipramana",
"expertise": [
"Reviewer Expertise Gastroentestinal surgery"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn Fig. 1 regarding PRISMA flowchart, section “Reports excluded: Exclusion criteria (n = 10)” were not clearly detailed into some points and the number of the excluded studies in each of the exclusion criteria. It will be better to input the detailed information to avoid misunderstandings among readers regarding the exclusion criteria.\n\nIn I2 statistic’s cut-off values, the authors stated three categories: <25%, 26-50%, and >50%. “26-50%” should have been “25-50%”, shouldn't it? Please correct the written cut-off to prevent misinterpretation if the I2 = 25%.\n\nThe figure legends of Fig. 3 to Fig. 6 should have been clearly stated regarding the classification of the outcomes. Why were the figures separated into Fig. 3 to Fig. 6? Since the outcomes should have been only classified into three (feasibility, safety, and surgical outcome). This should also have gone to the “Outcome effect” section in the results. Please clasify the outcomes in the results section based on the primary goal of this study in order for the readers to understand the outcomes easily.\n\nPlease explain the novelty of this study as compared with reference No. 12 since it also carries the similar title to the current study.\n\nIn the discussion section, in paragraph 6, the authors are encouraged to add an explanation regarding the fact that cosmesis is influenced by BMI based on the meta-regression analysis. This is an interesting finding that should have been revealed in the discussion section.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "335341",
"date": "06 Nov 2024",
"name": "Yunushan Furkan Aydoğdu",
"expertise": [
"Reviewer Expertise General Surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral Evaluation Subject and Objective: The study focused on the comparison of SILC and CMLC techniques. The purpose of the research is clearly defined and targets existing gaps in the literature. This draws the reader's attention.\nMethods: The methods section clearly describes the systematic review and meta-analysis processes. A specific framework is established with PICOS criteria. The search strategy and study selection process are described in detail.\nResults: The results section presented the analyzed data in a systematic way. Statistical data are well summarized, but could be strengthened with more visual support (graphs or tables).\nDiscussion: The discussion section provides a good overview of the relevance of the findings to the existing literature. The advantages and disadvantages of SILC are clearly discussed. However, some sentences may need to be simplified to improve fluency.\nRecommendations Expansion of Limitations: The limitations section could be enriched by adding more detail. For example, more emphasis could be placed on the potential impacts of the language limitation in the study.\nSummarizing the Results: At the end of the study, it may be useful to provide a brief summary of the main findings and recommendations for future research. This makes it easier for readers to remember the main points.\nReferences and Citations: The use of references in more contexts throughout the study may increase the credibility of the text. (As a suggestion regarding the study I am reviewing, I would like to state that the article by Aydoğdu et al. (2024) titled “Minimally invasive approach in a rare emergency surgery, gallbladder perforation” should also be included in the evaluation. This study highlights the efficacy of minimally invasive approaches for a rare surgical emergency such as gallbladder perforation. )\nConclusion Overall, the paper is well structured and provides important insights on the topic.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": [
{
"c_id": "12792",
"date": "08 Nov 2024",
"name": "Reno Rudiman",
"role": "Author Response",
"response": "Dear Dr. Yunushan Furkan Aydoğdu, Thank you for your insightful recommendations on our manuscript. Therefore, we will proceed to revise based on the details you have provided. Best regards Rudiman"
}
]
}
] | 1
|
https://f1000research.com/articles/11-754
|
https://f1000research.com/articles/13-1119/v1
|
03 Oct 24
|
{
"type": "Case Report",
"title": "Case Report: Hymenolepis diminuta in an asymptomatic Ecuadorian child.",
"authors": [
"Zulbey Rivero de Rodriguez",
"Ader Ponce",
"Anthony Vera",
"Angela Bracho",
"Anita Murillo",
"Ader Ponce",
"Anthony Vera",
"Angela Bracho",
"Anita Murillo"
],
"abstract": "Background The cestode Hymenolepis diminuta is a cosmopolitan parasite, which in the adult stage is usually found in the small intestine of rats and accidentally in humans.\n\nCase report We describe the finding of eggs of this parasite in an asymptomatic 3-year-old child. The child had extremely high IgE values of 1,376 IU/ml. After receiving treatment with Albendazole suspension 400mg/20mL, on the 10th day post-treatment, he showed no H. diminuta eggs in his fecal matter\n\nConclusions Detailed morphological review of Hymenolepis nana-like eggs is recommended to distinguish them from H. diminuta eggs.",
"keywords": [
"Hymenolepis diminuta",
"asymptomatic condition",
"Child",
"Preschool",
"Ecuador"
],
"content": "Introduction\n\nThe cestode Hymenolepis diminuta (Rudolphi 1819, Weinland 1858) is a cosmopolitan parasite, which in the adult stage is usually found in the small intestine of rats and accidentally in humans. Its biological cycle develops with the intervention of an arthropod, which becomes infected by ingesting the eggs of H. diminuta, which are found in the feces of parasitized rats.1\n\nThe mechanism of infection begins when coprophilic arthropods ingest the eggs of H. diminuta eliminated by rodent feces and act as obligate intermediate hosts of the cestode. When humans accidentally ingest these infected arthropods, the cysticercoids present in the insect’s hemocele develop to adults in the human’s small intestine, where eggs are then produced and expelled in defecation. Human infection through direct ingestion of H. diminuta eggs has not been reported to date.2\n\nSeveral coprophilous arthropods such as fleas, weevils, lepidoptera and beetles have been described as intermediate hosts,3 as well as different species of beetles of the genera Tribolium and Tenebrio.4 Experimentally, it has been shown that 90 species of arthropods can serve as intermediate hosts.5 Although, Joyeux6 pointed to Tenebrio molitor, Ceratophyllus fasciatus and Xenopsylla cheopis as the usual sources of rat infestation, the beetles of the genus Tribolium are those indicated by the scientific literature, as the most frequent in rat and human infections.\n\nThe adult cestode of H. diminuta is 20 to 60 cm long, its scolex is rounded and small with four cup-shaped suckers, it has a rostellum without hooks, which is invaginated in a cavity located in the most apical portion of the scolex. The strobilar chain contains three characteristic portions of proglottids: immature, mature, and gravid; The latter, when detached from the strobilus, disintegrate and release the eggs that are eliminated along with the feces.7 The eggs are rounded, 60 to 80 microns in size, yellowish in color with a thick outer membrane and a smaller oncosphere inside, with three pairs of hooks and no polar filaments.8\n\nClinically, as in Hymenolepis nana infection, parasitosis can be asymptomatic. In infections with a high parasite load, the most frequent symptoms of H. diminuta hymenolepiasis are digestive, with abdominal pain and diarrhea prevailing; irritability and anal itching may also occur2,3,9 and in some cases patients with skin conditions have presented.10,11\n\nIt is an uncommon infection in humans; however, the prevalence is high in some places: 7.8% in schoolchildren between 6 and 15 years of age in Magdalena in Cajamarca12 and 7.1% in the population of Tingo María in Huánuco in Peru.13 It can be deduced that food, stored and in contact with rats and beetles, when consumed constitutes the means of infection, by ingestion of infected beetles. There are few cases in the literature that report infections in adults3 since most have been described in children,2,9–11,14–17 probably due to ingesting the infected arthropods without realizing it. However, a 2020 review of H. diminuta18 states that, out of 130 infections in humans, the age of the infected individuals was: 2.3% infants (≤1 year old), 66.2% children (2 to 9 years), 20% adolescents (10 to 19 years old), and 11.5% were adults (≥ 20 years old).\n\nRegarding geographical location, the review by Panti-May et al.18 reports that human infections with H. diminuta were reported in 80 countries around the world from 1810 to 2018. Most cases were reported in the Americas (n = 815), Southeast Asia (n = 226) and Eastern Mediterranean (n = 210). Three countries exhibited more than 100 records: Costa Rica (n = 320), the United States of America (n = 181), and Brazil (n = 140).\n\nIn Ecuador, the presence of Hymenolepis spp. has been described19 in stray dogs on the coastal beaches of Ecuador, Hymenolepis nana and diminuta have also been reported in rodents (Rattus norvegicus and Rattus rattus) from the city of Milagro.20 Only one case has previously been reported of this species in a two-year-old Ecuadorian girl, however, the finding was made in Spain11; This case describes that in 2003 it arrived in that continent and in the first half of 2004 it presented gastrointestinal symptoms, detecting the parasite in feces. In 2007, research by Jacobsen et al.21 indicated a 1% prevalence of H. diminuta when evaluating 203 samples from children between 12 and 60 months of age; however, no reference was made to clinical or sociodemographic data of the infected child (ren). Since then, no other case of infection in humans has been described in the country, so the case of an asymptomatic child from Portoviejo, Ecuador, is presented.\n\n\nCase report\n\nIn February 2024, the stool sample of a 3-year-old child is received at the Parasitology laboratory of the Technical University of Manabí. On macroscopic examination, the sample showed a soft, greenish-brown consistency, without mucus, pus, or blood; There are also no obvious food residues. Microscopic examination with physiological saline, showed eggs morphologically compatible with eggs of Hymenolepis diminuta (Figure 1A,B). These had their characteristic brown color, large size and absence of polar filaments. They were measured with a micrometer scale, where 4 of them measured 60 microns and 1 measured 70 microns in diameter.\n\nWhen the father is consulted, he indicates that the child did not have gastrointestinal symptoms and that the stool test was carried out as part of the annual health evaluation that he performs. When reviewing the rest of the tests performed, it was observed in the hematology: Leukocyte count within the reference values: 7.15×102/μl (5.0 to 10.00), but with a decrease in neutrophils: 1.59×102/μl (2.10 to 8.90), an increase in lymphocytes: 4.64×102/μl (1.30 to 4.60) and a slight increase in eosinophils: 5.2% (0.0 to 4.0). Hemoglobin 12.5 g/dl (10.5 to 13.5 g/dl), Hematocrit: 36.0% (32.0 to 40.0%). The results show that, although C-reactive protein was within the reference values: 0.33 mg/L (0.00 to 5.00 mg/L), there was a significant increase in the value of Immunoglobulin E (IgE): 1.376 IU/ml (0.0 to 60.0 IU/ml).\n\nTo assess the child’s living conditions, his home was visited. The house is in a peri-urban community of the city of Portoviejo (Colón parish). Although Colón is considered an urban parish, the house is in a wooded area of the parish, and in the back has an abundance of intricate trees. In general terms, the house is neat and has the basic services of water, electricity, and septic tank, for the disposal of excreta. There is a chance of rats and mice in the back wooded area, which is ideal for synanthropic animals. During the visit, the presence of beetles (genus Hexodon) is observed and since there are dogs, the presence of fleas, which have been described as intermediate hosts of H. diminuta, cannot be ruled out.\n\nThe child received anthelmintic treatment with Albendazole suspension 400 mg/20 mL, 2 bottle, one per day. On the 4th day after treatment, a post-treatment stool examination was performed and eggs were still observed, which were quite altered in their morphology and difficult to identify. Subsequently, 10 days after the end of treatment, the stool examination showed no evolutionary forms of parasites.\n\n\nDiscussion\n\nHymenolepis diminuta infection is a cosmopolitan zoonosis that is mainly rural and infrequent in humans. As of 2020, 1,561 published records of H. diminuta infection had been identified in 80 countries18; mainly reported in children.2,9–11,14–17\n\nAlthough the child in this case did not present clinical manifestations and most of his laboratory tests were within the reference ranges, the high IgE value found is remarkable. The child does not suffer from allergies, so this situation was ruled out as the cause of the increase. Helminth infections have been mainly related to blood eosinophilia22–24 and a similar situation has only been reported in terms of increased IgE in a child with H. diminuta in Italy10 who presented atypical allergic manifestations.11 In this research, it is pointed out that the infected 2-year-old child presented remitting fever (maximum peak 37.7 °C), abdominal pain, diffuse skin itching, transient chest rash and arthromyalgia and in the same context, the case of the Ecuadorian girl in Spain is presented, who manifested atopic dermatitis, self-limited diarrhea, vomiting and constipation, unlike the current case. there were no allergic manifestations or any symptoms, only the elevation of IgE.\n\nAllergic symptoms are often present in chronic helminth infections, caused by a constant state of immune activation characterized by a dominant type of Th2 cytokine profiles and high IgE levels.25,26 However, eosinophilia is not usually seen in helminth infections that reside in the lumen of the human intestine, as is the case with H. diminuta. However, helminth infections can affect the expression of an allergic disease and, in certain situations, may be associated with a higher, lower, or no risk of atopic conditions.27,28\n\nAnother important point to highlight is the anthelmintic treatment applied, since the literature reports that the first choice anthelmintics are praziquantel and niclosamide,3 therefore, it has been the treatment of choice in several studies.9–11,14–17 However, in this case, albendazole was indicated, a treatment also applied in a case reported by Rivero et al.2 in Venezuela, demonstrating effectiveness in the treatment of parasitosis, as no eggs were observed in successive samples. It is known that first-choice drugs are given in single doses, however, Tena et al.14 indicated in their study to repeat the dose three times, even increased, until the parasite was eliminated, so albendazole can be considered as an alternative treatment.\n\n\nConclusions\n\nIt is feasible to find H. diminuta infection in Ecuadorian children, although in an infrequent way, so the microscopist should be alert to the finding of eggs like those of Hymenolepis nana, but larger and dark brown in fresh preparations. Likewise, medical personnel should not rule out the possibility of this parasitic species in children, mainly under five years of age.\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the parent relative of the patient. Written informed consent has been obtained from the father of the patient to publish this paper. Informed assent could not be obtained, because the child was very young (3 years old).",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nTo the Ponce Bazurto family for their collaboration in providing all the necessary information about the case.\n\n\nReferences\n\nRoberts JJ, Schmidt G, Larry S: Roberts’Foundations of Parasitology. 8th ed.McGraw-Hill; 2009; 701.\n\nRivero ZC, Villalobos R, Bracho A, et al.: Infección por Hymenolepis diminuta en un niño del municipio Maracaibo, estado Zulia, Venezuela. Rev. Soc. Venez. Microbiol. 2009; 29: 133–135.\n\nMartínez-Barbabosa I, Gutiérrez-Cárdenas M, Aguilar-Venegas J, et al.: Infección por Hymenolepis diminuta en una estudiante universitaria. Rev. Biomed. 2012; 23: 61–64.\n\nShostak A: Hymenolepis diminuta infections in tenebrionid beetles as a model system for ecological interactions between helminth parasites and terrestrial intermediate hosts: A review and meta-analysis. J. Parasitol. 2014; 100(1): 46–58. PubMed Abstract | Publisher Full Text\n\nCáceres I, Guillén Z: Insectos de Lima relacionados con el cisticercoide de Hymenolepis diminuta (Rudolphi, 1819), (Cestoda: Hymenolepididae). Rev. Per. Entom. 1972; 15(1): 142–147.\n\nJoyeux C: Sur le cycle evolutif de quelques Cestodes. Bull. Soc. Pathol. Exot. 1916; 9: 578–583.\n\nTay J, Gutiérrez M, Lara R, et al.: Parasitología Médica. 8ª ed.México: Méndez Editores; 2010; pp. 227–232.\n\nBotero D, Restrepo M: Parasitosis Humanas. 6ª ed.Fondo editorial CIB; 2019; p. 412.\n\nKołodziej P, Rzymowska J, Stępień-Rukasz H, et al.: Analysis of a child infected with Hymenolepis diminuta in Poland. Ann. Agric. Environ. Med. 2014; 21(3): 510–511. PubMed Abstract | Publisher Full Text\n\nMarangi M, Zechini B, Fileti A, et al.: Hymenolepis diminuta infection in a child living in the urban area of Rome, Italy. J. Clin. Microbiol. 2003; 41: 3994–3995. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartínez-Peinado C, López-Perezagua M, Arjona-Zaragozí FJ, et al.: Parasitosis en niña ecuatoriana. Enferm. Infecc. Microbiol. Clin. 2006; 24(3): 207–208. PubMed Abstract | Publisher Full Text\n\nNáquira C, Delgado D, Tantaleán M, et al.: Prevalencia de enteroparásitos en escolares de los distritos de San Juan y Magdalena (Departamento de Cajamarca) 1971. Rev. Per. Med. Trop. U.N.M.S.M. 1973; 2: 37–41.\n\nHuiza A, Tantaleán M, Juárez D: Observaciones sobre la presencia de enteroparásitos en la región de Rupa Rupa, departamento de Huanuco. Bol. Med. Trop (Lima). 1986; 5: 7–9.\n\nTena D, Pérez SM, Gimeno C, et al.: Human Infection with Hymenolepis diminuta: Case Reporty from Spain. J. Clin. Microbiol. 1998; 36: 2375–2376. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatamia I, Cappello E, Castellano-Chiodo D, et al.: A human case of Hymenolepis diminuta in a child from eastern Sicily. Korean J. Parasitol. 2010; 48: 167–169. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRohela M, Ngui R, Lim YA, et al.: case report of Hymenolepis diminuta infection in a Malaysian child. Trop. Biomed. 2012; 29(2): 224–230. PubMed Abstract\n\nSinhabahu VP, Perera TM, Samarasinghe S, et al.: A case of Hymenolepis diminuta (rat tape worm) infestation in a child. Ceylon Med. J. 2014; 59(2): 70–71. PubMed Abstract | Publisher Full Text\n\nPanti-May JA, Rodríguez-Vivas RI, García-Prieto L, et al.: Worldwide overview of human infections with Hymenolepis diminuta. Parasitol. Res. 2020; 119(7): 1997–2004. PubMed Abstract | Publisher Full Text\n\nCalvopina M, Cabezas-Moreno M, Cisneros-Vasquez E, et al.: Diversity and prevalence of gastrointestinal helminths of free-roaming dogs on coastal beaches in Ecuador: Potential for zoonotic transmission. Vet. Parasitol. Reg. Stud. Reports. 2023; 40: 100859. PubMed Abstract | Publisher Full Text\n\nCoello-Peralta R, Martínez-Cepeda G, Pinela-Castro D, et al.: Presencia de Hymenolepis nana y diminuta en roedores de la ciudadela las Piñas, Milagro-Ecuador y su riesgo en salud pública. Rev. Mex. Cienc. Pecu. 2020; 11(4): 961–970. Publisher Full Text\n\nJacobsen K, Ribeiro P, Quist B, et al.: Prevalence of Intestinal Parasites in Young Quichua Children in the Highlands of Rural Ecuador. J. Health Popul. Nutr. 2007; 25(4): 339–405.\n\nSteer M, Preston S, Piedrafita D, et al.: The Immune Response to Nematode Infection. Int. J. Mol. Sci. 2023; 24(3): 2283. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarranza-Rodríguez C, Escamilla-González M, Fuentes-Corripio I, et al.: Helmintosis y eosinofilia en España (1990-2015). Enf. Infecciosas Microbiol. Clín. 2018; 36(2): 120–136. PubMed Abstract | Publisher Full Text\n\nMurillo-Zavala A, Molina-Solorzano A, Peñafiel-Álvarez D: Helmintiasis intestinal, eosinofilia e inmunomodulación parasitaria. Kasmera. 2022; 50: e5034307. Publisher Full Text\n\nRobinson TM, Nelson RG, Boyer JD: Parasitic infection and the polarized Th2 immune response can alter a vaccine-induced immune response. DNA Cell Biol. 2003; 22: 421–430. PubMed Abstract | Publisher Full Text\n\nPalmer LJ, Celedon JC, Weiss ST, et al.: Ascaris lumbricoides is associated with increased risk of childhood asthma and atopy in rural China. Am. J. Respir. Crit. Care Med. 2002; 165: 1489–1493. PubMed Abstract | Publisher Full Text\n\nCooper PJ, Chico ME, Bland M, et al.: Alllergic symptoms, atopy, and geohelminth infections in a rural area of Ecuador. Am. J. Respir. Crit. Care Med. 2003; 168: 313–317. PubMed Abstract | Publisher Full Text\n\nWiwanitkit V: Overview of Hymenolepis diminuta infection among Thai patients. Medscape Gen. Med. 2004; 6: 7. PubMed Abstract"
}
|
[
{
"id": "331922",
"date": "28 Oct 2024",
"name": "Yukifumi Nawa",
"expertise": [
"Reviewer Expertise Parasitology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral: Although this manuscript is a case report of asymptomatic Hymenoleepis diminuta infection in a child in Ecuador, actual content of this manuscript is a kind of the mixture of a case report and a insufficient review of H. diminuta infection in general. Thus, as a case report, the entire manuscript is lengthy and wordy with too much of unnecessary reference citation.\nSpecific: Introduction This is a report of an asymptomatic hymenolepiasis case. Thus, this case has little significance/attractive issues in terms of clinical practice. Also, as is mentioned by the authors, H. diminuta infection in humans, especially among children of poor sanitary condition has been sporadically but repeatedly reported from various parts of the world. The only merit/appeal of this case report is the confirmed case of H. diminuta infection in a child in Ecuador, where the presence of such a parasitic disease is ignored by the clinical practitioners in the country. Thus, the first 4 paragraphs of general description of H. diminuta infection should be merged into one short introductory paragraph.\nCase report The 3 years old boy has received regular health checking and his stool sample was examined in the Parasitology Laboratory. However, his stool was examined only by direct microscopic observation for the saline-diluted specimen (Please give more data as to how much of stool with what degree of saline-dilution). What about other coproparasitological examinations? What about possible co-infection with other intestinal helminths or protozoa?\nDiscussion The same problem as those seen in the Introduction. The Discussion part of the case report should be limited to the findings and the problems and the tasks directly related to the present case. As it stands, the Discussion section of this manuscript contains too much of general information not directly related to this cs.\nConclusions As it stands, the Conclusion is too general. Conclusions of the case report should be specific from the observations of this case.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "12803",
"date": "18 Nov 2024",
"name": "Zulbey Rivero de Rodriguez",
"role": "Author Response",
"response": "1.-The reviewer's suggestion is respected, but changes were made to the introduction, as it is considered short enough that it is necessary to eliminate information that is important to provide to the reader. 2.- Information on stool tests is included, because if we had the concentrate result and forgot to put that in the article 3.- The discussion further discussed the increase in eosinophils and IgE in cases of H. diminuta, such as this one. It was added that unfortunately there was no data on post-treatment IgE. 4.- Something else is added for conclusion, taking into account the reviewer's suggestion"
}
]
},
{
"id": "331924",
"date": "04 Nov 2024",
"name": "Adriana Esteves",
"expertise": [
"Reviewer Expertise Molecular parasitology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe Case Report: Hymenolepis diminuta in an asymptomatic Ecuadorian child from Rivero and coworkers is very interesting in that it shows an atypical case of a parasitosis in a patient. The data provided in the introduction is correct and very appropriate.\nRecommendations to the authors:\n\nExplain the meaning of “direct ingestion of eggs” I understand that its different from accidentally, but it is difficult to understand a voluntary ingestion. “… probably due to ingesting the infected arthropods without realizing it.” The explanation is not convincing. The indicated period of reports around the world is too long to have an idea of the evolution of the disease. It would be appropriate to indicate, for example, the current prevalence in each country mentioned, or at least some way that allows such old cases to be evidenced by recent ones. What’s the meaning of (ren) at the end of a sentence from the last paragraph of the introduction. IgE data after treatment would be an important input complementing the microscopic evaluation. If you have them, I suggest including them “… unlike the current case. there were no allergic manifestations ….“Typing error, there should be a comma instead of a period.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "12802",
"date": "18 Nov 2024",
"name": "Zulbey Rivero de Rodriguez",
"role": "Author Response",
"response": "1.-When direct ingestion of eggs is indicated, it means ingestion of the eggs as such, not in any other evolutionary way. It means that even if an egg is swallowed, infection has not been described. It is necessary to ingest the cysticercoid found inside an arthropod.If you think it is strictly necessary to explain this better, please let me know. 2.-In the part where it is indicated that children are more susceptible to infection, it was changed without realizing it, because without paying attention to it. 3.- The placement of child(ren) was to indicate the plural of child, but it was changed at once to children 4.-We do not have IgE data from the child after treatment, as far as we know only stool tests were done again (we did them) 5.-Corrected, the period (dot) was removed and a comma was placed"
}
]
}
] | 1
|
https://f1000research.com/articles/13-1119
|
https://f1000research.com/articles/13-1382/v1
|
18 Nov 24
|
{
"type": "Study Protocol",
"title": "Methodological literature on the reporting of systematic reviews of health economic evaluations: a scoping review protocol",
"authors": [
"Phuong Bich Tran",
"Joseph Kwon",
"Anastasios Bastounis",
"Stavros Petrou",
"Andrew Booth",
"PRISMA-EconEval Management Group",
"Joseph Kwon",
"Anastasios Bastounis",
"Stavros Petrou",
"Andrew Booth"
],
"abstract": "Systematic reviews of health economic evaluations play a crucial role in informing evidence-based healthcare decisions, yet they lack standardized reporting guidelines. A project has been initiated that aims to extend the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for systematic reviews of health economic evaluations (PRISMA-EconEval). This scoping review forms a foundation for the PRISMA-EconEval project, aiming to identify, map, and extract candidate reporting items from the methodological literature. The scoping review will follow the PRISMA Extension for Scoping Reviews (PRISMA-ScR) Checklist and involve comprehensive searches in databases such as PubMed MEDLINE, Embase, and Web of Science, covering the period from 2015 to 2024. Supplementary searching, reference checking and citation searching will target grey literature, overlooked studies and evidence prior to 2015. Inclusion criteria will focus on methodological papers that provide frameworks or recommendations for reporting systematic reviews of health economic evaluations and enhanced case studies that critically discuss methods and reporting structures. The extracted data will be coded and analyzed to produce an initial list of candidate reporting items, structured according to conventional sections of a systematic review (e.g., title, abstract, methods, results). This initial list will be used in the subsequent stages of the project and disseminated through a peer-reviewed publication and presentations at international conferences. The outcome of this scoping review will significantly contribute to the development of a comprehensive PRISMA-EconEval reporting guideline, aimed at enhancing the transparency, consistency, and quality of systematic reviews of health economic evaluations, and provide an essential tool for authors, editors, peer-reviewers, and stakeholders.",
"keywords": [
"reporting",
"systematic review",
"health economic evaluation",
"review protocol"
],
"content": "Introduction\n\nA systematic review summarizes the available evidence and provides an unbiased, reliable assessment of the current state of knowledge, essential for making evidence-based decisions.1 The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement was designed to enhance the reporting of systematic reviews and meta-analyses – primarily of the effects of interventions, though also applicable to systematic reviews and meta-analyses of studies with a different objective – by improving their clarity, consistency, transparency, quality, and overall value.2\n\nSystematic reviews of health economic evaluations differ from other systematic reviews in their approach to reporting key methodological steps, including methods for study selection, data extraction and presentation, and the assessment of quality and relevance. Such reviews consider health economic evaluations, which compare the effects of different healthcare interventions on economic outcomes (e.g. incremental cost-effectiveness ratios, net monetary benefits, etc.). Additionally, they differ in their potential for combining costs, preference-based health-related quality of life outcomes, and cost-effectiveness outcomes across studies.\n\nA literature search in PubMed Central from January 1, 2015 to March 25, 2017 found 202 systematic reviews of health economic evaluations listed within this 27-month period.3 Extending the search to other databases and grey literature and from 2017 to date is likely to increase this number substantially. These reviews lack common standards for reporting quality, highlighting the need for an additional reporting guideline specifically for systematic reviews of health economic evaluations.\n\nThe ‘Development of a PRISMA extension for systematic reviews of health economic evaluations (PRISMA-EconEval)’ project was initiated to address this gap. A core international multidisciplinary working group, including PRISMA members, authors, journal editors, and stakeholders, will identify and extract candidate reporting items from various sources. Such sources include this scoping review of the methodological literature on the reporting of systematic reviews of health economic evaluations together with a purposive sample of previous systematic reviews of health economic evaluations. They will refine these items to improve reporting quality. A multi-round online Delphi survey will then evaluate these items with input from academic researchers, specifically health economists (including authors of systematic reviews of health economic evaluations) and systematic review methodologists, journal editors, reporting guideline developers, information specialists, and stakeholders, including health care decision-makers, health research funders, and patient and public representatives. The development of common reference standards for reporting should enhance completeness, transparency and structure in the reporting of systematic reviews of health economic evaluations and generate user-friendly tools for authors, editors, peer-reviewers and stakeholders that facilitate reporting.\n\nAs a first step, it is necessary to review the methodological literature on the reporting of systematic reviews of health economic evaluations. This process will help map the current methods, guidance, and recommendations for reporting such reviews and is part of the process of identifying common reference standards for reporting them.\n\nResearch objectives\n\n1. To identify and review the methodological literature on the reporting of systematic reviews of health economic evaluations.\n\n2. To summarize and map methods, guidance, and recommendations for reporting such reviews.\n\n3. To identify and extract an initial dataset of candidate reporting items.\n\n\nMethod\n\nThe scoping review forms part of the larger PRISMA-EconEval project. The protocol for the scoping review follows the Preferred Reporting Items for Systematic Review and Meta -Analysis Protocols (PRISMA-P) 2015 Checklist,4 with the protocol and PRISMA-P checklist deposited on the Open Science Framework.5 We will report the scoping review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist.6\n\nThe scoping review will be conducted in various stages as shown in Figure 1 and will aim to identify an initial list of candidate reporting items. This initial list of reporting items will have generic relevance to systematic reviews of health economic evaluations regardless of the types of health economic evaluation (e.g., cost-minimization analysis, cost-benefit analysis, cost-effectiveness analysis, cost-utility analysis, cost-consequences analysis) and the vehicles for health economic evaluation (e.g., economic evaluations based on randomized controlled trials, economic evaluations based on observational studies with patient-level data, decision-analytic models) adopted by the individual studies they cover. Specific reporting items relevant to different categories of health economic evaluations may also be identified. The initial list will then be enhanced by findings from an additional sample of published systematic reviews of health economic evaluations. After refinement by the PRISMA-EconEval Management Group, this list will inform the multi-round online Delphi survey. Detailed plans for subsequent stages (post-scoping review) will be outlined in the comprehensive PRISMA-EconEval project protocol.\n\nThe scoping review will focus on two types of articles (either published in journals or elsewhere):\n\n• Methodological papers: Articles that describe methods, frameworks, guidance for conduct, or recommendations on the reporting of systematic reviews of health economic evaluations.\n\n• Enhanced case studies: Systematic reviews of health economic evaluations that include a minimum of two paragraphs that discuss methods, conceptual approaches, limitations (e.g., items not analyzed/reported in the review), and/or thorough categorization and reporting of health economic evaluation features that can inform the initial list of candidate reporting items.\n\nWe used the ECLIPSE Framework to help in framing the scope and objectives of the scoping review ( Table 1).7\n\nAugust 2024 – December 2024.\n\nWe will conduct searches in PubMed MEDLINE, Embase, and Web of Science for the period from 2015 to 2024. Relevant papers published prior to this timeframe will be identified through supplementary searching, reference checking and citation searching.\n\nFor the grey literature, we will identify and agree upon a list of 10-12 websites of health technology assessment agencies or health economics associations that may publish methods papers, guidance, and recommendations for reporting systematic reviews of health economic evaluations.\n\nAn experienced information specialist (ABo) will search databases of the published literature, applying guidance on filters at the intersection of “systematic reviews” and “economic evaluations” to develop and pilot our search strategies, including data sources, date limits, search terms, and syntax (Box 1).\n\n“systematic review of economic evaluations”[tiab:~0] OR “systematic review of cost effectiveness”[tiab:~0] OR “systematic review”[PT] AND (economic*[Ti] OR (“economic evaluation*” OR cost [Ti] OR costs [Ti] OR “cost effectiveness” OR “cost benefit analysis” OR “Cost Utility Analysis” OR “Cost-Benefit Analysis”)\n\n“systematic reviews of economic evaluations”[tiab:~0] OR “systematic reviews of cost effectiveness”[tiab:~0] OR ((“Systematic Reviews as Topic” OR “Review Literature As Topic”) AND (economics [SH] OR economic*[Ti] OR cost [Ti] OR costs [Ti] OR “cost effectiveness” OR “cost benefit analysis” OR “Cost utility Analysis” OR “Cost-Benefit Analysis”)) OR (“systematic reviews” AND (“economic evaluation*” OR cost [Ti] OR costs [Ti] OR “cost effectiveness” OR “cost benefit analysis” OR “Cost utility Analysis” OR “Cost-Benefit Analysis”) AND (Methods OR methodology OR methodological OR checklist* OR guideline*)) OR ((“Cost-Benefit Analysis” AND (Methods OR methodology OR methodological OR checklist* OR guideline*) AND (“Systematic Reviews as Topic” OR “Review Literature As Topic”))\n\nFor the grey literature, the scoping review team will search the websites of health technology assessment agencies and health economics associations, using similar search terms.\n\nRecognizing that methodological considerations are not always adequately reported in the titles and abstracts of systematic reviews of health economic evaluations, the research team will use innovative supplementary search methods to access the contents of full text articles and establish their eligibility for inclusion. Scite (open access alternative — Consensus) and Litsense will be interrogated for “systematic reviews of (health) economic evaluations”. Google Scholar will be searched using targeted search terms via the free open source Publish or Perish search tool to access full text contents of high currency and specificity. We will also use BASE,8 one of the largest search engines for academic web resources, which captures both academic and grey literature that may have been missed. Finally, a list of 10-12 known “index” items of high relevance to the review question will be used as the starting point for both backwards citation chaining (reference checking) and forwards citation chaining (citation chasing) using the Citation Chaser open-source tool.\n\nFor methodological papers, we will include articles that describe methods, frameworks, guidance, or recommendations on the reporting of systematic reviews of health economic evaluations. For enhanced case studies, we will include systematic reviews of health economic evaluations that contain at least two paragraphs critically discussing methods, conceptual approaches, limitations (e.g., items that were not reported but should have been), and/or thorough categorization and reporting of health economic evaluation features that can inform the initial list of candidate reporting items. Both types of articles published in English will be included without date restriction. We will exclude conference abstracts and proceedings, except for those that specifically focus on reporting methodologies of systematic reviews of health economic evaluations. For these, we will conduct additional searches and contact the authors (if necessary) to determine if a full-text publication is available. If a full-text version cannot be identified, they will be excluded.\n\nReferences for the articles retrieved will be uploaded to Covidence9 (open access alternative — Rayyan) for deduplication and initial screening (Phase One) and, subsequently, for full-text screening and reference management (Phase Two).\n\nThe eligibility of each identified study will be assessed by two of the five reviewers (ABa, ABo, JK, PT, SP) independently. A two-stage standard protocol will be developed and followed via checklists for each of the two phases. The checklists will be piloted on 100 random articles and screening criteria adapted accordingly.\n\nPhase One screening (Title and abstract screening): The following checklist will be used for the first screening of articles after deduplication ( Table 2). All articles will be classified accordingly. Each independently classified article by every two reviewers will be automatically compared by Covidence. Disagreements between reviewers will be resolved through consensus or by referral to a third reviewer.\n\nPhase Two screening (Full-text screening): For all articles classified as “Retained Phase 1”, the full article will be read and further classified as below ( Table 3). Disagreements between reviewers will be resolved through consensus or by referral to a third reviewer.\n\nData from studies that fulfill the inclusion criteria will be entered (by ABa, ABo, JK, PT, SP) onto an Excel form. Data to be extracted will include: article PMID number, title of paper, authors, year of publication, journal or source, type of literature (i.e., published scientific article, grey literature), and type of paper (i.e., methodological paper, enhanced case study). Recommendations from included studies on the methods and reporting of systematic reviews of health economic evaluations will be extracted and organized by codes and sub-codes. The coding will be conducted using NVivo V.1.710 (open access alternative — QualCoder). The reviewers will work together using a shared open codebook. All domains described in the included studies will be gathered and tabulated. Conventional sections and sub-sections of a systematic review as informed by the PRISMA guideline (i.e., title, abstract, introduction, methods, results, discussion, other information) will be used to inform the coding by which the identified themes and topics are organized. The extraction process will follow a pilot round of coding, continual refinement and revision of the codebook, and frequent consensus meetings.\n\nThe objective of the scoping review is to produce an initial list of recommended reporting items for systematic reviews of health economic evaluations, to be used in subsequent stages of the PRISMA-EconEval project. Where necessary, items will be renamed/rephrased, similar items will be combined, and items will be split if they cover two or more distinct topics.\n\nThe initial list of candidate reporting items identified by the PRISMA-EconEval Management Group will be arranged according to the conventional sections of a systematic review: title, abstract, introduction, methods, results, discussion, and other information. This structure broadly aligns with other extensions to the PRISMA reporting guidelines. The initial list of candidate reporting items will have generic relevance to systematic reviews regardless of the types of health economic evaluation or the vehicles for health economic evaluation adopted by the individual studies they cover. We will also include specific reporting items relevant to different categories of health economic evaluations in this and subsequent stages of the PRISMA-EconEval project.\n\nWe plan to disseminate the findings of the scoping review by submitting the resulting manuscript to a suitable peer-reviewed journal and presenting the key findings at the 2025 International Health Economics Association Congress. The initial list of candidate reporting items will be used in the subsequent stages of the project; i.e., review of sample papers and the Delphi surveys.\n\nThe protocol has been registered on the EQUATOR Network database11 and the Open Science Framework.5 The database searches have been conducted and pilot screening will soon take place.\n\nEthical approval is not required for this aspect of the PRISMA-EconEval project as it does not involve individual or personal data.\n\n\nAuthor contributions\n\nThe review was conceptualized collectively by the team (PT, JK, ABa, SP, ABo). PT developed the initial draft manuscript and created visualizations, with reviews and edits by the team. ABo and ABa provided expertise on the review methodology, databases and search strategy. PT was responsible for the revision and submission of the manuscript and is the guarantor of the protocol. SP, JK, ABo provided supervision throughout the entire process. All authors have reviewed and approved the final version of the manuscript.\n\nList of members of the PRISMA-EconEval Management Group\n\n1. Prof Stavros Petrou, Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom\n\n2. Dr Joseph Kwon, Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom\n\n3. Dr Phuong Bich Tran, Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom\n\n4. Prof Andrew Booth, Sheffield Centre for Health and Related Research (SCHARR), University of Sheffield, United Kingdom\n\n5. Dr Anastasios Bastounis, Sheffield Centre for Health and Related Research (SCHARR), University of Sheffield, United Kingdom\n\n6. Prof Sophie Staniszewska, RCN Research Institute, Warwick Medical School, University of Warwick, United Kingdom\n\n7. Mr Richard Grant, Patient and Public Involvement Representative, United Kingdom\n\n8. Prof Sally Hopewell, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom\n\n9. Dr Matthew Page, Methods in Evidence Synthesis Unit, School of Public Health and Preventive Medicine, Monash University, Australia",
"appendix": "Data availability\n\nNo underlying data is associated with this article.\n\nReporting guideline.\n\nOpen Science Framework. [Development of new reporting guidance for systematic reviews of health economic evaluations (PRISMA-EconEval)] DOI: https://doi.org/10.17605/OSF.IO/FSPG9.5\n\nThis project contains the following data:\n\n− PRISMA-EconEval Scoping Review Protocol.pdf\n\n− PRISMA-P-checklist.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nMoosapour H, Saeidifard F, Aalaa M, et al.: The rationale behind systematic reviews in clinical medicine: a conceptual framework. J. Diabetes Metab. Disord. 2021 Apr 8; 20(1): 919–929. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372: n71. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuhnen M, Prediger B, Neugebauer EAM, et al.: Systematic reviews of health economic evaluations: A structured analysis of characteristics and methods applied. Res. Synth. Methods. 2019 Jun; 10(2): 195–206. PubMed Abstract | Publisher Full Text\n\nShamseer L, Moher D, Clarke M, et al.: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2; 349: g7647. Publisher Full Text\n\nKwon J, Petrou S, Tran PB, et al.: Development of new reporting guidance for systematic reviews of health economic evaluations (PRISMA-EconEval). OSF. 2024 Jul 30 [cited 2024 Sep 26]. Publisher Full Text\n\nTricco AC, Lillie E, Zarin W, et al.: PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018 Oct 2; 169(7): 467–473. PubMed Abstract | Publisher Full Text\n\nWildridge V, Bell L: How CLIP became ECLIPSE: a mnemonic to assist in searching for health policy/management information. Health Inf. Libr. J. 2002 Jun 1; 19(2): 113–115. PubMed Abstract | Publisher Full Text\n\nBielefeld University Library: BASE - Bielefeld Academic Search Engine.[cited 2024 Oct 10]. Reference Source\n\nCovidence systematic review software. Melbourne, Australia: Veritas Health Innovation; 2024. Reference Source\n\nQSR International: NVIVO Release 1.7.2022. Reference Source\n\nEQUATOR Network: Reporting guidelines under development for systematic reviews.2024 [cited 2024 Oct 10]. Reference Source"
}
|
[
{
"id": "347340",
"date": "07 Jan 2025",
"name": "Ghislaine A.P.G. van Mastrigt",
"expertise": [
"Reviewer Expertise Health Economist",
"Methodologist",
"and Epidemiologist",
"in the field of systematic reviews of economic evaluations",
"quality asssessment and reporting of economic evaluations"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aims to investigate the existing literature through a scoping review to develop an alternative to the well-established PRISMA reporting guidelines, namely one to improve the reporting quality of health economic evaluations. Overall, this is a very well-written and clear protocol for performing this research. However, the authors were given a few suggestions to improve this scoping review protocol. Regarding the questions of the review report form:\nIs the rationale for, and objectives of, the study clearly described? Partly The authors report the three research objectives:\n1. To identify and review the methodological literature on reporting systematic reviews of health economic evaluations. 2. To summarize and map methods, guidance, and recommendations for reporting such reviews. 3. To identify and extract an initial dataset of candidate reporting items.\nFor objective 1, I would not solely focus on ‘reporting’ whether you can identify all the relevant literature; I would rephrase it as follows: To identify and review the methodological literature of systematic reviews of health economic evaluations to improve the reporting quality of these studies. For objective 2: it would rephrase it as follows: To summarize and map methods, guidance, and recommendations for methodological literature of systematic reviews of health economic evaluations. For objective 3: to identify and extract an initial dataset of candidate items to develop an extension to PRISMA guidelines for Health economic evaluations\nIn summary, what aspects do you consider as part of reporting economic evaluations? This could be specified for the objectives, but this is also needed for the protocol.\nIs the study design appropriate for the research question? Yes The authors propose a scoping review to investigate the existing literature on this topic, I agree this is an appropriate research design to investigate this research question.\nAre sufficient details of the methods provided to allow replication by others? Partly Regarding the step of the selection of the databases: They state: ‘’ We will conduct searches in PubMed MEDLINE, Embase, and Web of Science for the period from 2015 to 2024’’. However, no rationale behind the choices of these bibliographic databases is given; for economic topics; Econlit could also be a relevant database to check.\nOther topics General topic: study designs For the scoping review but also the PRISMA-EE development; what kind of types of economic evidence do the authors want to cover in their reporting guidelines? only full economic evaluations: like cost-utility or cost-effectiveness analyses or also partial economic evaluations like; cost of illness studies, resource use etc. This is explained in the phase one checklist but should also be more clearly mentioned in the protocol. It is highly recommended to start the study after the registration of the protocol; so please adapt the start date of review to January 2025. Sections: search strategy/search terms and strings\nThis section could be improved by adding additional information on search strategy development and databases selected (for details see comments below). It is highly recommended to report the search strings for each of the bibliographic databases which will be used to identify relevant studies. In addition, it is also highly recommended to use validated and predefined search strings as much as possible. The ISSG website is a recommended source to look for, especially for the economic topics (table needs further specification). Furthermore, more details could be given on how the search strategies were developed. For this the Prisma extension ‘’PRESS’’ is very helpful. The search strategies listed in box 1 do not match the study objectives and could be made more specific. Details of the 10-12 websites of health technology assessment agencies or health economics associations could be added in an appendix. Please also specify the 10-12 ‘’index items’’ mentioned to be used as starting points for backward and forward citation chasing. ‘’Citation chasing’’ is mentioned twice, once briefly at the beginning of the section and more detail at the end, one of them could be deleted. Section: Inclusion and exclusion criteria Details regarding the type of economic evaluation included, approaches used (e.g. model/trial-based), as well as including full or also partial economic evaluations should be mentioned in the list of eligibility criteria. Section: Article screening and selection Will you use Ryan or Covidence to handle the study results? In the sentence: ‘’The checklists will be piloted on 100 random articles and screening criteria adapted accordingly’’. You could mention that you use two separate checklists for screening and selection. Add a sentence on the approach you will use to contact authors to obtain full-text papers if only abstracts are available. Section: data extraction and coding Will you use NVivo V.1.710 or QualCoder for coding? A draft of the data extraction sheets could be added to the protocol. In addition a list of example general or specific candidate items? What do you mean by the last part of this sentence: ‘’We will also include specific reporting items relevant to different categories of health economic evaluations in this and subsequent stages of the PRISMA-EconEval project’’? Could you please explain it?\nAre the datasets presented in a usable and accessible format? Not applicable\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1382
|
https://f1000research.com/articles/13-1381/v1
|
18 Nov 24
|
{
"type": "Review",
"title": "Youth athletes and wearable technology",
"authors": [
"Joon-Hyuk Park",
"Chitra Banarjee",
"Jirui Fu",
"Cynthia White-Williams",
"Rachel Coel",
"Tracy Zaslow",
"Holly Benjamin",
"Florianne Silva",
"Rock Vomer",
"George Pujalte",
"Joon-Hyuk Park",
"Chitra Banarjee",
"Jirui Fu",
"Cynthia White-Williams",
"Rachel Coel",
"Tracy Zaslow",
"Holly Benjamin",
"Florianne Silva",
"Rock Vomer"
],
"abstract": "Wearable sensors have become integral tools for monitoring biomechanical and physiologic aspects of athletic training and performance. A prominent trend in fitness technology, wearable devices now measure a variety of health characteristics, including movement and posture, physiologic measures (eg, heart rate and energy expenditure), and fluid and electrolyte losses, to understand an athlete’s physiologic responses during activity. Sleep has proven integral to athletic performance, and sleep monitoring wearable devices (eg, watches, rings, and headbands) use various measures, such as actigraphy and pulse oximetry, to analyze sleep quality. Young athletes benefit from wearable devices during training sessions, where multimodal data are collected and analyzed to assess performance. Wearable devices are also useful for resistance training, biofeedback, and electrical muscle stimulation, providing athletes with tools to optimize their training regimens. Moreover, these devices play a crucial role in athlete safety by monitoring cardiac physiology, head impacts, and muscle rehabilitation after injury. We provide a comprehensive review of current wearable technology and its application in youth athletics, describe where and how these sensors are used to help enhance physiologic, biomechanical, and performance parameters, and discuss future directions for wearable devices to advance sports science and athlete management.",
"keywords": [
"athletic performance",
"athletic training",
"sensors",
"wearables",
"youth athletes"
],
"content": "What wearable technology can do\n\nWearable devices are typically small, sensor-based, and worn on the skin to enable monitoring of biomechanical and physiologic characteristics, which benefits athletes by informing training and performance and reducing injury. These devices include a wide range of technology, including electrocardiography (ECG), electromyography (EMG), electroencephalography-based brain sensing platforms, and microelectromechanical systems (MEMSs). The American College of Sports Medicine has identified wearable technology as the top trending fitness technology for 4 of the past 5 years.1–4 The rapid growth of wearable devices can be attributed to their use as both wellness and medical devices, monitoring parameters that describe general well-being and detect medical abnormalities.5 This dual use in fitness and health has presented potential for wearable devices in the young athlete population, where they have been used to track activity,6 monitor cardiovascular health,7,8 and identify sleep trends9 and as a tool for training10,11 and real-time performance feedback12 ( Figure 1). Here, we explore the current applications of wearable devices in the training of young athletes.\n\nMovement and physical activity tracking\n\nThe most common use for wearable devices in sports is to monitor movement and physical activity. Some of the earliest activity monitors were movement sensors for detecting step count, including pedometers, accelerometers, and global positioning system (GPS) devices.8,13 With pedometers, steps are counted when the vertical acceleration of a spring-loaded lever arm passes a designated force sensitivity threshold.14 Similarly, accelerometers and gyrometers are MEMSs that detect changes in capacitance based on the vibration and rotation of a mass between 2 electrodes to calculate step counts.15 Step count can then be used to derive other measures of importance to young athlete across a variety of sports, from tracking gait velocity in runners,16,17 to monitoring stair running in resistance trainers,18 to recording calories expended in endurance athletes.19,20 GPS and ultrawideband devices function differently in that they transmit signals from satellites to determine speed and position.21 By using anchor-based techniques for tracking, GPS is more appropriate for athlete tracking than MEMS devices, which rely on abrupt motion for tracking.22 Some sports applications of GPS devices include monitoring sprint running performance23 and determining the distance covered by golfers.24\n\nHeart rate and heart rate variability monitoring\n\nMonitoring heart rate (HR) is important for determining the intensity of training for athletes and detecting overtraining to prevent injury.25–27 Wearable HR monitors primarily consist of chest-worn straps with sensors placed on the sternum or wrist-worn devices. While wrist-worn devices have become popular with endurance athletes, a recent study showed that chest-worn devices are more accurate than wrist-worn when compared to ECG, the criterion standard in medical settings. Wrist-worn devices use optical plethysmography, which shines light onto the skin and determines HR by visualizing oscillating blood volume.27 Movement causes HR to rise due to increased demand for oxygen transport and carbon dioxide removal; as athletes exert themselves, their HR continues to rise until it reaches an individual-specific maximum HR.28 Over time, this causes changes in the heart structure, leading to athlete’s heart, which is characterized by hypertrophied left ventricular walls and reduced resting HR. HR monitors can be used to assess these changes to determine if evaluation by a medical professional is required.29 Additionally, HR monitors can be used to estimate energy expenditure (EE) to a relatively high degree of accuracy.30\n\nWearable devices can also be used to monitor HR variability (HRV), which is especially useful for endurance athletes who have greater HRV than the general population.31 While the criterion standard for HRV monitoring is ECG, wearable devices incorporating photoplethysmography sensors have also been used for this purpose.32 Because HRV is a marker of the autonomic nervous system and its responses to both external and internal stimuli, it is an important tool for evaluating training load. HRV can also determine the presence of respiratory sinus arrhythmia, a cardiopulmonary condition to which athletes are particularly susceptible and during which respiration interferes with variations between R waves on ECG.33\n\nOther advances in HR monitors involve the incorporation of wearable devices into common personal items. This includes the development of smart clothing, which integrates electrodes and sensors into wearable clothing material,34 devices worn on the ear in the form of headphones,35 and epidermal patches placed directly on the skin.36 These devices demonstrate the potential for engineering advances in health monitoring as they become less invasive, more common, and more innovative.\n\nEnergy expenditure\n\nEE consists of 3 parts: 1) basal EE, the energy required to maintain body functioning at rest; 2) diet-induced thermogenesis, the energy from breaking down food products; and 3) activity EE, the energy required for physical activity. Tracking activity EE in athletes is important in evaluating sufficient caloric intake levels and determining training load and seasonal planning.37,38 The criterion standard for monitoring EE is indirect calorimetry, which works by recording oxygen consumption and carbon dioxide release at regular intervals, typically breath-by-breath.39 Wearable devices to estimate EE often use a combination of measures, including movement trackers (eg, accelerometers), physiologic monitors (e.g., HR monitors), galvanic skin response, heat flux, and ambient temperature.38,40 However, EE trackers are limited as they are based on algorithms validated on resting adults, and as such, have been shown to underestimate EE during physical exertion by athletes, particularly youth athletes.38\n\nSweat sensing\n\nMost wearable devices that focus on monitoring sweat use microfluidic biosensors and chemical assays to provide visual feedback to the user. A range of parameters are commonly monitored in sweat devices, including sweat rate, concentrations of compounds (eg, chloride, calcium, ammonium, and lactate), and pH levels. Sweat patches monitor sweat rate and chloride concentration to inform athletes about appropriate hydration based on their level of water loss.41,42 Other devices monitor calcium and ammonium levels in sweat to assess bone and liver function and inform trainers and coaches about the use of potential nutritional supplements or vitamins.43 Another variable commonly measured by sweat monitoring is lactate concentration using enzyme biosensors.44,45 As a product of metabolism during exercise, lactate is linearly related to sweat rate and can determine lactate anaerobic threshold, an abrupt increase in lactate concentrations due to an inability to clear lactate as fast as it is being produced. This threshold is of particular importance for endurance athletes as a predictor of their running performance and velocity.46\n\nSleep monitoring\n\nWearable sleep monitors come in many forms, including watches, rings, and headbands,47 most of which use measures such as actigraphy, pulse oximetry, HRV monitoring, and skin temperature.9 Actigraphy is the integration of sleep diaries with accelerometers; however, they have been shown to significantly overestimate sleep variables due to low specificity when compared to the criterion standard of polysomnography.48 Pulse oximetry, a measurement of oxygen concentration in the blood, adds a layer of improvement in monitoring sleep efficiency and estimating stages of sleep. The most accurate wearable sleep monitors use a combination of actigraphy, pulse oximetry, and electroencephalographic sensors.49,50\n\nMaintaining healthy sleep cycles is critical for young athletes, as sleep-related metabolic, hormonal, and immunologic functions allow for exercise recovery, improved performance, better mental health, muscle repair, bone growth, and production of cytokines to promote immune function.51,52 Additionally, monitoring sleep parameters, such as total sleep time, sleep efficiency, and wakefulness after sleep onset, can reveal poor sleep hygiene and sleep disturbances, including sleep apnea and insomnia, found to be more common in young athletes.53 However, these devices have considerable room for improvement, as evidenced by consistently high sensitivity and low specificity, resulting in overestimation of total sleep time and sleep efficiency and underestimation of wakefulness after sleep onset by most commercial sleep monitors.48\n\nWearable devices have been widely used to enhance the performance of young athletes during routine training ( Figure 2). The purpose of performance-enhancing wearable devices for athletes is categorized as training monitoring and assessment, resistance training, biofeedback, muscle stimulation, and athletic motivation.\n\nTraining monitoring and assessment\n\nTraining monitoring and assessment systems within wearable devices use the wearable sensor to collect dynamic and biologic data from athletes during training.40,54 Most existing technology uses wearable inertial measurement unit (IMU) or force sensors to measure the joint angles, accelerations, and interaction forces of young athletes. These devices then use data analysis methods and classification-based machine learning (ML) algorithms to assess performance during the training session.55–60 This information can be used to improve efficiency and output and correct biomechanics to reduce risk of injury. For example, Wang et al58 used a wearable IMU sensor and a classifier-based ML algorithm to track and measure human motor skills in hammer-throw training to help coaches assess athletes’ mechanics, strengths, and areas of improvement. Yi and Yu59 implemented a similar approach to track biomechanics in motion during Wushu training (a martial art originating in China). In their study, measurements from the wearable IMU sensor were processed by a Kalman filter to estimate the acceleration of athletes, then principal component analysis and linear discriminate analysis algorithms classified the measured data into specific Wushu motion.59 McGrath et al56 compared various types of ML algorithms to identify overtraining in fast bowling by using dynamic data collected from a wearable IMU sensor. Four types of ML algorithms—random forest, support vector machine, gradient boosting, and neural networks—were used to detect overtraining, and the accuracy of each algorithm was determined based on the classification performance. When the algorithms were compared, the support vector machine had the best accuracy in the detection of overtraining.56\n\nThe above-mentioned research used laboratory wearable sensory systems to track the kinematics of athletes using equipment that is not designed to be worn for prolonged periods of time. To improve the ergonomics of wearable sensors for tracking performance, Lu et al55 developed a stable and durable triboelectric nanogenerator to track the loading level of athletes during training. Their sensor uses MEMS technology, allowing it to be smaller and more ergonomic than other similar sensors.55\n\nSkazalski et al57 demonstrated the validity and reliability of a commercially-used wearable sensor, VERT (Mayfonk Athletic, LLC), to track jump-specific training and competition load in elite volleyball players. VERT tracked the training jump height of volleyball players, then evaluated competition load with respect to the measured jump height. To validate VERT, the competition load measured by the sensor was compared to the load measured by a laboratory wearable sensor. Their results demonstrated the accuracy and validity of the sensor in the training of professional volleyball athletes.57\n\nInstead of wearable IMU and force sensors, Tahla61 used a wearable graphical motion tracking system. Athletes were required to wear a motion tracker while an image-capturing system collected images and incorporated image processing methods, such as computer vision and deep neural network, to detect the motion of athletes. Unlike wearable IMU and force sensors, the wearable graphical motion tracking system requires simultaneous use of an external image-capturing system, which makes it only available in a laboratory environment.61\n\nIn addition to dynamic data, such as angular acceleration of an athlete’s joint, physiologic parameters, such as HR and EMG, can also be used to monitor and assess the performance of young athletes.62–67 Compared to performance monitoring and assessment systems that collect dynamic data, devices that collect biologic data focus on interpreting the intensity and effect of an athlete’s exercise session. For example, Zhu et al67 used a wearable ECG sensor to monitor HR of athletes and quantified training intensity during different physical activities. The detected training intensity can optimize coaching of athletes by targeting HR range.67 Training intensity can also be monitored by other types of biologic signals.63,66 For example, Orucu and Selek63 used surface EMG sensors to measure the level of muscle activation from agonistic muscles of athletes. The measured EMG signal was compared to the maximum voluntary contraction to determine the ideal level of training intensity for individual athletes.63 Yogev et al66 used a wearable muscle oxygenation sensor to measure the exercise intensity of cyclists.\n\nResistance training\n\nWearable devices can also improve the performance of young athletes during resistance training. In contrast to wearable devices designed for evaluation of cardiovascular training, wearable resistance training devices involve attaching an external load onto the lower or upper limb of athletes, depending on the type of sport. However, few researchers have investigated wearable resistance training devices for improving the performance of athletes.10,68,69 Feser et al10 and Bustos et al68 investigated the effects of lower limb wearable resistance devices on the training performance of soccer and rugby athletes, respectively, and demonstrated the efficacy of the devices to improve training performance. Kadhim et al69 developed a variable resistance suit for both upper- and lower-limb resistance training, designed to modulate tunable, bidirectional, and speed-dependent resistance at the elbow and knee joints.\n\nBiofeedback\n\nWearable devices can also be used to provide biofeedback to the young athlete. Traditionally, feedback from coaches and trainers occurred via subjective observation; however, wearable devices allow cost-effective quantification of biomechanical variables to enhance performance and aid training.70,71 Wearable devices can provide biofeedback by collecting and storing data or providing real-time feedback on variables such as joint load and balance performance.72,73 In collecting biometric data, these devices can inform users about the chance of injury when load or balance exceeds specific thresholds or when improper biomechanics threaten joint stability. Additionally, wearable devices can integrate haptic components, which provide vibrotactile feedback to athletes to change training intensity or correct movement patterns or timing. For example, sensorized insoles with haptic feedback are used to aid soccer players in improving sprint performance.74 Other biofeedback sensors use real-time ultrasonography to improve muscle contraction training in bodyweight and weight training by sending images to an external device (eg, smartphone) through an app to help athletes visualize the activation of their muscles.75 In addition to biomechanical improvements, wearable devices can be used to provide biofeedback to improve stress management, maintain hydration status, and regulate sedentary activity.76–78\n\nMuscle stimulation\n\nElectrical muscle stimulation, which uses electrical impulses to contract targeted muscles, is another application of wearable devices to modulate the behavior of young athletes. Electrical muscle stimulation is used for training purposes to aid coaches in guiding athletes to learn correct muscles to engage at the right time, thereby enhancing muscle coordination and mitigating injuries.79,80 The wearable devices used for electrical muscle stimulation include IMUs, EMG sensors, microprocessors, motors, and actuators.81–83 IMUs are used to monitor sports activity and exertion by stimulating vibrotactile or electrotactile bands and informing the athlete of abnormal movement or overexertion.81 EMGs are similarly used to monitor muscle contraction and activation while also monitoring for fatigue, both of which can guide an athlete’s training.79 Microprocessors are used to communicate with software involving vibrating motors and actuators that provide vibrotactile and electrotactile feedback, respectively.84,85 While most of these devices are wrist-worn smart bands, some apply transcranial direct current stimulation, where a small current (2-3 A) is delivered over the head to target the motor cortex.86 A study using this method with wearable technology headphones found that the feedback improved power output and accuracy during spring cycling.87\n\nAthletic motivation\n\nAnother aspect of wearable devices is the functionality of social motivation through the shared use of these devices in team sports. Applications that encourage sharing of workout session data with others have been shown to promote social networks to improve adherence to training.88,89 This is especially beneficial for adolescent athletes, who are forming their identity in sports. High school athletes with wearable devices were found to be more likely to indicate a desire to pursue professional sports in the future.90 Wearable devices can also provide motivation through reminders to maintain the frequency of training and provide statistics on training intensity and chance of injury.91\n\nApproximately 30 million children and teenagers engage in organized sports, resulting in over 3.5 million sports-related injuries each year among young athletes.92,93 To successfully return to competition, the guidance of a therapist-led rehabilitation program is imperative. This rehabilitation process involves various stages, including diagnosis, inflammation management, promotion of healing, fitness enhancement, and injury prevention.94 Consequently, recovery from sports-related injuries demands a considerable amount of time and effort. Because of the increasing number of sports-related injuries and the extended amount of effort required for rehabilitation, the US is experiencing a shortage of rehabilitation therapists.\n\nAn alternative to traditional rehabilitation with a professional therapist, exoskeletons and exosuits are a subcategory of wearable devices designed to provide controlled force or motion to help in physical rehabilitation of various conditions, including recovery and rehabilitation from injuries in athletes.95,96 Compared to conventional rehabilitation therapy that relies on the instruction and assistance of a therapist, rehabilitation with wearable exoskeletons or exosuits alleviates the human workload, allowing repeatable and longer rehabilitation sessions for the patient while providing a means to assess the progression of rehabilitation outcomes through integrated sensors.97 A few studies have demonstrated the applicability and effectiveness of using wearable devices in athlete rehabilitation98–101; however, due to high cost and inaccessibility, the use of these devices for rehabilitation of sports-related injuries in young athletes is limited.\n\n\nTraining and performance enhancement\n\nWearable technology can monitor athletes’ performance and inform their training regimens. These devices provide feedback on physical stress, which can be used to balance resistance training and endurance programs.102 Information such as HR, HRV, distance, and sweat can help athletes optimize training. These measures are tracked using a combination of position sensors such as GPS, global navigation satellite system, ultrawideband, inertial sensors, and accelerometers.102\n\nGPS can track the pace and location of competitors in numerous sports, including football, orienteering, cross-country skiing, and field hockey. Using GPS, athletes gain information about speed and position parameters.103 In rugby, a high-intensity sport characterized by rucking, sprinting, scrummaging, and tackling, GPS has been used to investigate collisions (changes in a player’s momentum brought on by contact with another player), impact forces, and physiologic demand.15,104 Some players are more prone to collisions due to their position on the field. GPS can quantify the number of collisions and intensity of contacts by position and player to inform tackling profiles and relative risk of injury.104 For example, in rugby, different positions demand different skills and strengths; hence, data such as distance traveled, pace, calorie expenditure, HR, locomotor activity, load, and speed can assist players and coaches in developing position-based training.104,105 Athletes can receive maximum training benefits when the training stimulus aligns with the physical demands of the sport.105\n\nWhile GPS visualizes the field of play and provides feedback on speed and distance, it does not measure biomechanics. However, biomechanical parameters can be measured by IMU sensors.106 These sensors measure impact accelerations and multiple angles of movement with a mechanical movement-sensing device that can track movement patterns and mechanics in multiple dimensions.15,107–109 Major components of IMUs include accelerometers, gyroscopes, and magnetometers.110 IMU-based devices measure movements such as jump height, impact force, trunk rotation, and joint position.111 For example, IMUs can be used in sprinters to measure stance durations that contribute to running speed.15 In swimmers, triaxial accelerometers and gyroscopes provide data related to stroke technique, racing performance, and energy consumption. By examining the signals from IMU devices and comparing them to video recordings, biomechanical and training changes can be made that may lead to reduced risk of injury and improved athletic performance. Accelerometers can also be used to assess energy consumption using vertical integration, an essential factor in determining a training regimen’s intensity.15\n\nIMU devices with gyroscopes can measure velocity around a fixed axis.110 These devices have been used to optimize velocity-based resistance training in overhead movements to improve mean power propulsion among volleyball athletes.112 Optimizing velocity-based strength training while minimizing injury is critical to elite-level volleyball and general sports performance.\n\nMagnetometers are typically used with accelerometers and gyroscopes to filter the orientation of movements.110,113 In individual sports, such as sprinting and skiing, athletes’ speed and timing influence their success. Magnetometers can help determine these minute changes by using anisotropic magnetoresistive technology, which uses gravitational forces to measure movements in athletes along all 3 axes (x, y, and z).110,114\n\nUsing wearable IMU devices, including accelerometers, gyroscopes, and magnetometers, swimmers gain information on acceleration, angular velocity, magnetic field, and attitude angle.115 This information can be used at the macro level to identify the total quantity of swimming (eg, number of laps) and at a micro level to identify the swimming phases in each lap that can aid in development of a swimmer’s training strategy.\n\nIMUs can overcome the limitations of GPS-based measurements as they offer an external load estimate of physical activity. This measurement represents all stress placed on the body due to acceleration, deceleration, direction changes, collisions, and foot strikes. These load measurements can be taken indoors or in locations with low signal quality, unlike GPS measurements, which depend on satellite signal strength.116 A combination of GPS and IMUs in wearable technology can track the position and orientation of players.110 For example, a swimmer’s speed at the midway point and the number of strokes for each trial can be calculated using GPS and IMU data. This combination has been shown to accurately record swimmers’ velocity with freestyle, breast, and butterfly strokes, helping them precisely measure strokes to enhance their performance.117,118\n\n\nAthletic injury reduction and prevention\n\nAthletic groups are constantly looking to reduce injuries while advancing player development. Wearable technology can help reduce injuries by informing a balanced training and recovery regimen.119 Data such as HR provided by wearable technology is a good indicator of athletes’ training and rest capacity.120 Information such as hydration status, sleep, and cardiac health can inform training and return-to-play protocols after injury.121\n\nData from wearable devices can inform injury prevention by optimizing athlete workloads.109 It is possible to determine an athlete’s internal and external workload during a training session using parameters captured by wearable sensors. External workload is an objective indicator of the external stress placed on the body, which is essential to evaluate the efficacy of a training program and reduce risk of injury. Accelerometers and GPS measure distance, velocity, duration, and training frequency; this information informs external workload.116,122 A study determining the impact detection rate in American football found 96% validity for 2 wearable sensors: a helmet system with 6 linear accelerometers and a mouthguard system with a 3-axis linear accelerometer and a 3-axis angular rate sensor to track concussions by detecting linear and angular head accelerations (external workloads) at impact.123\n\nInternal workload includes physiologic and mental stress experienced by athletes during training and competitions.116 Managing internal workload enables tailoring of training exercises and detection of potential health hazards, burnout, and dysfunction. Wearable technology, including chest belts and photoplethysmography, can monitor internal workload indicators (eg, HR, HRV, and temperature monitoring) to measure changes in the body in reaction to external workload.122,124 Abnormal HR or rise in body temperature can indicate an athlete’s inability to cope with training intensity; this information can be used to modify the workout with adequate recovery.125 The acute-to-chronic workload ratio, a measure of how hard an athlete is training and their willingness to take on greater athletic demands, can be determined by developing the athlete’s workload profile using both external and internal workloads.121 A study determining the relationship between workload and risk of injury in young football players using GPS and accelerometer sensors suggested that noncontact injury was linked to higher acute workload. Gradual increases in chronic activity may help athletes improve their physical stamina for greater acute workload and injury resistance.126\n\nSleep is vital for athletic recovery, muscle repair, and adaptation following training. It also improves performance and mitigates injury.127 Wearable sleep sensors use actigraphy to track movement, HR, and HRV as indications of sleep-wake cycles.120,127 Athletes in high-intensity aerobic sports, such as cycling and swimming, who endure large amounts of psychological and physical stress, can use these devices to balance resistance-training programs with sleep hygiene, allowing for adequate rest and recovery.122\n\nHydration levels can provide insight into athletes’ physiologic state. Increased feeling of exertion, lower aerobic capacity, impaired cognitive function, and poor physical performance are associated with fluid losses above 2% of body weight in athletes.128 One study developed dehydration self-monitoring technology that can instantaneously determine the hydration status of human skin with wearable electrodermal activity sensors combined with signal processing and ML methods.129 This wearable technology can track hydration levels with 84.5% accuracy, send signals to a smart device in real-time, and immediately notice when a dangerous threshold is crossed.129 Another study used cardiovascular response to orthostatic postural shifts to develop a noninvasive wearable technology implanted with ECG leads and IMUs for measuring dehydration in athletes.128 The study suggested that wearable technology can detect at least 2% body weight loss from dehydration by using the connection between hydration and cardiovascular reactions to orthostatic changes.128\n\nIn athletes, frequent sharp change-of-direction occurrences may cause neuromuscular and musculoskeletal fatigue, increasing the risk of musculoskeletal injury.109 IMU data have demonstrated a relationship between acceleration load and frequency of overexertion injuries in athletes in contact sports such as American football, Australian football, and rugby.120 IMUs are placed on the body to track the players’ movements on the field surface. These movement patterns can assess risk factors, such as position, load, and level of play, that can help athletes correct improper biomechanics to better tolerate external stress from impacts that may otherwise result in injuries.120 While motion-capture camera systems can also be used to detect change of direction, with numerous businesses now providing comparable solutions, wearable technology is emerging as a preferable alternative to camera-based athlete tracking systems due to their versatility, ease of use, and unrestricted data collection space.109\n\nWearable technology can assist both recreational and elite athletes in improving their performance and ensuring their safety by monitoring cardiac physiology and pathology. A combination of ML and photoplethysmography in wearable technology can be used to identify patients with obstructive hypertrophic cardiomyopathy.130 The optical sensor in these devices records pulse wave traces, detecting changes in blood volume at the skin surface. Additionally, wearable technology can track cardiac rhythms, which can help detect atrial fibrillation.131,132 Wearable technology with ECG capability has been shown to detect atrial fibrillation with the same accuracy as 12-lead ECG machines.133\n\nWearable technology can provide feedback to monitor biochemical indicators of muscle metabolism, oxygenation, and blood flow to provide insight into muscle rehabilitation. Near-infrared spectroscopy is used to gauge the oxygenation of living muscles.116 Wearable sensors with near-infrared spectroscopy can measure athletes’ muscle oxygen saturation levels and provide feedback on muscle recovery. These sensors can also continuously measure change in oxygen saturation of muscle tissue to assess a player’s capacity to maintain performance while avoiding fatigue during workouts.134 A study compared changes in muscle oxygenation levels in club-level swimmers and triathletes during a 200-m swim using wearable near-infrared spectroscopy sensors,135 and found that the swimmers displayed no significant change in tissue saturation index in the upper and lower body (P=.686). In contrast, the triathletes experienced a significant reduction in tissue saturation index in the upper body compared to the lower (P=.043), suggesting that triathletes predominantly use the upper body for propulsion during the same exercise.135 Another study used wearable near-infrared spectroscopy sensors to determine muscle tissue oxidative capacity and recovery time in intermediate, advanced, and elite rock climbers.136 The study indicated that oxygen recovery per second in the elite group was significantly higher than that in the intermediate and advanced groups (flexor digitorum profundus: 4.2 vs 0.7 and 0.3; flexor carpi radialis: 4.8 vs 0.1 and 0.2, respectively); therefore, the elite group required less time to half recovery than the control and intermediate groups.136\n\n\nFuture directions of wearable technology in sports\n\nMany recent studies of wearable technology use ML and deep learning (DL) models to detect unsafe movement patterns, changes in balance, and abnormal heart rhythms to decrease the risk of injury.137–140 These studies demonstrate the potential of advanced computational algorithms, such as convolutional neural networks, recurrent neural networks, and long short-term networks, in assessing physical performance and preventing injury. However, studies of this nature are scarce as most wearable devices have limited computational power to run ML/DL models. A benefit of using ML/DL is the ability to identify patterns that are difficult for coaches, athletic trainers, and personal trainers to monitor, including sleep and movement patterns. For example, Zhang et al141 described the use of multilevel feature learning and recurrent neural networks on data collected from a wrist-worn wearable device to classify stages of sleep. Jacobson et al142 also demonstrated the application of a multilayered ensemble DL model in adolescents to predict anxiety based on sleep pattern data from wearable devices. However, despite proven uses in monitoring sleep patterns, this methodology has not been investigated in improving health outcomes for young athletes.\n\nMovement pattern data may also benefit from the application of ML/DL tools, but more research related to use in athletic training is needed. While Arciniega-Rocha et al143 and Jiang and Zhang144 have shown the use of DL to identify correct stances in the training of athletes, research on the application of ML/DL to develop training plans that optimize learning is limited. Tracking athletic progress with a more detailed perspective can help construct individualized training plans that reduce the risk of injury and maximize learning speed.\n\nMany recent wearable devices have integrated multiple sensors to increase the number of measurable variables. This design improvement provides more comprehensive information regarding an athlete’s physiologic, biomechanical, and performance parameters for use by athletes, coaches, trainers, and health care personnel. For example, Fuss et al145 investigated pressure-sensitive boots to monitor the training load of kicking in soccer players. The researchers identified an optimal type of foot support to maximize the chances of scoring a goal. Similarly, accelerometers can be placed at particular parts of the body to monitor movement speed, direction, and explosive effort, as well as assess injury risk in sports such as volleyball.113 However, there is a lack of research comparing these parameters and their relevance and implications for young athletes in a variety of sports environments. Some wearable devices may be particularly helpful for all young athletes, such as HRV monitors which may assist in the detection of cardiac malformations and arrhythmogenic conditions and may alert coaches and parents when young athletes need to seek medical care.32 Particularly for young athletes participating in endurance sports, HRV monitoring may be of critical importance to early diagnosis of cardiopulmonary conditions such as respiratory sinus arrhythmia. Further interdisciplinary collaborative research is needed to determine the parameters and viable wearable sensor options necessary to improve youth athlete performance and safety.\n\nWearable exoskeletons and exosuits have been used for rehabilitation and training. As highlighted above, these wearable technologies have proven valuable in reducing human labor while improving repeatability and effectiveness of physical therapy. Swank et al146 demonstrated the benefits of wearable exoskeletons in the rehabilitation of patients with spinal cord injuries, while Longatelli et al147 and Shapkova et al148 used exoskeletons to aid patients with stroke or paralysis in regaining their motor capabilities. Additionally, Schnieders et al149 and Proud et al150 successfully implemented exoskeletons in military personnel training for manual handling and operation of firearms. Further research is needed to explore and understand the potential implementation of exoskeleton and exosuit technologies in athletic training.\n\nIn the multifaceted realm of training and rehabilitation, an intriguing parallel emerges when comparing the application of exoskeletons for athletes and nonathletes. Exoskeletons, primarily conceived for regimented applications, exhibit an adaptability that traverses diverse user groups. Exoskeletons have a control system that relies on wearable sensors, such as IMU150 or EMG sensors,151 that detect the user’s body joint angular displacement or velocity, or the force produced by muscles. This meticulously designed assistive mechanism helps the user along a trajectory of predefined motions or compensates for the gravitational forces experienced by the user. For patients with limited motor functions, exoskeletons can discern their motion intentions through a number of sensors,95,152,153 gently guiding their movements toward a goal and improving the dexterity of their impaired limbs. Likewise, athletes may be able use exoskeletons to improve agility, power, and endurance, while avoiding movement patterns that risk injury. The applications of exoskeletons in athletic training should embrace a holistic and nuanced evaluation of the performance of athletes, leveraging several state-of-the-art wearable sensors, including IMUs,154 EMG,63 and ECG.155 Data collected by the wearable sensors will quantify athletic performance, allowing the exoskeleton’s training strategies to be adjusted to improve training outcomes. Rehabilitative exoskeletons, therefore, may be viewed as both movement facilitators and ambitious trainers. The process of helping athletes recover to preinjury ability is collaborative work, with the exoskeleton and an ensemble of wearable sensors playing pivotal roles, echoing the data collected from wearable sensors.6 The application of exoskeletons for athletes for training and rehabilitation, therefore, is an extension of the application of wearable sensors.\n\n\nConclusion\n\nWe reviewed wearable technology and its potential for enhancing training, performance, and injury prevention in young athletes. Wearable devices serve versatile roles as training monitors, aids, and biofeedback tools in athletic training. GPS devices play a crucial role in monitoring diverse sports activities, from sprinting to golf distances, while HR monitors are used to track HR and estimate EE. Ongoing innovations focusing on more accessible, less expensive, and less invasive designs demonstrate notable progress in health monitoring. ML, particularly the support vector machine, shows promise in detecting overtraining. Biologic signals, such as surface EMG and muscle oxygenation monitor training intensity and effectively enhance athletic performance. These wearable devices also contribute to stress management, sleep, cardiac health, and hydration regulation to provide comprehensive information aligning training stimuli with sports demands. Also, biomechanics during changes in direction can be analyzed using wearable sensors for injury prevention, track cardiac rhythms, and identify conditions like atrial fibrillation. Challenges exist, such as the underestimation of EE during physical exertion in young athletes. At present, some forms of wearable technology are limited to investigational laboratory settings. Collaboration among coaches, trainers, athletes, and medical personnel is crucial for refining parameters and selecting viable wearable sensor options. The evolving landscape of wearable technology holds promising opportunities for personalized training plans and improved outcomes for young athletes.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nAcknowledgment\n\nThe Scientific Publications staff at Mayo Clinic provided copyediting, proofreading, administrative, and clerical support.\n\n\nReferences\n\nThompson WR: Worldwide Survey of Fitness Trends for 2019. ACSMs Health Fit. J. 2018; 22: 10–17. Publisher Full Text\n\nThompson WR: Worldwide Survey of Fitness Trends for 2020. ACSMs Health Fit. J. 2019; 23: 10–18. Publisher Full Text\n\nThompson WR: Worldwide Survey of Fitness Trends for 2022. ACSMs Health Fit. J. 2022; 26: 11–20. Publisher Full Text\n\nThompson WR: Worldwide Survey of Fitness Trends for 2023. ACSMs Health Fit. J. 2023; 27: 9–18. Publisher Full Text\n\nBrophy K, Davies S, Olenik S, et al.: The Future of Wearable Technologies. 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}
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[
{
"id": "342644",
"date": "30 Dec 2024",
"name": "Stuart Evans",
"expertise": [
"Reviewer Expertise Wearable sensors",
"youth development",
"long-term athletic development."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors, I commend you all for taking on what is a huge subject that requires much focus and dedication. However, I cannot recommend your indexing in its current form as much of your literature and topics simply do not provide a clear link to youth. Firstly, you need to define what you mean by youth. A youth athlete will vary significantly depending on their age - biomechanics, physiology, motor control, sleep, reaction time ... all will vary simply due to the level of maturation of the youth athlete. You need to consider these factors when reviewing why a wearable will be used, how it will be used, when it will be used, why it will be used (i.e., as a motivational tool?), and where (in school, out of school, recreational activity, sport).\n\nI have provided examples below.\n\nAbstract Comment 1: Define Youth.\nAssessment of activity and health Comment 2: The subheading talks to movement and physical activity tracking, yet the opening paragraph mentions sport. There is a huge difference between sport, physical activity and movement tracking. I suggest you define these terms.\n\nThe information listed here is very informative, yet I cannot see a tangible link to youth. What evidence exists that youth are using wearables to monitor step count? A school-based intervention may increase youth participation in wearable usage, but it is unclear how your summary relates to youth either in an education setting or external (recreational).\nHeart rate and heart rate variability monitoring Comment 3: The same issue exists here I’m afraid as this reads more like a literature review of wearables and not a review of how, why, when, and how youth use them. For instance, you talk about an athlete’s heart. The youth heart and contractile elements are still growing depending on the child’s age. How would wearable technology be used here? And why would a youth athlete use it and not the coach? There is no linkage between the information presented and the contemporary youth athlete.\n\nEnergy expenditure, Sweat sensing and Sleep monitoring Comment 4: And again. Great information, but why is this relevant for a youth athlete? It is highly debatable if a youth athlete would monitor sweat rates as this implies that the youth understands basic physiological changes and responses to activity. Moreover, given that youth athletes have immature physiological systems and varied responses to exercise intensity, how would the wearable data be used? There must be a stronger and more robust link to the information provided and the topic of youth athletes.\n\nPerformance feedback for training Comment 5: You state that ‘most existing technology uses wearable inertial measurement unit (IMU) or force sensors to measure the joint angles, accelerations, and interaction forces of young athletes.’ This needs a citation. Also, an IMU won’t measure the joint angle but will provide angular acceleration or a velocity component. You also state that ‘these devices then use data analysis methods and classification-based machine learning (ML) algorithms to assess performance during the training session.’ Is this correct? Many IMU do not rely on machine learning but simply require the transfer of raw data. Also, you are implying that this is real-time data analysis. How is the data being fed back to the youth athlete? The rest of this section is confusing. You mention a Kalman filter but there is no context applied whatsoever. Also, laboratory wearable systems are mentioned. The general purpose of wearable systems is to avoid the lab environment. My biggest concern is that much of the literature stated here does not relate to youth. Many of the studies that you have cited are not based on youth activity or youth wearables.\n\nResistance training Comment 6: How can “wearable devices can also improve the performance of young athletes during resistance training.”? Adolescent resistance training requires knowledge of sets, reps, recovery periods, relative strength of the youth, appropriate loading and correct technique. You’ve included studies that have not focused on youth.\nBiofeedback Comment 7: What wearables are being referred to? Biofeedback is hugely complex and there is no consideration for the age of the youth or level of maturation. Is the wearable being used as a educational tool for the youth athlete? How is the data being used?\nMuscle stimulation Comment 8: There are huge ethical considerations with muscle stimulation techniques in children under the age of 18, yet these are not mentioned.\nAthletic motivation Comment 9: This is arguably the most important section as wearables and relative data can be used as motivational tool and/or as a learner centric tool for youth, yet this isn’t expanded on. I would expect to see references for efficacy, goal-setting, self-determination theory, etc.\n\nRehabilitation of athletes Comment 10:. Is “the US is experiencing a shortage of rehabilitation therapists”? If so, where is the citation? There is no mention of tele-health or how wearables could be used by a therapist to monitor training loads or peaks with the athlete reporting back on progress. Training and performance enhancement\nComment 11: Everything that you have stated is correct, but again the question is how? How does this relate to young athletes? How can young athletes uses wearables to monitor performance? How can this fit with long term athletic development models to progress performance?\nGlobal positioning system Comment 12: And here. Why would a young athlete use GPS? This has to link to a goal, a motivation or similar.\n\nI reviewed the section on IMU sensors to Future directions of wearable technology in sports. The latter section at least makes a clear link to the youth athlete. The other sections simply do not provide a link or a rationale to the relevance of youth.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? No",
"responses": []
},
{
"id": "348486",
"date": "11 Jan 2025",
"name": "Fergus Guppy",
"expertise": [
"Reviewer Expertise Wearable technology",
"remote monitoring",
"athlete performance"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors are to be commended for conducting a thorough review of the literature around wearable technology, however it feels that the focus of the review could be rethought, with the link back to the practitioner and why they should consider measuring these things using wearable technology allowing them to compare to the laboratory measures of the same outcomes.\n\nThere is also limited linking back to youth athletes, with the focus very much on the technology. This is therefore, not reflected in the title of the work.\n\nThere is also detail here on devices work (e.g. accelerometers and MEMSs). Is that vital information for the understanding of the data collected? This links back to the question about what is the aim of this piece. Currently does not feel that it is achieving the aim.\nSee below some specific comments on various sections What wearable technology can do:\nL1 – wearable tech does not need to be worn on the skin, could be worn close to it so would suggest amending this.\nL9 list with lots of ands in. This could do with revision.\nRef 24 - This is an undergraduate thesis. Is this the most appropriate source for this information? Also would suggest that this part needs clarification due to the use of distance covered. Does this mean the distance covered by the ball or by the golfer walking the course? I would suggest clarifying this and providing a more appropriate (preferably peer reviewed) source for this information.\nHR/HRV – Not sure of the relevance of the athlete heart here. How does this relate to sensor wearing? This can’t be determined using wearable technology, again seems to be outside of the focus on wearable technology in youth athletes.\nHow much variation is there between wrist based vs chest worn HR straps? How would this change the determination of which is more important the athlete comfort v data quality. What recommendations would you make?\nEnergy Expenditure Same point re HR. How do the wearable estimates of EE compare to lab based measures? This is key information for people trying to understand the data that they might collect using these devices.\nTraining monitoring and assessment Kalman filter- what is the relevance of this? How does it impact the data that is collected/reported by the device?\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1381
|
https://f1000research.com/articles/13-1380/v1
|
18 Nov 24
|
{
"type": "Systematic Review",
"title": "The effectiveness of physical therapy for temporomandibular disorder: A systematic review",
"authors": [
"Arum Nur Kartika Putri",
"Dewati Ayusri Artha",
"Ganendra Anugraha",
"Liska Barus",
"Muhammad Ruslin",
"Ardiansyah Syahrom",
"Ni Putu Mira Sumarta",
"Arum Nur Kartika Putri",
"Dewati Ayusri Artha",
"Ganendra Anugraha",
"Liska Barus",
"Muhammad Ruslin",
"Ardiansyah Syahrom"
],
"abstract": "Background Temporomandibular disorders (TMD) are diseases of the stomatognathic system characterized by various signs and symptoms. TMD treatment must be multidisciplinary because its causes are multifactorial. Noninvasive conservative treatment strategies should be carried out before considering invasive treatment options that may lead to irreparable damage. Physical therapy is an effective noninvasive therapy for managing the signs and symptoms of TMD. To date, the most effective therapeutic approach for managing TMD pain remains controversial. Therefore, this study aimed to evaluate the most effective physical therapy for pain management, symptom control, and quality of life improvement in patients with TMD.\n\nMethods Data search was performed using the PubMed, SCOPUS, and Web of Sciences databases. The results are reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews. Interventions based on physical therapy, including physical exercise, manual therapy, myofacial muscle manipulation, and postural therapy, with pain relief, increased mouth opening, or improved quality of life as primary outcomes, were examined.\n\nResults Twenty eligible articles were analyzed. Most interventions demonstrated statistically significant improvements as measured by the study outcomes.\n\nConclusions Most types of physical therapy demonstrated positive effects on patients with TMD. Furthermore, physical therapy for both cervical and regional TMJ manipulation can be an alternative long-term treatment for TMD.",
"keywords": [
"Temporomandibular disorders",
"TMD",
"physical therapy",
"manual therapy",
"quality of life"
],
"content": "Introduction\n\nTemporomandibular disorders (TMD) are diseases of the stomatognathic system that affect the musculoskeletal system’s bone structure and muscle tissue (Li et al., 2017). The temporomandibular disorder affects about 10% of the adult population and is three times more common in women (Jasim et al., 2020). In contrast, another source states that the overall prevalence of TMD occurs in 31% of adults and 11% in children and adolescents (Santos et al., 2022).\n\nRisk factors of TMD include congenital abnormalities, inflammatory conditions, systemic diseases, depression, stress, and other psychological factors (Jasim et al., 2020; Heir, 2016; Murphy et al., 2013). Signs and symptoms of TMD include masticatory muscle pain, temporomandibular joint pain, joint sounds, reduced mandibular range of motion, and jaw deviations when opening and/or closing the mouth (Wilkowicz et al., 2020). Consequently, TMD can interfere with daily social activities. In particular, prolonged pain, affective and cognitive balance disorders, sleep disorders, and limitations on physical activities, can adversely influence systemic health and the patient’s quality of life (de Resende et al., 2013).\n\nTMD treatment must be multidisciplinary because its causes are multifactorial. The literature reports various treatment options proposed by dentists, oral surgeons, orthodontists, psychologists, physical therapists, and physicians. Primarily, treatment is divided into non-invasive conservative therapy and invasive surgery (Cúccia et al., 2010). Treatment results vary from study to study (Wright et al., 2000; Ismail et al., 2007; Reynolds et al., 2020). Non-invasive treatment should be considered before resorting to invasive treatment that could cause irreparable damage. Noninvasive therapies include pharmacological agents, acupuncture, educational programs, home exercises, physical therapy, osteopathy, and relaxation (Cúccia et al., 2010).\n\nTMD treatment aims to reduce pain, control symptoms, reduce injury severity, and improve quality of life by improving masticatory function, joint mobility, and patient knowledge (de Resende et al., 2021). Physical therapy is intended to relieve musculoskeletal pain, reduce inflammation, and restore oral motor function (Cúccia et al., 2010). Physical therapy is believed to be an effective treatment option for managing the signs and symptoms of TMD. Therapies include voltage electrical stimulation, acupuncture, laser therapy, muscle relaxing appliances, massaging the masticatory muscles, therapeutic exercises for the masticatory or cervical muscles, and manual therapy techniques (de Paula Gomes et al., 2014).\n\nCurrently, a consensus on the most effective therapeutic approach for TMD pain is lacking. Physical therapy of the TMJ is noninvasive and offers positive advantages. Therefore, this study aimed to evaluate the most effective physical therapy for pain management, symptom control, and quality of life improvement in patients with TMD.\n\n\nMethods\n\nThis study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. This study was registered in the PROSPERO database (CRD42023490893). The modified PICOS questions were used as the basis for searching for the selected criteria.\n\n1. Population (P): Adult patients diagnosed with TMD.\n\n2. Intervention (I): Physical therapy, including physical exercise, manual therapy, postural therapy (postural and cervical manipulation), and myofacial muscle manipulation.\n\n3. Comparison (C): Not applicable to items included in this review.\n\n4. Primary outcomes (O): Pain, TMJ range of motion, TMJ sound, masticatory muscle activity, mandibular function, quality of life, and sleep quality.\n\n5. Study design (S): Randomized controlled trial and case series.\n\nThe PubMed, SCOPUS, and Web of Sciences databases were searched. The database used search terms from the Medical Subject Headings (MeSH) vocabulary and was last searched on July 31, 2023. The keywords used for search on PubMed were [(“TMD” or “temporomandibular joint disorders” or “temporomandibular disorder”) AND (“physical therapy” or “physical exercise” or “postural therapy” or “manual therapy”)]. The keywords used in the Web of Science were ((TMD OR temporomandibular joint disorder OR temporomandibular disorder)) AND AB=(physical therapy OR physical exercise OR postural therapy OR manual therapy). The keywords used for search on Scopus were TITLE-ABS KEY (“TMD” OR “temporomandibular joint disorder” OR “temporomandibular disorder”) AND (“physical therapy” OR “physical exercise” OR “postural therapy” OR “manual therapy”) AND (“clinical trial” OR “randomized controlled trial”) AND ( LIMIT-TO (SRCTYPE, “j”)) AND ( LIMIT-TO (OA, “all”)) AND (LIMIT-TO (PUBSTAGE, “final”)) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (LANGUAGE, “English”)).\n\nTwo authors (ANKP and DAA) removed duplicate studies using EndNoteTM20 (version 20.4.0.18004) software. Only studies in English were included and review article restrictions were placed on the publication date. Study selection was conducted in two stages. Article titles and abstracts were reviewed in the first stage to assess eligibility based on predetermined inclusion and exclusion criteria. Subsequently, the remaining articles were searched and evaluated. Subsequently, the remaining articles were searched and evaluated.\n\nThe inclusion and exclusion criteria were determined before study identification. The inclusion criteria were as follows: randomized controlled trial (RCT) and case series design, adult population (>18 years old) with TMD diagnosis, intervention with physical therapy including physical exercise, manual therapy, postural therapy, or myofacial muscle manipulation, no comorbidities, not undergoing orthodontic treatment, never undergoing surgery, with outcome study pain relief, increased range of motion, reduced TMD signs and symptoms, improved activity of the masticatory muscles and mandibular function, and improved quality of life and sleep. The exclusion criteria were as follows: history of trauma in the TMJ area, inflammatory and rheumatic diseases (e.g., rheumatoid arthritis), congenital abnormalities, and non-human studies.\n\nThree authors (NPMS, MR and AS) reviewed the full text of relevant articles to determine the eligibility criteria. If there was disagreement among the authors, the final decision was made through discussion by majority vote. The following data were extracted: year of publication, sample size, TMD pathology, intervention groups, outcomes, results, and conclusions.\n\nTwo authors (LB and GA) independently assessed the quality of the eligible studies, using 16 items from the Quality Assessment (QATSDD) Tools. Quality assessment was performed by answering all questions. Each question was scored (0-3). The risk of bias was assessed at the outcome level.\n\n\nResults\n\nThe selection of studies and data extraction process for inclusion in this review are summarized in the flow diagram ( Figure 1). Our primary search identified 490 studies with 79 duplicates. Data screening was conducted on 414 studies. After final evaluation, 20 studies, published between 1986 and 2022, were eligible and included in the analysis.\n\nShowing the literature search process, screening, and data extraction.\n\nA summary of the final data characteristics and quality assessment scores is presented in (Table 1) (Extended data). The data included author details, sample sizes, treatment groups, outcomes, and quality assessment scores.\n\nAll patients in this study complained of TMD, including orofacial and myofascial pain, headache, tinnitus, and TMJ dysfunction. Randomized controlled studies with variable sample sizes are included. The patients included in the study ranged in age from 18 to 65 years. The total sample size was 1016 patients from the 20 articles analyzed.\n\nThe interventions investigated in the eligible studies included physical therapy, such as manual therapy, postural therapy, myofascial therapy, and home exercises, either in combination or separately. Physical exercise protocols varied widely. Protocols described included cervical-related postural correction, intraoral myofascial exercises, facial muscle relaxation, and home-based physical exercises. Some interventions were compared or combined with splint therapy, education, and hot and cold compression. Physical therapy interventions were mostly scheduled and assisted by physiotherapists. However, some studies did not specify the professional who assisted with the physical therapy.\n\nManual therapy (stomatognathic treatment) versus acupuncture\n\nOnly one study has compared manual therapy with acupuncture. Patients in the manual therapy group who underwent stomatognathic treatment were administered occlusal adjustment therapy and muscle coordination exercises for the lower jaw. Positive results were observed in both groups. The study reported pain reduction during mouth opening, lateral mandibular movements, and jaw protrusion in both groups. The study concluded that the treatment effect was similar in both groups, but those in the acupuncture group reported an irritating effect during therapy administration (Raustia and Pohjola, 1986).\n\nPostural and cervical manipulation versus no therapy, conservative therapy (oral appliance), or suboccipital treatment\n\nFive studies discussed manual therapy that focused on postural, cervical, and upper thorax manipulation therapy (Cúccia et al., 2010; Wright et al., 2000; Reynolds et al., 2020; George et al., 2007; Packer et al., 2015). Wright et al. (2000) investigated the effects of postural exercises under the supervision of a physiotherapist, that aimed to stretch and strengthen anatomical structures that were compromised due to poor posture. The results showed an increased mean maximum pain-free opening and improved TMD symptoms in the postural therapy group. Reynolds et al. (2020) used the cervical spine high-velocity low-amplitude thrust (HVLAT) technique, which consisted of exercises in a resting position, controlled opening, axial extension of the neck with overpressure, posture correction, and scapular retraction. This study showed that individuals with TMD who received HVLAT treatment of the cervical spine experienced significant improvements in jaw function and reduced fear of movement relative to the sham group. George et al. (2007) also used the HVLAT technique and compared it to the active release technique (ART), which focuses on the suboccipital musculus. The study reported that the degree of mouth opening between the two groups was similar.\n\nIn contrast, Cúccia et al. (2010) provided treatment directed toward the cervical region using gentle techniques, such as myofascial release, balanced membrane tension, muscle energization, joint articulation, HVLAT, and cranial-sacral therapy. There were no significant differences in the VAS, MOV, and ROM scores between the manual therapy group and the conventional therapy group treated with oral appliances. In addition, Packer et al. (2015) manipulated the upper thorax at the T1 vertebral segment in their experimental group. The patient was instructed to link the fingers behind the neck. The therapist placed the stabilizing hand under the segment to be manipulated (T2) and directed the arm caudally to encourage thoracic spine flexion. The results showed that vertical mouth opening did not differ between the manual therapy versus the sham manipulation groups. However, in the upper thoracic manipulation group, an increase in EMG activities in the left masseter and suprahyoid muscles was observed.\n\nTMJ and orofacial muscle manipulation versus splint therapy, education, TENS, or no therapy\n\nSix studies examined the effects of manual therapy, focusing on manipulation of the TMJ region and the orofacial muscles. Three studies compared manual therapy with splint therapy (Ismail et al., 2007; de Paula Gomes et al., 2014; Damar et al., 2022). Three other studies compared manual therapy with various therapies, namely, splint therapy and education (de Resende et al., 2021), TENS therapy (Patil and Aileni 2017), and no therapy (Vivanco-Coke et al., 2020).\n\nIsmail et al. (2007) reported significantly higher active jaw opening after physical therapy by mobilizing the TMJ joint accompanied by jaw-lifting and muscle-blasting exercises. De Paula Gomes et al. (2014), who provided therapy with massage of the masticatory muscles, also reported maximum mouth opening, similar to that of therapy using splints. Damar et al. (2022), who provided therapy for soft tissue and joint mobilization of the TMJ and surrounding structures, reported significant results in reducing pain, increasing the range of motion and TMJ function, and improving sleep quality, relative to splint therapy.\n\nde Resende et al. (2021) investigated manual therapy, splint therapy, education and splint therapy, and education in improving quality of life and sleep quality and reported effective short-term alleviation of TMD symptoms. Research comparing manual therapy with TENS has also shown effective results in improving mouth opening and reducing masticatory muscle and joint pain after treatment in both groups. Patients who underwent manual therapy performed an exercise program consisting of active and passive jaw opening and closing exercises, isometric jaw exercises, jaw stretching exercises, and resistive jaw exercises. Furthermore, Vivanco-Coke et al. (2020) demonstrated a clinically significant reduction in pain and dysfunction in patients who underwent manual therapy and superficial myofascial release, strain-counterstrain technique, and deep transverse massage.\n\nPatient undertook manual therapy perfomed active and passive jaw exercises consisting jaw opening, closing, isometric, stretching, and restrictive movement (Patil and Aileni 2017). Furthermore, Vivanco-Coke et al. (2020) stated that patients who undertook manual therapy and superficial myofascial release, strain-counterstrain technique, and deep transverse massage showed a significant clinical improvement in reduction of pain and dysfunction.\n\nPostural and cervical manipulation versus postural and cervical manipulation with TMJ and orofacial muscle manipulation\n\nThree studies discussed additional TMJ and orofacial muscle manipulation. von Piekartz and Lüdtke (2011) compared two groups in their study. The first group received manual therapy for the cervical region, and the second group received additional manual therapy for the temporomandibular region. Additional manual therapy techniques included translational movements of the temporomandibular region and masticatory muscle techniques, such as trigger point treatment and muscle stretching. In the additional manual therapy group, treatment effects lasted for six months. Garrigós Pedrón et al. (2018) in their study compared the cervical group with the cervical and orofacial groups. Therapy for the cervical group consisted of suboccipital muscle inhibition, passive cervical joint mobilization in the supine and prone positions, co-contraction of flexors and extensors, and exercises of increasing difficulty and resistance using a latex band and nerve tissue techniques. In the cervical and orofacial groups, therapy was augmented with bilateral caudal longitudinal techniques for the TMJ, neuromuscular techniques for the masseter and frontal muscles, and coordination exercises for the masticatory muscles. The study concluded that a combination of cervical and orofacial treatments was more effective.\n\nDelgado De La Serna et al. (2020) compared self-care manual therapy with additional cervical therapy provided by physiotherapists. This group underwent inferior glide accessory mobilization of the mandible and soft tissue mobilization of the masseter and temporalis muscles. After three and six months, the group that received additional manual therapy from a physiotherapist demonstrated significantly better clinical, psychological, and physical outcomes than self-care manual therapy.\n\nIntraoral myofascial manipulation versus intraoral myofascial manipulation with self-care exercises and education, or self-care exercises and education\n\nTwo separate studies by the same research group discussed intraoral myofascial manipulation. The primary author also performed intraoral myofascial manipulations. In the first study, Kalamir et al. (2010) compared intraoral myofascial manipulation with intraoral myofascial manipulation plus self-care exercises and education. Three intraoral myofascial intervention techniques including intraoral temporalis release, intraoral medial and lateral pterygoid techniques, and intraoral sphenopalatine ganglion technique, were described. All treatment groups demonstrated overall improvement.\n\nThe second study compared intraoral myofascial manipulation therapy with self-care and education. The therapy protocol was the same as that used in a previous study. The results concluded that intraoral myofascial manipulation was superior in reducing pain compared with self-care and education as short-term treatment (Kalamir et al., 2013).\n\nIntraoral myofascial manipulation versus extraoral myofascial manipulation\n\nOnly one study compared intraoral and extraoral manipulations. Intraoral myofascial manipulation uses post-metric muscle relaxation treatments (PIR), whereas intraoral myofascial manipulation uses myofascial release treatment (MR). The results of this study suggest that both PIR and MR can be used to treat TMD-associated pain and masticatory muscle tension (Urbański et al., 2021).\n\nTMJ active exercises versus TMJ active exercises with Jog-type jaw manipulation, or masticatory muscle exercise\n\nTwo studies compared active TMJ exercises with other exercises. Bae and Park (2013) compared active TMJ and muscle exercises. These two studies also included self-care exercises. In the masticatory muscle exercise group, the patients were instructed to bring their lips together, place the front third of the tongue on the palate with the upper and lower teeth not touching each other, and then, apply a light force to push the tip of the tongue forward. The TMJ active exercise group received mouth opening and closing therapy. The results showed that TMJ pain, jaw deviations, and the mandibular range of motions improved in both groups. Nagata et al. (2019) provided active TMJ exercises to encourage condyle displacement by using simplified myofunctional therapy that pulled on the back molars. The comparison group was treated with jog-type jaw manipulation developed by the authors. The results of this study showed no statistical differences in mouth opening limitations, pain, or TMJ sounds between the two groups.\n\n\nDiscussion\n\nThis systematic review aimed to determine the effectiveness of physical therapy in patients with TMJ disorders. The types of physical therapy we evaluated included noninvasive physical therapy without the use of tools, such as manual therapy, postural training, muscle massage, and physical self-care exercises. In the selected articles, an efficiency analysis on the effects of pain intensity, TMJ range of motion, TMD signs and symptoms, activity of the masticatory muscles, mandibular function, quality of life and sleep quality was performed.\n\nAll studies were randomized controlled trials involving human subjects. The results showed heterogeneity among the studies in terms of the research sample, interventions provided, and outcome measurement tools. The best TMD treatment remains controversial. Hence, recommending a specific noninvasive physical therapy interventions is not possible. Numerous types of physical therapy for TMD may be due to the multifactorial etiology of TMD. Therefore, we attempted to compare the various interventions. However, there were two comparisons in which only one study met the inclusion criteria.\n\nPostural and cervical manipulations using the HVLAT technique were performed in two studies. Reynolds et al. (2020) demonstrated improved results using the HVLAT technique. Jaw function and the fear of jaw movement improved after treatment. However, a previous review did not show significant differences between the HVLAT and ART techniques (George et al., 2007). Manual therapy of the cervical spine using the HVLAT technique did not significantly improve mouth opening when compared with the ART technique. Evidence supports the use of cervical spinal joint mobilization for the treatment of TMD. The cervical spine HVLAT technique is a noninvasive physical therapy consisting of several cervical region manipulations. The advantage of this method is that side effects are superficial.\n\nPostural and cervical manipulations are often combined with TMJ and orofacial muscle manipulations as physical therapies for TMD. The combination of manipulation in both areas improved the outcome, especially when therapy was provided over an extended treatment period (von Piekartz and Lüdtke, 2011; Garrigós Pedrón et al., 2018; Delgado De La Serna et al., 2020). Bevilaqua-Grossi et al. (2016), also reported that manual therapy and exercises to the cervical spine improved the symptoms of patients with migraine, cervical pain, and TMD.\n\nCervical pain is often observed in patients with TMDs. A close relationship exists between pericranial, masticatory, and cervical muscle tenderness and the presence of TMD and neck disability. in the study of Almoznino et al. (2020) conducted a study on the severity of cervical pain and myalgia disability and found a significantly positive relationship between the severity of cervical pain and headaches and other body pain, with limited mobility of the mandible, such as pain when opening.\n\nManipulation of the TMJ and orofacial muscles as physical therapy can also be together for TMD treatment. Analysis of the main results showed that the pain scores before treatment were significantly lower in the TMJ and orofacial muscle groups than in the control group, but the difference was not clinically significant after short-term treatment. Given these results, many researchers have suggested that longitudinal studies of myofascial treatment and self-care exercises for TMD should be conducted to assess their potential effectiveness (Kalamir et al., 2013).\n\nThe myofascial therapy conducted by Urbański et al. (2021) compared intraoral and extraoral myofascial manipulations. Both methods reduced the increased tension in the anterior part of the temporal and masseter muscles and the electrical activity of the masticatory muscles in the mandibular resting position in patients with TMD. The authors suggested that this therapy should be considered as supportive therapy for patients with TMD.\n\nSeveral eligible studies compared splint therapy with physical therapy of the TMJ and orofacial muscles. All physical therapies on the TMJ and orofacial muscles yielded positive results, including higher active jaw opening, maximum mouth opening, reduced pain, and improved sleep quality (Ismail et al., 2007; de Paula Gomes et al., 2014; Damar et al., 2022). Splint therapy, widely used as a single therapy, has no additional effect compared with noninvasive physical therapy interventions. Noninvasive physical therapy interventions can be considered in addition to splint therapy. However, an appropriate selection of noninvasive physical therapy is essential. The diversity of manual techniques and exercises may lead to incompatibility between adjunctive physical therapy and splint therapy, and thus, affect treatment effectiveness (La Touche et al., 2020).\n\nOf all the interventions in this review, various methods were beneficial, and some provided the same results as conservative therapies. The variety of TMD complaints with different pathological courses also influences the choice of therapy. When selecting a noninvasive physical therapy method, the operator must consider the patient’s needs and the potential benefits. The choice should be based on interventions that show statistical improvement. Of all the interventions in this review, various methods were beneficial, and some provided the same results as the more commonly used conservative therapies. The variety of TMD complaints with different pathological courses also influences the choice of therapy. To assist with selecting the most appropriate noninvasive physical therapy for TMD, studies that demonstrate significant outcomes are needed.\n\nThe heterogeneity of the sample and intervention characteristics in this study are limitations. The complaints, signs, and symptoms of TMD in each study have unique characteristics. In addition, the timing of the interventions and outcomes varied greatly.\n\nMost non-invasive physical therapies have a positive effect on patients with TMD. Noninvasive physical therapy for both cervical and regional TMJ manipulation may be considered as long-term treatment option for TMD. Several studies have also shown that physical therapy is as effective or superior to splint therapy. However, owing to the diversity of interventions in these studies, the appropriate treatment must be selected carefully based on the patient’s needs.\n\n\nEthical clearance and consent\n\nNot applicable.\n\n\nPatient’s/guardian’s consent\n\nNot applicable.",
"appendix": "Data availability statement\n\nNo data associated with this article.\n\nFigShare ‘The effectiveness of physical therapy for temporomandibular disorder: A systematic review’ https://doi.org/10.6084/m9.figshare.27282534 (Sirriyeh et al., 2012).\n\nThe project contains the following data:\n\n• Table 1 Quality Assesment score\n\nFigShare Database screening and extraction ‘The effectiveness of physical therapy for temporomandibular disorder: A systematic review’ https://doi.org/10.6084/m9.figshare.27328491.v1 (Sumarta, 2024a).\n\nThe project contains the following data:\n\n• Database screening and extraction\n\nFigShare PRISMA checklist ‘The effectiveness of physical therapy for temporomandibular disorder: A systematic review’ https://doi.org/10.6084/m9.figshare.27328572.v1 (Sumarta, 2024b).\n\nThe project contains the following data:\n\n• PRISMA checklist.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAlmoznino G, Zini A, Zakuto A, et al.: Cervical Muscle Tenderness in Temporomandibular Disorders and Its Associations with Diagnosis, Disease-Related Outcomes, and Comorbid Pain Conditions. J. Oral Facial Pain Headache. 2020; 34: 67–76. PubMed Abstract | Publisher Full Text\n\nBae Y, Park Y: The Effect of Relaxation Exercises for the Masticator Muscles on Temporomandibular Joint Dysfunction (TMD). J. Phys. Ther. Sci. 2013; 25(5): 583–586. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBevilaqua-Grossi D, Gonçalves MC, Carvalho GF, et al.: Additional Effects of a Physical Therapy Protocol on Headache Frequency, Pressure Pain Threshold, and Improvement Perception in Patients With Migraine and Associated Neck Pain: A Randomized Controlled Trial. Arch. Phys. Med. Rehabil. 2016; 97(6): 866–874. PubMed Abstract | Publisher Full Text\n\nCúccia AM, Caradonna C, Annunziata V, et al.: Osteopathic manual therapy versus conventional conservative therapy in the treatment of temporomandibular disorders: A randomized controlled trial. J. Bodyw. Mov. Ther. 2010; 14(2): 179–184. PubMed Abstract | Publisher Full Text\n\nDamar Örenler S, Tuncer A, Najafov E: A comparıson of manual therapy and splınt therapy ın patıents dıagnosed wıth myofascıal temporomandıbular dysfunctıon wıth sleep bruxısm. Türk Fizyoterapi ve Rehabilitasyon Dergisi. September 20, 2022; 33: 89–97. Publisher Full Text\n\nDelgado de la Serna P, Plaza-Manzano G, Cleland J, et al.: Effects of Cervico-Mandibular Manual Therapy in Patients with Temporomandibular Pain Disorders and Associated Somatic Tinnitus: A Randomized Clinical Trial. Pain Med. 2020; 21(3): 613–624. PubMed Abstract | Publisher Full Text\n\nde Paula Gomes CAF , El Hage Y, Amaral AP, et al.: Effects of massage therapy and occlusal splint therapy on electromyographic activity and the intensity of signs and symptoms in individuals with temporomandibular disorder and sleep bruxism: a randomized clinical trial. Chiropr. Man. Therap. 2014; 22(1): 43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Resende CMBM , de Oliveira Medeiros FGL , de Figueiredo Rêgo CR , et al.: Short-term effectiveness of conservative therapies in pain, quality of life, and sleep in patients with temporomandibular disorders: A randomized clinical trial. Cranio. 2021; 39(4): 335–343. PubMed Abstract | Publisher Full Text\n\nGarrigós-Pedrón M, La Touche R, Navarro-Desentre P, et al.: Effects of a Physical Therapy Protocol in Patients with Chronic Migraine and Temporomandibular Disorders: A Randomized, Single-Blinded, Clinical Trial. J. Oral Facial Pain Headache. 2018; 32(2): 137–150. PubMed Abstract | Publisher Full Text\n\nGeorge JW, Fennema J, Maddox A, et al.: The effect of cervical spine manual therapy on normal mouth opening in asymptomatic subjects. J. Chiropr. Med. 2007; 6(4): 141–145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeir MG: Assessing Temporomandibular Disorders. Oral and Maxillofacial Surgery. United States: Saunders Elsevier; 2016; II. : 815.\n\nIsmail F, Demling A, Hessling K, et al.: Short-term efficacy of physical therapy compared to splint therapy in treatment of arthrogenous TMD. J. Oral Rehabil. 2007; 34(11): 807–813. PubMed Abstract | Publisher Full Text\n\nJasim H, Ghafouri B, Gerdle B, et al.: Altered levels of salivary and plasma pain related markers in temporomandibular disorders. J. Headache Pain. 2020; 21(1): 105. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalamir A, Graham PL, Vitiello AL, et al.: Intra-oral myofascial therapy versus education and self-care in the treatment of chronic, myogenous temporomandibular disorder: a randomised, clinical trial. Chiropr. Man. Therap. 2013; 21(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalamir A, Pollard H, Vitiello A, et al.: Intra-oral myofascial therapy for chronic myogenous temporomandibular disorders: a randomized, controlled pilot study. J. Man. Manip. Ther. 2010; 18(3): 139–146. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLa Touche R, Boo-Mallo T, Zarzosa-Rodríguez J, et al.: Manual therapy and exercise in temporomandibular joint disc displacement without reduction. A systematic review. Cranio. June 26, 2020; 40: 440–450. Publisher Full Text\n\nLi Q, Huang F, Liu J: Yin Hua Zhao, Zhang M, Yong Jin Chen. Psychological Stress Alters Extracellular Matrix Metabolism in Mandibular Condylar Cartilage. Chin. J. Dent. Res. 2017; 20(3): 125–135.\n\nMurphy MK, MacBarb RF, Wong ME, et al.: Temporomandibular Disorders: A Review of Etiology, Clinical Management, and Tissue Engineering Strategies. Int. J. Oral Maxillofac. Implants. 2013; 28(6): e393–e414. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNagata K, Hori S, Mizuhashi R, et al.: Efficacy of mandibular manipulation technique for temporomandibular disorders patients with mouth opening limitation: a randomized controlled trial for comparison with improved multimodal therapy. J. Prosthodont. Res. 2019; 63(2): 202–209. PubMed Abstract | Publisher Full Text\n\nPacker AC, Pires PF, Dibai-Filho AV, et al.: Effect of Upper Thoracic Manipulation on Mouth Opening and Electromyographic Activity of Masticatory Muscles in Women With Temporomandibular Disorder: A Randomized Clinical Trial. J. Manip. Physiol. Ther. 2015; 38(4): 253–261. PubMed Abstract | Publisher Full Text\n\nPatil SR, Aileni KR: Effect of Transcutaneous Electrical Nerve Stimulation versus Home Exercise Programme in Management of Temporomandibular Joint Disorder. J. Clin. Diagn. Res. 2017. Publisher Full Text\n\nRaustia AM, Pohjola RT: Acupuncture compared with stomatognathic treatment for TMJ dysfunction. Part III: Effect of treatment on mobility. J. Prosthet. Dent. 1986; 56(5): 616–623. PubMed Abstract | Publisher Full Text\n\nde Resende CMBM , de Alves AC , Coelho LT, et al.: Quality of life and general health in patients with temporomandibular disorders. Braz. Oral Res. 2013; 27(2): 116–121. PubMed Abstract | Publisher Full Text\n\nReynolds B, Puentedura EJ, Kolber MJ, et al.: Effectiveness of Cervical Spine High-Velocity, Low-Amplitude Thrust Added to Behavioral Education, Soft Tissue Mobilization, and Exercise for People With Temporomandibular Disorder With Myalgia: A Randomized Clinical Trial. J. Orthop. Sports Phys. Ther. 2020; 50(8): 455–465. PubMed Abstract | Publisher Full Text\n\ndos Santos EA , Peinado BRR, Frazão DR, et al.: Association between temporomandibular disorders and anxiety: A systematic review. Front. Psych. 2022; 13: 13. Publisher Full Text\n\nSirriyeh R, Lawton R, Gardner P, et al.: Reviewing studies with diverse designs: the development and evaluation of a new tool. J. Eval. Clin. Pract. 2012 Aug; 18(4): 746–752. Publisher Full Text\n\nSumarta NPM: Database screening and extraction. figshare. [Dataset]. 2024a. Publisher Full Text\n\nSumarta NPM: PRISMA checklist. figshare. [Dataset]. 2024b. Publisher Full Text\n\nUrbański P, Trybulec B, Pihut M: The Application of Manual Techniques in Masticatory Muscles Relaxation as Adjunctive Therapy in the Treatment of Temporomandibular Joint Disorders. Int. J. Environ. Res. Public Health. 2021; 18(24): 12970. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVivanco-Coke S, Jiménez-Silva A, Rios-Quiñinao F, et al.: Evaluation of Short-Term Effectiveness of Orthopedic Manual Therapy in Signs and Symptoms of Myofascial Pain: A Controlled Clinical Trial. J. Oral Res. 2020; 9(2): 116–120. Publisher Full Text\n\nvon Piekartz H , Lüdtke K: Effect of Treatment of Temporomandibular Disorders (TMD) in Patients with Cervicogenic Headache: A Single-Blind, Randomized Controlled Study. Cranio. 2011; 29(1): 43–56. PubMed Abstract | Publisher Full Text\n\nWilkowicz W, Byś A, Zieliński G, et al.: The impact of stress on psychological and physiological aspects of health of patients with TMD: A literature review from 2015–2020. Pol. Ann. Med. January 1, 2020. Publisher Full Text\n\nWright EF, Domenech MA, Fischer JR: Usefulness of posture training for patients with temporomandibular disorders. J. Am. Dent. Assoc. 2000; 131(2): 202–210. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "364032",
"date": "08 Feb 2025",
"name": "Maurits K. A van Selms",
"expertise": [
"Reviewer Expertise TMDs",
"bruxism",
"psychological distress"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors,\nI reviewed the manuscript entitled \"The effectiveness of physical therapy for temporomandibular disorder: A systematic review\". The authors aimed to evaluate, by means of performing a systematic literature review, the most effective physical therapy for pain management, symptom control, and quality of life improvement in patients with TMD. Unfortunately, I regret to say that the manuscript is not suitable for indexing in F1000Research in its present form.\nSince many systematic reviews have already been performed on the effectiveness of physical therapy on TMD complaints, the current study appears something like a rehash of earlier review studies, but less well executed. For me, the most important sentence of the manuscript is ‘The heterogeneity of the sample and intervention characteristics in this study are limitations. The complaints, signs, and symptoms of TMD in each study have unique characteristics’. In other words, it was not possible to draw any conclusion because of the diversity in studies and outcomes. For a large part, this heterogeneity is due to the authors’ approach of conducting this study.\nLet me explain:\nIt is widely acknowledged that TMDs are a heterogeneous group of conditions affecting the temporomandibular joints, the jaw muscles, and the related structures [Manfredini D. et al 2025 (Ref-1)]. The classically described triad of clinical signs and symptoms for TMDs is muscle and/or TMJ pain, TMJ sounds, and altered jaw movements. Not differentiating between painful & non-painful conditions leads to a biased interpretation of the \"TMDs\" concept. Since all kinds of TMDs conditions were included in the literature search (even tinnitus: why??), it’s not surprising that a large heterogeneity of the sample characteristics was found. Dozens of (combinations) of physical therapy modalities were retrieved after the search. In other words, this automatically leads to a large heterogeneity in study characteristics. Again, this concerns me, because a closed lock asks for a different therapeutical approach than sore jaw muscles.\n\nUnfortunately, I can’t open Table 1 Quality Assesment score. At the same time, I know that such studies vary in quality/ risk of bias. When I check the systematic reviews on, for example acupuncture (e.g., da Silva Mira et al., Di Francesco et al., Oliveira Peixoto et al.), it’s obvious that there is a generally a low certainty of evidence/ the evidence for acupuncture as a symptomatic treatment of TMD is limited/ similar results were also observed in the groups treated with placebo acupuncture/ a high risk of bias. In other words, there is also heterogeneity in the quality of the included studies.\nIn summary: to my opinion, it is not possible to reach a clear answer to the study question (most effective physical therapy) with the current methodology.\nAccording to most (international) definitions, TMD is not considered a ‘disease’.\n[1] Manfredini D, Haggman-Henrikson B, Al Jaghsi A, et al. Temporomandibular disorders: INfORM/IADR key points for good clinical practice based on standard of care. Cranio 2025(Ref-1):1-5\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? No\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1380
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https://f1000research.com/articles/13-1378/v1
|
18 Nov 24
|
{
"type": "Research Article",
"title": "Decoding Investor Sentiments in the Indian Stock Market: A Structural Equation Modelling Approach",
"authors": [
"Dr.Farman Ali",
"Anu Sayal",
"Pradeep Suri",
"Mr. Sanjay Singh Chauhan",
"Vasim Ahmad",
"Dr.Farman Ali",
"Pradeep Suri",
"Mr. Sanjay Singh Chauhan",
"Vasim Ahmad"
],
"abstract": "Background of the study This research examines how psychological and social biases affect individual investors’ investing decisions. Investor sentiment significantly influences financial markets, frequently causing stock prices to deviate from their intrinsic values. In rising economies such as India, where retail investors are significantly affected by psychological factors, comprehending these attitudes is crucial.\n\nMethods This study analyses data from a comprehensive questionnaire that was conducted throughout the nation and included 552 retail investors. The investigation employed structural equation modelling (SEM) to identify the elements that influence the decision-making of individuals who invest in the Indian stock market.\n\nFindings The research offers insight on the influence that investor attitude has on investment decision-making as well as the factors that precede it. The study demonstrates that investors make financial decisions based on sentiment. In addition to assessing the efficacy of the Indian financial market, this study sought to ascertain the rationality of investors’ choices by exploring the factors that influence their decision-making process.\n\nConclusion The outcome of the study shows that information seeking, anchoring, herding, representativeness, and overconfidence all have a big impact on investors. Moreover, the study has proven investors’ irrationality and stock market inefficiency. The findings may be employed to further examine the trading practices of international investors and encourage further study in the field of behavioural finance.",
"keywords": [
"Investment decision",
"Investors sentiments",
"stock market",
"behavioural finance",
"irrationality of Investor"
],
"content": "Introduction\n\nOver the last decade, academics have focused on the relationship between investor emotions and market performance. Investor sentiment refers to the anticipated future earnings (returns) and the associated risk that market participants have regarding their investments (De Long et al., 1990). Traditional hypotheses in the stock market primarily emphasized the efficient market hypothesis (EMH) and random walk theory, neglecting the importance of investor mood (Vishwanath & Krishnamurti, 2009). Nevertheless, they were unable to elucidate the diverse behaviours exhibited by investors in the capital market. Investor sentiment significantly influences the capital market, leading to fluctuations in stock prices and creating uncertainty over future returns. Over the past several decades, the financial environment in India has seen substantial transformations, transitioning from an economy focused on savings to one that emphasizes investment. The ninth goal of the Sustainable Development Agenda strives to construct resilient infrastructure, encourage inclusive and sustainable industrialization, and encourage innovation. To achieve this, we must support innovative, sustainable technology and enable widespread, equal access to information and financial markets. Research has shown that individual investors often make irrational decisions, with factors such as heuristics, mental accounting, greed, fear, mental dissonance, and anchoring affecting decision-making (Schmeling,2009; Kumari & Mahakud, 2016; Narasimha & Mushinada, 2020). Herding behavior in the Chinese and Indian stock markets is more prevalent amidst market upswings, while in India, it occurs during market fluctuations (Wen et al., 2019). Factors such as risk tolerance, the soundness of the Indian economy, media concentration on the stock market, political stability, and government policy towards business significantly affect retail investors’ attitudes regarding equity stock investment. Financial literacy is also a key factor in individual saving, with older individuals being more likely to have positive savings. Classical financial theory presupposes a well-functioning market, rational investors, and asset prices that accurately reflect the most important market information (Ouzan, 2020). Because the present value of future cash flows defines asset values in an efficient market, asset prices are not believed to be impacted by investor mood. Nevertheless, there are many examples in financial market history when classical theory fails to adequately explain the actions of asset values, particularly during times of speculation and crises. Finding out how individual, foreign, and institutional investors affect the performance of the stock market is the main goal of this article. We delve further into the topic of how investors act and its impact on the Indian stock market.\n\nResearcher (Al-Tamimi, 2006) found that an investor’s investing attitude, associated norms, and apparent behavioural control influence their investing intent. Gender plays a significant role in the relationships between investment attitude and psychological components, behavioural intentions and attitude, behavioural intention and subjective standards, and behavioural intention and perceived behavioural control. Dash (2010) examined the key characteristics driving investment behaviour and how these aspects affect investors’ risk tolerance and technique process among people of various ages. De et al. (2011) found that behavioural biases had a greater economic impact on individual investors than other investors, and overconfidence caused more wealth loss than disposition effects. Chaudhary (2013) explored the meaning and significance of behavioural finance and its applicability in investment decisions, revealing that anchoring, overconfidence, herd behaviour, over and under-reactions, and loss aversion are all factors that influence investors’ investing decisions. Kartašova (2013) investigated the characteristics that shape irrational individual investor behavior in the Lithuanian stock market, using literature review, theoretical insight comparison, networking, benchmarking analogy, and generalization. He found that overoptimism, anchoring, mental accounting, and herd actions had a higher impact on their financial decision-making process. Kumari and Mahakud (2015) experimentally examined investor sentiment and stock return volatility in the Indian stock market, finding that volatility persists and has clustering, asymmetry, and leverage effects due to investors’ psychological biases and herding tendencies. Thulasipriya (2015) investigated investors’ preferences for various investment channels and their investing pattern, finding that Indian investors, even high-income, well-educated, paid, and self-sufficient, prefer to play it safe. Lad and Tailor (2016) analysed the stock exchanges in India, finding that ordinary stock investors were unable to capitalize on market development and volatility. Prasad et al. (2017) examined concerning the psychological impact of disposition and overconfidence was identified in the Indian equity market.\n\nSarkar and Sahu (2018) investigated the impact of demographic factors, awareness, and perceived risk attitude on investment behaviours, finding that demographic characteristics, knowledge, and risk perception have a considerable impact on individual stock market investors’ investment behavior. There is a school of thought within behavioural finance theory that maintains investors act irrationally when drawing speculative conclusions (Shantha, 2019). Prospects including risk aversion, loss aversion, mental accounting, and crowding behaviour, as well as heuristics including attachment, gamblers’ misinterpretation bias, and competence bias, inform the resolution generation approach. Ordinarily, private investors acquire stocks during periods of upward trends and divest them during periods of declining trends.\n\nSome factors that have a detrimental impact on the stock market include war crimes, fraud, government instability, attacks, scams, high oil prices, and instability on a global and domestic scale. Accordingly, we choose to investigate the aforementioned connection between psychological and sociological factors. The impact of investors’ irrational, rational, and decision-making behaviours on their perceptions of stock index and market movements is the focus of this research.\n\n\nBackground of the study: Literature review\n\nClassical finance, which is founded upon rational expectations rather than investor sentiment, disregards investor sentiment (Friedman, 1953). The asset pricing model assumes that future cash flows and discount rates determine asset returns. It seems logical that rational arbitrage brings asset values closer to their fundamentals. Smales (2014) examined collective news perception and implied volatility index swings. The implied volatility index negatively correlates with news sentiment. The implied volatility index fluctuates more after unfavourable news. Garg and Varshney (2015) investigated the momentum impact in the Indian equity market from May 2000 to April 2013 utilising significant CNX 500 businesses in four sectors: automobile, banking, pharmaceutical, and Information technology. They found a momentum impact in the Indian stock market, supporting behavioural hypothesis, traders’ underreaction and overreaction, to firm-specific news are other causes of momentum (Daniel et al.,1998; Hong et al., 2000).\n\nAn early inaction and subsequent overreacting to firm-specific news as well as investors’ overconfidence in their capabilities, generate momentum in the stock market (Chan et al., 1996; Hong & Stein, 1999; Hirshleifer, 2001). Market information flow affects asymmetric volatility in four rising market economies: Brazil, Russia, India, and China (Naik & Padhi, 2015). All four nations have statistically significant asymmetric equity return volatility during the research period. Due to a “leverage effect,” negative shocks induce higher market volatility than positive shocks of the same magnitude in these nations. Kumari and Mahakud (2015) experimentally examined investor sentiment and stock return volatility in the Indian stock market. Volatility persists and has clustering, asymmetry, and leverage effects due to investors’ psychological biases and herding tendencies. Thulasipriya (2015) investigated investors’ preferences for various investment channels as well as their investing pattern.\n\nLad and Tailor (2016) examined how India’s stock markets have changed structure, ups and downs, and benchmarks, making them functional. Ordinary stock investors, however, were unable to profit from the market’s growth and volatility. The validity findings showed that investor investment decisions are influenced by behavioural biases. Aruna and Rajashekar (2016) examined the many factors that influence the investment decisions of retail investors. The study indicated that these traits are subject to change throughout time. Researchers concluded that gold outperforms other alternative investments based on a comprehensive analysis of daily gold prices, daily stock index (Nifty50), and daily bond (India Govt.) yield from 2012-2019. Gold investing is safer than stock and bond investment because gold prices have less daily fluctuation (C.V, 2017). An empirical study aimed at identifying differences in investing behavior preference between individual investors in Mainland China and Hong Kong (Mak & Ip, 2017).\n\nProsad et al. (2017) revealed substantial experimental evidence of the disposition consequence and overconfidence in the Indian equity market between 2006 and 2013. Sarkar and Sahu (2018) tested how demographics, awareness, and risk attitude affect investment behaviour. The study found that demographics, expertise, and risk perception influence stock market investors’ behavior. Empirical evidence substantiated the overconfidence hypothesis. Mushinada and Veluri (2018) overconfident investors respond too strongly to confidential information and too softly to disclosures. EGARCH found that when predictions come true, self-attribution bias increases investor confidence and trade volume. Ultimately, the excessive confidence of investors leads to a substantial increase in the volatility of returns due to their active trading. Beer et al. (2018) looked at the possibility that investor insolence impacts European accruals anomalies. The author discovered a correlation between investor psychological state and the mispricing of accruals in European markets. A greater impact was felt on stocks with arbitrary, difficult-to-arbitrage prices. Vidya and Satheesh (2019) examined a variety of behavioural biases, including heuristic bias, optimistic bias, herd biases, loss aversion bias, and overconfidence bias, in order to investigate any relationships between demographic variables and investor behavioural biases. Areiqat et al. (2019) examined the impact of a number of significant behavioural finance variables covered in the financial literature (overconfidence, loss aversion, risk perception, and herding) that may influence the stock investing decision-making at Amman Stock Exchange (ASE), as well as the relative relevance of these variables. Narasimha and Mushinada (2020) proposed that overconfidence displayed the greatest level of relative importance. The researcher further analysed self-attribution bias, overconfidence bias, and investors’ ability to adjust to market fluctuations. Nevertheless, investors sporadically exhibited behavior that seemed ridiculous.\n\nCui and Zhang (2020) examined investor emotion and stock market risk of catastrophe. High-feeling organizations were shown to be more vulnerable to stock price declines. The crash risk was more significantly influenced by investor mood for enterprises that had higher debt ratios, default risks, and analyst forecast dispersion. According to Ye et al. (2020) herding behavior is prevalent in China’s A-share market, especially during periods of extreme bear market conditions, but not during periods of mild bull market conditions. This supports the study hypothesis, which holds that herding behavior is a result of loss aversion and consequential anticipation.\n\nBouteska and Regaieg (2020) investigated the impact of loss aversion and overconfidence on the performance of enterprises in the United States. They initially examined the effects of loss aversion on the economic performance of these organizations. Dhall and Singh (2020) analysed the collective behavior of investors in the business by utilizing NSE data to study herding mentality. The author analysed the phenomenon of herding behavior prior to, during, and following the COVID-19 pandemic. Maghyereh and Abdoh (2022) identified a differentiation between the Global Financial Crisis (GFC) and the COVID-19 crisis in terms of how sentiment information influenced market volatility. Scientists investigate the predictive capacity of emotions during crises as they might reduce ambiguity on the actual fluctuation of assets. The discovery demonstrated that emotion is a more accurate predictor of realized volatility during periods of crisis, contingent upon the kind of asset. Cevik et al. (2022) investigated the relationship between optimistic and pessimistic investor perspectives and stock market returns and volatility in the Group of 20 nations. The Google Search Volume Index was utilized to assess investor opinion toward COVID-19 and its vaccination. During the period from March 2020 to May 2021, the author discovered significant correlations between positive and negative investor sentiments, stock market returns, and market volatility. Specifically, the returns on stocks increase when investors exhibit optimism and decrease when they display pessimism, particularly at lower quantiles. Optimistic investor sentiment decreases market volatility, whereas pessimistic investor sentiment increases market volatility. Several investigations Choudhary and Singhal (2020); S. Kumar et al. (2021); Sahoo and Kumar (2021) and Kartal et al. (2022) have idendified the causal connections between the stock market and the stock market crises. Previous studies He et al. (2020) and Stawiarski (2021) have established a causal connection between India and Asian nations. The GARCH model applied Narasimha and Mushinada (2020) to analyse the sentiments of the investors. It revealed that the Indian stock market exhibited higher levels of volatility compared to industrialized nations throughout the crisis. Recent developments in behavioural economics have revealed the presence of volatility clustering in the Indian stock market. This has been achieved by analysing time series data and employing predictive modelling techniques to understand investor behaviour. Experimental results by Khaing et al. (2020) revealed that trend extraction with additional criteria of news effect curve on stock extracted more trends during the crisis. In addition to new factors, the stock trend extraction conclusions are more consistent with actual stock price movement. Chen (2021) constructed an innovative neural network model to enhance the forecasting capabilities and emotional analysis of investors. Belciug et al. (2021) tested a quantitative and statistical concept based on a competitive/collaborative method to predict a prospective stock market transaction price for a security while an economic upsurge.\n\nBiswas et al. (2021) analysed the models and techniques employed for predicting stock market price fluctuations. They focused on the advantages and disadvantages of these approaches, particularly in the context of a crisis. Debata et al. (2018) identified a positive (negative) correlation between investor sentiment and liquidity (illiquidity). Results also revealed that the sentiment of international investors has a major impact on the liquidity of emerging stock markets. Cheema et al. (2020) discovered a favourable correlation between emotion throughout the bubble phase and market returns, which becomes unimportant once the bubble bursts. Investors view increased indebtedness in the energy sector and higher operating income in the telecom sector as predictors of future economic instability and worsening the condition, according to the results of a partial least squares regression model for consumer confidence. On the other hand, there was a positive relationship between the stock index and consumer confidence (Zorio-Grima & Merello, 2020). Investors are emotionally susceptible. Due to Australia’s status as a resource-rich but capital-poor nation, this article analyses and evaluates the influence of investor mood on performance returns. Consumer Confidence Index (CCI) and trade volume are sentiment proxies used to examine aggregate, cross-sectional, and predictive regression impacts while controlling for macroeconomic variables (Banchit et al., 2020). Haroon and Rizvi (2020) examined the association between the mood of investors as influenced by COVID-19-related media reports and the volatility of stock markets. According to the conclusions of the study, the rise in uncertainty and volatility on the financial and stock markets was a result of news related to COVID-19. Ambros et al. (2021) analysed the influence of COVID-19-related news on eight distinct stock market indices. Even if stock returns were unaffected through changes in the dimensions of COVID-19-related news, their empirical findings indicate that the volatility of European stock markets rose dramatically as a result of the increase in COVID-19-related news coverage. Iyke and Ho (2021) analysed Google search phrases pertaining to COVID-19 to gauge investor interest, and then analysed the association between investor attention and stock market indexes in 14 African nations. Researchers concluded that investor attention is one of the most influential determinants of stock returns, and that a rise in investor attention is associated with a fall in stock returns in Botswana, Nigeria, and Zambia. In both Ghana and Tanzania, investor sentiment and the returns on stock investments exhibit a favourable link. Narayan et al. (2021) developed six distinct global sentiment indicators for COVID-19 based on a word search of 45 major media pieces. These variables include COVID, medical, vaccine, travel, ambiguity, and collective sentiment. These signs were useful for analysing the effects of the global pandemic, according to the conclusions of the research. Prior to 2012, the unpredictability of economic policy had a clear and provable adverse impact not just on investor sentiment but also on the short-term stability of the financial system, with the impact on investor sentiment being far bigger than that on the financial system. These impacts began to come to the forefront in 2008, which was right in the thick of the global financial crisis. Additionally, investor optimism had a favourable and steadily expanding influence on financial stability up to the year 2010, after which the beneficial effect gradually vanished (Qi et al., 2022). The researcher found that style returns have predictive power for future stock returns during moments of elevated sentiment, but not during periods of low sentiment (Ashour et al., 2022).\n\nLi and Xing (2023) studied the relationship between sentiment and synchronicity in the Chinese stock market, discovered that investor sentiment had a considerable positive effect on the synchronisation of stock returns. Liu et al. (2024) demonstrated that coal price fluctuations have a considerable negative influence on Chinese stock market returns, but the resultant degree varies over time, notably amid recessions. According to research, investor psychology impacts the capital market’s performance and the manner in which investors interpret basic data, which in turn impacts the correlation between these two variables and stock returns (Fonou-dombeu et al., 2024). Researchers (Gao et al., 2024) indicates that both trading and online emotions have a detrimental impression on stock returns through the mediating result of liquidity. The results of a comparison between the partial least squares (PLS)-based investor sentiment index, three linked sentiment metrics from prior research, and six separate sentiment proxies showed that performed the best in predicting stock volatility on the Chinese stock market (Song et al., 2023). There is a negative contemporaneous link between investor sentiment and market return, according to research on the function of investors in the stock market (Phan et al., 2023). Ayinuola and Adetiloye (2023) discovered that the sentiment index is adversely and strongly related to stock return volatility. Additionally, good emotion has a larger disproportionate effect on the volatility of market returns than negative sentiment. While numerous studies have significantly advanced our understanding of the optimal and actual stock market behaviour of investors, as well as the impact of such behaviour on the decision-making process, they fail to provide a comprehensive picture of the interrelationships between traditional finance principles and investors’ perspectives on the performance of stock market indices. Furthermore, they fail to examine how rational and irrational investors influence the performance of stock market indices. Therefore, an innovative and very reliable aspect of the financial markets can be studied by investigating investor behaviour through the prism of a modern social and psychological component.\n\n\nMethods\n\nIndividual investors who invested in the Indian stock market through stock brokerage firms in India comprise the study’s population. All of the investors are drawn from various cities with a high concentration of retail investors. When the population being sampled is exceptionally large, it becomes extremely difficult to design a sampling frame. Even though the population of India’s individual investors who invest in equity shares is extremely large and difficult to identify, it is challenging to design a sample frame for this group. Nevertheless, we developed a sample frame based on data from the Stock Holding Corporation of India Ltd. The investigated population was chosen arbitrarily in advance based on trading and consultation with professionals from Stock Holding Corporation of India Ltd. Samples were collected using stratified random sampling. Stratified random sampling is a form of confined probability sampling in which the population has been split into strata based on their homogeneity, and observations are randomly selected from all of the strata. The response rate of investors was 81.5%, which means that out of the 800 online surveys that were mailed out, only 571 were filled out and answered. Out of 571 accurately filled up questionnaires, 552 were utilised for analysis. Geographic location was the most relevant criterion for stratifying the whole universe, according to the study. Based on this, the geographical structure of India may be separated into five subregions: the northern area, the eastern region, the central region, the western region, and the southern region. The questionnaire’s final objective is to analyse the behaviour of retail investors. In this section, data were gathered using a 5-point Likert scale, where “1” indicates Strongly Disagree, “2” indicates Disagree, “3” indicates Neutral, and “4” indicates Agree. “5” indicates Strong Agree. Cronbach’s Alpha is the most common and extensively used reliability measure.\n\n\nHypothesis\n\n\n\nThere is no association between factors (behavioural biases variables) and investors decision making.\n\nThere is an association between factors (behavioural biases variables) and investors decision making.\n\n\nReliability and validity of the data\n\nWe collected a sample of 552 investors, which is bigger than 300. As a result, the Shapiro-Wilk test is performed to evaluate the normality of Table 3, which shows that the data has a normal distribution. The alpha coefficients of 0.726 and 0.831 suggest a rather high level of internal consistency among the 33 items (Table 1 and Table 2). A dependability coefficient of 0.70 or above is considered “acceptable” in most social science research situations.\n\nA descriptive and inferential analysis was conducted on all valid responses to the survey. In order to conduct a descriptive analysis, SPSS 20.0 was used. In accordance with Anderson and Garbing’s (1988) recommendation, a structural equation modelling (SEM) approach was used, and a confirmatory factor analysis was performed to assess validity of latent components, followed by a SEM analysis for hypothesis testing. This study mainly utilized the structural equation modelling (SEM) approach for two reasons: firstly, it offers a systematic way to evaluate construct-indicator linkages and model relationships within a single model (Hair Jr et al., 2017; Narasimha & Mushinada, 2020) and secondly, it provides robust and in-depth statistical approaches for dealing with financial models.\n\n\nKMO and Bartlett’s Test\n\nThe KMO value presented in Table 4 indicates that factor analysis is a suitable approach for the given data. Furthermore, based on the aforementioned information, the fact that the significance value is below 0.05 indicates a substantial correlation between the chosen elements in the study. The Bartlett’s Test of Sphericity has a p-value of 0.000, indicating its high statistical significance. This meets the requirement to reject the null hypothesis. It indicates that there is a good correlation between the variables, which allows for further study.\n\n\nConfirmatory factor analysis for social factors (market inefficiency)\n\nIn this study, the confirmatory analysis (CFA) is used to quantitatively evaluate validity and reliability (Henseler, Ringle, & Sinkovics, 2009). It is often assumed and acknowledged that an item’s individual dependability is adequate if its factor loading for its primary dimensions surpasses 0.60 (Chin et al., 1997). Hair, Black, Babb, and Anderson (2010) quantified composite reliability (CR) by summing the squared factor loading and error variance of each construct. This enabled them to demonstrate that the constructions are sufficiently dependable. CR, like Cronbach’s alpha, shares the advantage of assuming equal weighting for each item in the composite load determinants, without considering the actual component loadings (Lin & Lee, 2004). Convergent validity testing involves assessing the relationship between constructs to discover if they are indeed connected. This evaluation focuses on constructs that are thought to have a connection. In contrast, discriminant validity facilitates the demonstration of the validity of constructs by establishing the absence of any association between the constructs under investigation.\n\nIt basically verifies that constructs that are not meant to be connected are not related. The overall reliability is CR > 0.70, CR > AVE, and AVE > 0.50. In the case of discriminant validity, these values should be present. MSV AVE, and the square of AVE, that is, the diagonal value, must be larger than the vertical value.\n\nAccording to the established criteria, a coefficient of reliability (CR) estimates of 0.70 or greater indicates excellent reliability and demonstrates robust internal consistency (Hair et al., 2010). The composite reliability analysis ( Table 5) indicates that the assessment of all the constructs lies within the range of 0.764 to 0.863. The range exceeds the minimum requirement of 0.70, suggesting that all the metrics consistently reflect the same underlying mechanisms. The Table 5 further demonstrates the convergence validity of latent components. This study investigates the AVE (average variance extraction) values that are equal to or more than 0.50 in order to meet this criterion.\n\nThe AVE was calculated by utilizing the sum of squared multiple correlations and the count of item (variables) in each comparison. All constructs had satisfactory convergent validity, as shown by their convergent validity ratings of 0.50 or above ( Table 5).\n\nThe study employs a structural model to assess the hypothesized correlation between behavioural traits and the decision-making of individual investors. The hypothesized structural equation model was analysed to examine the goodness of fit indices and other factors related to the presented hypotheses ( Figure 1). The model fit indices presented in Table 5 indicate that the predicted structural model provides a reasonable match to the data. During the initial round of assessing fitness, the p value was found to be 0.00, indicating an exceptional degree of fitness. However, more measures were required to determine the precise fitness levels. Figure 1 illustrates the association between dependent and independent variables as indicated by the structural model.\n\nThe Table 6 above presents the model fit value for the CFA. The CMIN value of 4.022 is suitable. Yes, a GFI value of 0.947 is considered appropriate for the model. The CFI has a value of 0.966, which is considered acceptable as it above the value of GFI. The NFI result of 0.932 aligns with the model. The RMSEA value is 0.060, indicating an appropriate level. Hence, the model is a good fit.\n\nThis study employed a structural model to assess the hypothesized correlation between socioeconomic variables and the investment choices made by individual investors. Various indications of goodness of fit are observed for the specified hypotheses in the structural model depicted in Figure 2, with a focus on exploring the parameters. Table 7 displays the findings of the model fit indices, indicating that the suggested structural model effectively explains a strong correlation between statistical and social variables. Therefore, the null hypothesis has been rejected.\n\nTable 8 illustrates the correlation between factors contributing to market inefficiency and the process of decision making. The study found that Information Search, Price Anchoring, Herding Behaviour, and CBDC had significant impacts, with β coefficients of 1.73 (p = 0.017), -0.318 (p = 0.023), 6.345 (p = 0.030), and -0.464 (p = 0.012) respectively. In each example, the value of P is below 0.05, showing a statistically significant link. Hence, social influences exert influence on investors’ decision-making process.\n\n\nConfirmatory factor analysis for psychological factors\n\nThe findings regarding composite reliability, as presented in Table 9, indicate that the evaluation of all constructs varies between 0.712 and 0.778. This significantly surpasses the minimum threshold of 0.70 and signifies that all measures consistently capture the same latent constituencies as it is reflected in Figure 3. The Table 9 demonstrates the convergent validity of latent variables. AVE scores equal to or greater than 0.50. Sarstedt et al. (2014) examined for this study in order to meet this criterion. Investors often lack widespread logic while making investment judgments. The outcomes of the current investigation corroborated this concept. Investors’ financial behaviour is determined by their cognitive capacity to understand all pertinent facts. Their choice of investing opportunities and assets is impacted by their preexisting views, previous experiences, and market trends. Rather of scrutinizing existing information, investors solicit guidance from acquaintances, coworkers, and brokers. Investors admit that their financial decisions are impacted by emotions and ambitions. Gaining a comprehensive understanding of various behavioural biases is crucial for managing and mitigating these biases, hence improving investment performance.\n\nTable 10 above displays the model fit value for the CFA. The CMIN score of 2.021 is acceptable. Indeed, the GFI value of 0.947 is appropriate for the model. CFI has a value of 0.974, which is acceptable because it is larger than GFI. The NFI value of 0.918 agrees with the model. The RMSEA value is 0.069, which is satisfactory. Thus, the model fits flawlessly.\n\nIn addition to these important findings, this study shows that Indian investors are not completely rational and that the country’s marketplaces are inefficient. The association between these findings and the investors’ decision-making process was evaluated empirically by interviewing the investors.\n\n\nFindings\n\nTables 11 and 12 illustrates the correlation amongst behavioural biases and financial decision making. The effects of overconfidence, loss aversion, representativeness, gambler’s fallacy, and regret aversion the values of β and p for the given data are as follows: β = 0.534 with p = 0.036, β = 0.202 with p = 0.003, β = 0.071 with p = 0.047, and β = -0.249 with p = 0.024. The P value in each example is below 0.05, showing a statistically significant link. Hence, psychological elements exert influence on investors’ decision-making process (Figure 4). With respect to the dependent and independent variables, Table 12 presents the outcomes of the structural model. Cognitive biases include overconfidence, loss aversion, representativeness, the gambler’s fallacy, and regret aversion affect investors’ decisions. The results of the research indicate that individual stock market participants in India employ implicit biases to accelerate their decision-making when influenced by behavioural biases. This study’s results suggest that behavioural biases have a substantial influence on the decision-making process of Indian investors. Regarding social impact, herding has been identified as a very important factor, indicating that investors tend to imitate the investment behaviours of their peer groups.\n\nThis study confirms the results of Chen, Rui, and Xu (2003), who demonstrated that the phenomenon of herd behaviour is more widespread in developing markets compared to developed market. An investor’s decision-making process is impacted by many psychological biases, such as overconfidence, loss aversion, representativeness, the gambler’s fallacy, and regret aversion. According to the results, Indian investors are highly influenced by their own behavioural biases when making investment decisions. One of the most powerful forms of social influence is herding, which means that people tend to mimic the investment strategies used by their friends and colleagues. The results of this study corroborate those of Chen, Rui, and Xu (2003), who demonstrated that emerging economies have a greater herding effect compared to industrialized nations.\n\n\nConclusion\n\nAlthough risk and return are commonly used to evaluate investment performance, this metric does not consistently demonstrate its ability to anticipate financial returns and investment choices for investors. While classical theories may not always accurately predict market conditions, it is appropriate to acknowledge the significance of behavioural biases in investment decision-making. Our findings are consistent with the previous research based upon the investors decision making factors (Raut et al., 2018). The main aim of this study is to determine the importance of socio-psychological factors in affecting the decision-making behaviour of individual investors.\n\nIn order to make rational investing decisions, this study shows which socio-psychological biases are most common. Based on the results of this study, it is critical for fund managers to be able to identify and avoid making the same mistakes again when it comes to monitoring. Therefore, fund managers should utilize a flexible investing approach in an intricate market system where individual emotions have a substantial impact on developing an effective portfolio. This study provides useful insight into the most prevalent socio-psychological factor that should be considered by investors when determining a suitable portfolio level. From a management perspective, it is imperative that fund managers possess the ability to identify and avoid reiterating common behavioural mistakes, as indicated by the study’s results. These implications can provide guidance to investment advisors, regulators, and other players in the market, as well as to individual investors, prompting them to reflect on their investment-making choices throughout different time periods.\n\nThus, fund managers should employ an adoptive investing approach in a complex market system where the emotions of individuals play a significant part when constructing an optimal portfolio. The study’s conclusions demonstrate that behavioural biases significantly affect Indian investors’ ability to make decisions.\n\nFuture research can examine scenarios or surroundings in which investor-specific factors, such as the behavioural finance approach, dominate one another. Researchers can also analyse the predominant market-related drivers that have the biggest influence on investor mood across time, in different scenarios, and within various country contexts. The limited influence of macroeconomic fundamentals and policy changes may also be a compelling subject for future scholars to investigate.\n\nThis research adhered to the criteria set by the Uttaranchal University Research Ethics Board (REB), which granted ethics approval under number UU/DRI/EC/2024/007 (18th Sept. 2024). The formal approval letter was issued retroactively. In July 2024, we obtained verbal permission from the REB to commence our study, as written approval is provided only when requested by a journal. The REB reviewed our comprehensive application, confirming that we met all ethical norms and regulations before granting preliminary verbal consent. Consequently, we initiated our investigation in good faith, fully aligned with the ethical standards outlined in the preliminary review.\n\nThe questionnaire was submitted to the REB of the university, where board members and the chairperson assessed the viability of the research topic. After all members presented their research objectives, the questionnaire was approved for conducting the study.\n\nAll of the study’s participants have provided written informed consent. A self-explanatory written statement was included with the questionnaire for participants, and a similar questionnaire was submitted to the University research board.",
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}
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[
{
"id": "345427",
"date": "27 Dec 2024",
"name": "Dipendra Karki",
"expertise": [
"Reviewer Expertise My area of expertise is finance",
"with a special emphasis on stock market research",
"investing methods",
"and financial economics",
"particularly behavioral finance."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview Report\nManuscript Title: Decoding Investor Sentiments in the Indian Stock Market: A Structural Equation Modelling Approach\nAbstract/Introduction:\nThe study primarily aims to analyse the impact of social biases and psychological bases on investors’ decision-making. However, the proxy variables for the latent factor, 'social biases,’ are not found sufficient to capture the social context. It seems the study has used information search (IS), Price Anchoring (PA), Heuristic Behavior (HB), & CBDC as the proxy for social factors, which the theory doesn’t support. They rather fall in the behavioural domain. It is required to include the theoretical bases for considering those factors as social biases in the study.\n\nFurther, the study develops only one hypothesis related to psychological (behavioural) biases and decision-making, missing to address the social biases. Though it showed that both hypotheses were tested. This brings significant discrepancy with the study objectives.\nNeed to identify the main research issues and problems and mention how this study addresses these problems.\nThough it addresses some highly interesting issues, highlighting the limitations of this study would be better to hint the future researchers, giving further scope of the study in this area.\nThe last paragraph is expected to discuss about the organization of the study. How the subsequent sections have been arranged to make readers acquainted with the flow of the study.\nLiterature Review: The literature on social factors is not sufficiently reviewed to establish the validity of employed observed variable ‘information seeking’ as mostly the reviews are made on psychological factors.\nSome citations, such as (C.V, 2017) are not included in the reference/bibliography list, making it difficult to verify the sources or their relevance.\nAdditionally, few in-text citations [e.g., S. Kumar et al. (2021) …] are not cited in APA format properly; for example, Kumar, S., Choudhary, S., Singh, G., et al. (2021) are to be cited as Kumar et al. (2021) or, if it is Sahoo, S., and Kumar, S. (2021), to be cited as Sahoo and Kumar (2021).\nResearch Methods:\nIt is unclear how the study identifies the heterogeneity among different investor groups and how the strata are formed to choose the sample investors randomly. It requires justification and details on the process of sampling.\nAnalysis that relies on respondents’ perceptions collected through the online survey requires cross-validation by collecting some data by visiting to the respondents in person by field survey. So that the study may establish the results' validation and authenticity.\nThe study only tested one and only one hypothesis related to psychological biases. It should address the issue of missing out of social biases by formulating the second hypothesis.\n\nTable 1 and Table 2 should present the alpha values for each factor of social and psychological biases rather than including all measured variables (33 & 25) at once. I don’t know how the author is presenting social and psychological biases with equal 350 d.f. in the Shapiro-Wilk Test (Table 3).\n\nBefore moving to confirmatory factor analysis (CFA) using SEM, it is required to extract the only relevant factors of the above two types of biases employing exploratory factor analysis (EFA).\nResults:\nThe study's analysis includes two estimating models that go beyond the hypothesis, raising doubt in the analysis. Again, the first estimating model represents IS, PA, HB, and CBDC as social factors beyond their nature. Furthermore, the second model estimates overconfidence, loss aversion, representativeness, gamblers fallacy, and regret aversion as psychological factors that were not separately identified in the alpha test or derived by EFA.\nConclusion:\nThe result sounds good, but it lacks discussion on the inherent limitations and delimitations of the study so as to bring robustness to the findings and illustrate the future scope of the study.\nThe conclusion drawn primarily seems biased by discussing only the favored variables and not supported by the findings. The findings of the study show statistical significance to all the study variables.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "13032",
"date": "28 Dec 2024",
"name": "FARMAN ALI",
"role": "Author Response",
"response": "I will be incorporating all the suggestions.Once I get the access to modify it."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1378
|
https://f1000research.com/articles/13-1377/v1
|
18 Nov 24
|
{
"type": "Systematic Review",
"title": "Systematic review of mitigation approaches in Ethiopia's energy sector: Strategies for sustainable development and climate resilience",
"authors": [
"Tofikk Redi"
],
"abstract": "Abstract The global energy sector is a primary contributor to greenhouse gas (GHG) emissions, predominantly through fossil fuel combustion for electricity, heating, and transportation (IEA, 2021). This study systematically reviews Ethiopia’s energy sector mitigation approaches, focusing on renewable energy strategies and energy efficiency initiatives. While Ethiopia has made significant progress in hydropower, accounting for over 90% of its electricity generation, challenges remain in diversifying its energy mix to include geothermal and wind energy (Ethiopian Ministry of Water, Irrigation, and Energy (2019) and African Development Bank, 2020). The Climate Resilient Green Economy (CRGE) strategy sets ambitious targets for achieving carbon neutrality by 2030, challenges remain in diversifying its energy mix to include geothermal and wind energy (Benti, Woldegiyorgis, et al., 2023 and Federal Democratic Republic of Ethiopia, 2011), yet its implementation faces barriers, including financial constraints, technological gaps, and weak institutional capacity (Silitonga et al., 2020). The study highlights the potential of Ethiopia’s vast renewable energy resources, such as geothermal and wind, to enhance energy security and foster economic growth through job creation. Despite the hurdles, opportunities exist for scaling up mitigation efforts, particularly through public-private partnerships and improved policy frameworks. This review underscores the importance of addressing barriers to achieve a sustainable energy transition in Ethiopia, contributing to local and global climate mitigation goals. Thus, the policymakers should boost investments in solar, wind, and geothermal energy, reduce reliance on hydropower through incentives, and establish an inter-agency task force for policy alignment. And also, exploring green bonds and fostering human capital development through training and partnerships are essential. A strong monitoring and evaluation framework is crucial for tracking progress towards energy sustainability goals.",
"keywords": [
"Mitigation Approaches",
"Energy Sector",
"Sustainable Development",
"Climate Resilience",
"Ethiopia"
],
"content": "Introduction\n\nThe global energy sector is a dominant source of greenhouse gas (GHG) emissions, contributing approximately 73% of total global emissions, largely due to the burning of fossil fuels for electricity, heat, and transportation (IEA, 2021). This reliance on fossil fuels exacerbates global warming, necessitating urgent action to mitigate emissions from the energy sector. The Paris Agreement, adopted in 2015, underscores the need for all countries to implement strategies aimed at limiting global temperature rise to below 2°C above pre-industrial levels (UNFCCC, 2015b). To achieve this, countries must transition to low-carbon technologies, enhance energy efficiency, and promote renewable energy sources (Lo & Castán Broto, 2019). Understanding direct and indirect energy use is key to crafting effective policies that reduce energy consumption and CO2 emissions, fostering household energy efficiency and sustainability (Andrews-Speed and Zhang, 2019). From global climate initiatives to accelerate the development of renewable energy projects, highlighting key challenges and opportunities for attracting investments (Negash et al., 2021).\n\nAt the regional level, Africa’s energy sector faces a dual challenge: expanding energy access to underserved populations while reducing GHG emissions. The continent is home to vast untapped renewable energy resources, including solar, wind, and hydropower, which hold the potential to drive sustainable development and mitigate climate change (IRENA, 2020). Despite these resources, Africa’s energy infrastructure remains heavily reliant on fossil fuels, particularly in North Africa and parts of Sub-Saharan Africa (Lahnaoui et al., 2024). While Africa contributes only about 4% of global GHG emissions, it remains disproportionately vulnerable to climate change impacts, underscoring the need for robust energy sector mitigation strategies (IPCC, 2022). In Africa, focusing on challenges like limited access, financial constraints, and policy gaps. They propose solutions such as regional cooperation, increased investments, and technology transfer to enhance energy access and sustainability (Karekezi & Kithyoma, 2021).\n\nIn Sub-Saharan Africa, the energy mix is dominated by traditional biomass, with nearly 80% of households relying on wood, charcoal, and other forms of biomass for cooking (Hoffmann et al., 2015). This heavy dependence on biomass fuels has contributed to deforestation and indoor air pollution, posing significant health and environmental challenges (World Bank, 2022). However, several countries are making efforts to transition to cleaner energy sources. For instance, Kenya has made notable advancements in geothermal energy development, and South Africa has been scaling up its solar and wind energy capacities (Takase et al., 2021). Despite these positive developments, the region faces challenges related to financing, policy implementation, and infrastructure constraints, which continue to slow down the transition to renewable energy (IRENA, 2021). The potential of renewable technologies like solar, wind, and biomass to improve energy access in remote areas, emphasizing the need for supportive policies, financing models, and community involvement for successful implementation (Kammen and Kirubi, 2021).\n\nIn East Africa, the potential for renewable energy is considerable, particularly in geothermal energy in Kenya and Ethiopia, and hydropower in Uganda and Tanzania (AfDB, 2020). Ethiopia, for example, holds significant geothermal reserves, which, if fully developed, could reduce the country’s reliance on hydropower and provide a more reliable energy source (Benti, Woldegiyorgis, et al., 2023b) However, the adoption of renewable energy in the region remains limited due to high initial capital costs, lack of technical expertise, and weak institutional frameworks. Efforts are underway to address these gaps through public-private partnerships and revisions to national energy policies aimed at encouraging clean energy investments (AfDB, 2020). Countries with significant geothermal potential, like Kenya, are increasingly shifting to renewable energy sources, driven by the economic and environmental benefits of geothermal energy for sustainable development (Ondraczek, 2021).\n\nEthiopia is a notable case, as the country has set ambitious targets under its Climate Resilient Green Economy (CRGE) strategy, which was launched in 2011. The CRGE aims to achieve middle-income status by 2025 while keeping GHG emissions low (Federal Democratic Republic of Ethiopia, 2011). Ethiopia’s energy sector has made significant progress in hydropower, which accounts for over 90% of its electricity generation (Tiruye et al., 2021). Additionally, the country is actively exploring other renewable energy sources, such as wind and geothermal, to diversify its energy portfolio (Benti, Woldegiyorgis, et al., 2023b). However, challenges remain, particularly in extending access to clean energy in rural areas, integrating renewable sources into the national grid, and securing sufficient financing for large-scale renewable projects (World Bank, 2022). Overcoming these obstacles will be crucial for Ethiopia to meet its national climate targets and ensure energy security in the coming decades.\n\nTo systematically review and assess the mitigation approaches in Ethiopia’s energy sector, focusing on strategies that promote sustainable development, reduce greenhouse gas emissions, and enhance climate resilience.\n\n\n\n1. Evaluate existing mitigation strategies effectiveness employed in Ethiopia’s energy sector, including renewable energy projects, energy efficiency initiatives, and policy frameworks.\n\n2. Assess the environmental and economic impacts of the implemented mitigation approaches, particularly in terms of emission reductions, energy security, and job creation.\n\n3. Identify barriers and challenges faced in the implementation of energy sector mitigation strategies, including technological, financial, and institutional obstacles.\n\n4. Evaluate the impact of current policies on the success of mitigation approaches and recommend policy enhancements.\n\n5. Identify potential areas for improvement and future opportunities for scaling successful mitigation approaches in the Ethiopian energy sector.\n\n6. Provide recommendations for strengthening Ethiopia’s energy sector mitigation efforts, with a focus on scalability, financing mechanisms, and integration with national climate change goals.\n\n\nMethod\n\nThis systematic review has follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure a comprehensive, transparent, and standardized approach to the identification, selection, and synthesis of relevant studies on mitigation approaches in Ethiopia’s energy sector. The review has involve four key stages: identification, screening, eligibility, and inclusion.\n\nA systematic search of relevant literature has been conducted across multiple databases, including Google Scholar, Scopus, Web of Science, and JSTOR, to identify peer-reviewed articles, government reports, and significant grey literature. The search strategy has been developed using specific keywords such as Ethiopia energy sector mitigation, renewable energy Ethiopia, energy efficiency Ethiopia, and policy frameworks in the energy sector. No date restrictions will be applied, though the focus has on literature from 2010 onward to capture current mitigation strategies.\n\nTitles and abstracts of studies has been reviewed, and those not meeting predefined inclusion criteria will be excluded. The inclusion criteria has focus on studies that examine mitigation approaches in Ethiopia’s energy sector, assess renewable energy or energy efficiency strategies, and discuss policy frameworks or financial mechanisms. The review has include peer-reviewed articles, government reports, and relevant grey literature. Excluded studies has include non-peer-reviewed sources (except significant grey literature) and those not directly addressing the energy sector in Ethiopia.\n\nFull texts of the remaining studies has then be thoroughly reviewed to assess their eligibility based on detailed criteria. Eligible studies has been those that contain original data on mitigation strategies, provide quantitative or qualitative evaluations of these approaches, discuss barriers and facilitators to implementation, or include case studies with regional or national relevance to energy mitigation in Ethiopia.\n\nThe final synthesis has group studies into key thematic areas such as renewable energy, energy efficiency, policy frameworks, and financial mechanisms. Data from each study have been extracted and organized, interpret and discussed into a structured way, capturing essential information such as study objectives, mitigation approaches, effectiveness, barriers, and future opportunities. A standardized data extraction form have been used to ensure consistency across all studies. The extracted data has include study design, location, mitigation strategies employed, outcomes assessed, and policy recommendations.\n\nThe findings have been synthesized using a narrative approach, focusing on key trends, implementation barriers, facilitators, and future opportunities. Where possible, quantitative results has been summarized and compared across studies to highlight the effectiveness of mitigation approaches and their alignment with Ethiopia’s national and international energy policies. For a concise summary of the method, refer to the systematic review flowchart in Table 1 and the checklist in Table 2. These tables provide a structured overview of the review process, detailing each step from the initial literature search to data extraction and synthesis. The flowchart ( Table 1) visualizes the process, highlighting key stages like study identification, screening, eligibility assessment, and inclusion criteria. Meanwhile, the checklist ( Table 2) ensures a comprehensive review, covering essential criteria such as study selection, data management, quality assessment, and reporting standards.\n\n\n\n- Conduct a literature search using Google Scholar, Scopus, Web of Science, JSTOR.\n\n- Use keywords like Ethiopia energy sector mitigation, renewable energy Ethiopia, energy efficiency Ethiopia.\n\n\n\n- Review titles and abstracts.\n\n- Apply inclusion criteria (focus on mitigation in Ethiopia's energy sector, peer-reviewed studies, etc.).\n\n- Exclude studies not meeting these criteria.\n\n\n\n- Retrieve and assess full texts.\n\n- Evaluate based on detailed criteria, such as original data on mitigation strategies, relevance to Ethiopia, and discussion of policy frameworks.\n\n\n\n- Extract relevant data using a standardized form.\n\n- Group studies into thematic areas: renewable energy, energy efficiency, policy frameworks, and financial mechanisms.\n\n\n\n- Capture key information: study objectives, methodologies, mitigation approaches, effectiveness, barriers, facilitators, and recommendations.\n\n\n\n- Synthesize findings narratively.\n\n- Compare quantitative results across studies to assess alignment with national and international policies.\n\n\n\n- Report findings in a structured format using tables and figures.\n\n- Highlight trends, implementation barriers, and future opportunities for energy sector mitigation strategies.\n\n\nResult and discussion\n\nRenewable energy\n\nRenewable energy projects\n\nEthiopia has made significant strides in harnessing renewable energy, particularly through hydropower, which accounts for over 90% of the country’s electricity generation (IRENA, 2021). The Grand Ethiopian Renaissance Dam (GERD), with an expected capacity of over 6,000 MW, stands as the flagship project aimed at providing clean energy domestically and for export to neighboring countries (World Bank, 2022). GERD’s completion is projected to reduce reliance on fossil fuels and enhance energy access in Ethiopia and the region.\n\nDespite the success in hydropower, Ethiopia faces challenges in diversifying its renewable energy portfolio. Geothermal energy remains largely underutilized, with only a few projects like the Aluto-Langano Geothermal Power Plant, which has a capacity of 7.3 MW (African Development Bank, 2020). Wind energy also holds potential, demonstrated by the Ashegoda Wind Farm with a 120 MW capacity, though more investments are needed in this area to balance the dependence on hydropower, especially given the vulnerability of hydropower to climate variability (IRENA, 2020). Renewable energy potential, emphasizing hydropower, wind, solar, and geothermal resources, while identifying challenges like infrastructure gaps, financial constraints, and policy issues. The study highlights the need for investments and strong policies to harness these resources effectively (Hailemariam, 2020).\n\nEffectiveness: Ethiopia’s renewable energy projects have proven effective in expanding electricity access, with a goal of achieving universal electrification by 2025. However, the heavy reliance on hydropower, combined with the underdevelopment of geothermal and wind resources, presents a challenge in ensuring energy security, especially under changing climate conditions.\n\nEnergy efficiency is a critical component of Ethiopia’s mitigation strategy, though its implementation has lagged behind renewable energy projects. The National Energy Efficiency Program focuses on improving energy use in industries, transport, and households (Ethiopian Ministry of Water, Irrigation, and Energy, 2019). Initiatives like the distribution of efficient cookstoves have been promoted to reduce biomass use, which accounts for over 85% of total energy consumption in Ethiopia, and to curb indoor air pollution (World Bank, 2022).\n\nThe Improved Biomass Cookstoves Program, for example, has aimed to distribute 9 million cookstoves by 2030, focusing on rural areas where reliance on traditional fuels is highest (Global Alliance for Clean Cookstoves, 2019). These cookstoves are designed to reduce fuel consumption by 30–50%, decreasing deforestation and lowering GHG emissions. However, adoption rates have been slower than anticipated due to affordability issues and a lack of awareness about the benefits of the technology (SNV, 2021).\n\nIn the industrial sector, Ethiopia has introduced energy audits and incentives for energy-efficient technologies, especially in the cement and textile industries, which are among the highest energy consumers (Mondal et al., 2018) widespread implementation of energy efficiency measures remains constrained by a lack of technical capacity and financing. Strategies to improve energy efficiency in Ethiopia’s industrial sector. It emphasizes the adoption of energy-efficient technologies, capacity building, and policy frameworks to reduce energy consumption, lower production costs, and enhance sustainability in industrial operations ( GIZ, 2020).\n\nEffectiveness: The energy efficiency initiatives, particularly in the household and industrial sectors, show promise but have been hampered by low adoption rates and insufficient financial support. There is significant potential for improving energy efficiency across the economy, but the programs need scaling up and more robust enforcement mechanisms to maximize their impact.\n\nEthiopia’s Climate Resilient Green Economy (CRGE) strategy, launched in 2011, is the cornerstone of the country’s policy framework for climate mitigation. The CRGE envisions a carbon-neutral economy by 2030, with energy sector decarbonization at its heart (Federal Democratic Republic of Ethiopia, 2011). This strategy outlines the expansion of renewable energy, the promotion of energy efficiency, and the establishment of a green economy.\n\nEthiopia has also developed the National Electrification Program 2.0 (NEP 2.0), which aims to achieve universal electricity access by 2025, with 35% of this target to be met through off-grid renewable energy solutions (World Bank, 2022). This aligns with Ethiopia’s focus on rural electrification, where over 50 million people currently lack access to modern energy services. The promotion of mini-grids and solar home systems in off-grid areas has been a key component of NEP 2.0 (USAID, 2021).\n\nIn addition to national strategies, Ethiopia is a signatory to international climate agreements, including the Paris Agreement. The country has committed to reducing GHG emissions by 64% below the business-as-usual scenario by 2030, with a significant portion of these reductions expected to come from the energy sector (UNFCCC, 2015b).\n\nHowever, the implementation of these policies faces several challenges. Limited financial resources, institutional capacity gaps, and external factors such as political instability and climate shocks have hindered the full realization of these strategies (World Resources Institute, 2020).\n\nEffectiveness: Ethiopia’s policy frameworks, particularly the CRGE and NEP 2.0, are ambitious and well-structured, aligning with global climate goals. However, their effectiveness has been constrained by challenges in implementation, including resource limitations, technical expertise, and institutional capacity.\n\nEmission reductions\n\nEthiopia has made significant strides in reducing greenhouse gas (GHG) emissions through its focus on renewable energy, primarily hydropower. The country’s Climate Resilient Green Economy (CRGE) strategy, launched in 2011, sets ambitious goals to limit emissions while fostering economic growth. Hydropower, which accounts for over 90% of Ethiopia’s electricity generation, has played a key role in reducing reliance on fossil fuels, thus mitigating carbon emissions (Federal Democratic Republic of Ethiopia, 2011). The Grand Ethiopian Renaissance Dam (GERD), once fully operational, is expected to further reduce emissions by displacing the need for thermal power plants and cutting GHG emissions by approximately 10.9 million tons of CO2 equivalent annually (World Bank, 2022). Ethiopia’s commitments to reducing greenhouse gas emissions, focusing on renewable energy expansion, reforestation, and sustainable agriculture. It also highlights the country’s adaptation strategies to address the impacts of climate change, aiming for a low-carbon, climate-resilient economy by 2030 (UNFCCC, 2015a).\n\nMoreover, Ethiopia’s investment in wind and geothermal energy, such as the Ashegoda Wind Farm and the Aluto Langano Geothermal Project, contributes to emission reductions by replacing fossil fuel-based power generation. These renewable projects are aligned with Ethiopia’s commitment to the Paris Agreement targets and its Nationally Determined Contributions (NDCs), which aim to reduce GHG emissions by 64% from business-as-usual levels by 2030 (UNFCCC, 2015b).\n\nEnergy security\n\nEthiopia’s focus on renewable energy has improved its energy security, reducing dependence on imported fossil fuels. The expansion of hydropower capacity, particularly with the GERD, positions Ethiopia as a regional leader in clean energy. The dam has the potential to generate over 6,450 megawatts (MW) of electricity, making Ethiopia one of the largest energy producers in Africa (African Development Bank, 2020). This enhanced energy generation capacity not only meets domestic demand but also allows Ethiopia to export electricity to neighboring countries, such as Sudan and Djibouti, which strengthens regional energy security (IRENA, 2020).\n\nHowever, the over-reliance on hydropower also poses risks due to climate variability, particularly droughts, which can affect water availability and, subsequently, energy production. Ethiopia is working to diversify its renewable energy mix by developing wind, solar, and geothermal projects to reduce this vulnerability and ensure a stable energy supply (USAID, 2021). Additionally, grid expansion and rural electrification efforts are improving energy access, contributing to long-term energy security by connecting more of the population to clean energy sources.\n\nJob creation\n\nThe shift towards renewable energy in Ethiopia has created new economic opportunities, particularly in job creation. The construction of the GERD alone employed over 12,000 workers during its peak, providing both direct and indirect jobs in the energy sector (World Bank, 2022). Furthermore, renewable energy projects, such as wind and solar farms, generate employment opportunities in construction, maintenance, and operation. For instance, the Ashegoda Wind Farm created several hundred jobs during its construction phase, and ongoing operations continue to require a skilled workforce (IRENA, 2021).\n\nAdditionally, Ethiopia’s efforts in rural electrification, particularly through off-grid solar solutions, have fostered small-scale employment opportunities in remote areas. Solar companies, often in collaboration with international partners, are training local technicians and entrepreneurs to install, maintain, and distribute solar systems, contributing to economic growth in underserved regions (USAID, 2021). As Ethiopia continues to scale its renewable energy sector, the potential for job creation is expected to rise, with projections of tens of thousands of new jobs across the green economy by 2030 (World Bank, 2022).\n\nTechnological challenges\n\nEthiopia faces significant challenges in terms of local expertise and infrastructure to fully harness advanced renewable energy technologies, such as wind and geothermal. The limited availability of technical skills for the installation, operation, and maintenance of energy systems has slowed the deployment of renewable energy projects (Mulugetta et al., 2021). Moreover, the technological gap in energy storage and grid integration is a major bottleneck in utilizing intermittent renewable sources like solar and wind (Tiruye et al., 2021).\n\nThe country’s energy infrastructure, especially in terms of grid expansion and integration, is underdeveloped. This restricts the capacity to connect rural areas to the national grid and integrate new renewable energy projects efficiently (Tesfay et al., 2024). The aging infrastructure also leads to frequent power outages, reducing the reliability of energy services (Fentahun, 2022).\n\nFinancial challenges\n\nThe countries to submit and update Nationally Determined Contributions (NDCs) and to enhance financial support for climate action in developing countries (UNFCCC, 2015b). Despite the Ethiopian government’s commitment to renewable energy, the financing needed for large-scale projects remains a significant hurdle. Many renewable energy initiatives require high upfront capital costs, which are difficult to meet due to limited domestic financial resources and underdeveloped financial markets (Benti, Mekonnen, et al., 2023a). International financing is also constrained by high-risk perceptions of investing in Ethiopia, especially related to political instability and bureaucratic delays (Teferra, 2022).\n\nAlthough Ethiopia is eligible for various global climate funds, the actual access to these resources remains limited due to insufficient institutional capacity to meet the stringent reporting and monitoring requirements associated with international climate finance (Kassaye & Bekele, 2021). Inadequate national coordination and project documentation often hinder Ethiopia from effectively mobilizing funds from mechanisms like the Green Climate Fund (Bhandary, 2024).\n\nInstitutional challenges\n\nInstitutional challenges in Ethiopia’s energy sector are largely related to weak governance and coordination among key stakeholders. Regulatory bodies often lack the technical expertise and resources needed to effectively implement and monitor renewable energy policies (Mengistu et al., 2020). Furthermore, there is a lack of coordination between various ministries and agencies, resulting in fragmented policy implementation (Admasu, 2020). While Ethiopia has introduced policies like the Climate Resilient Green Economy (CRGE) strategy and the National Electrification Program (NEP), enforcement and implementation remain inconsistent. Bureaucratic inefficiencies and delays in the approval of energy projects, as well as inconsistencies in tariff setting and power purchase agreements, have created an unstable environment for investors (Ayele, 2021). This is compounded by regulatory uncertainties in land use, which delay renewable energy project development (Demissie, 2021). High initial costs and infrastructure needs, while emphasizing the prospects for geothermal energy as a key source of sustainable power in Ethiopia (Kebede, 2021).\n\nPolicy implications in Ethiopia’s energy sector\n\nEthiopia’s policy framework has played a significant role in shaping its energy transition, with several ambitious strategies focused on reducing greenhouse gas (GHG) emissions and increasing renewable energy production. The Climate Resilient Green Economy (CRGE) Strategy, launched in 2011, remains the cornerstone of Ethiopia’s climate mitigation policy. The CRGE envisions a carbon-neutral economy by 2030, with the energy sector contributing significantly through renewable energy investments and energy efficiency programs (FDRE, 2011). The success of this strategy has been evident in Ethiopia’s increased hydropower capacity, which now accounts for over 90% of its electricity generation (Guta & Börner, 2017). However, despite the progress, several gaps exist in the implementation of these policies. One challenge is the limited integration of renewable energy sources beyond hydropower, such as wind and solar energy, which are crucial for diversifying Ethiopia’s energy mix. The National Electrification Program (NEP) 2.0, updated in 2019, aims to address this by promoting off-grid solar solutions, particularly for rural electrification, but its implementation has been hindered by financing and infrastructure constraints (World Bank, 2022).\n\nMoreover, while Ethiopia has made strides in policy formulation, institutional capacity and coordination remain key obstacles. The fragmented governance structures across different ministries and agencies often lead to inefficiencies in policy implementation. The Ministry of Water, Irrigation, and Energy (MoWIE), which oversees energy policies, frequently encounters challenges in aligning its actions with those of the Environmental Protection Authority (EPA) and regional governments (Teklu, 2018). Enhancing inter-ministerial coordination is critical to ensure the successful implementation of energy sector mitigation strategies.\n\nFurthermore, financial constraints continue to hamper Ethiopia’s ability to scale up its renewable energy projects. While the Green Climate Fund (GCF) and other international financial institutions have pledged support, domestic investment in renewable energy remains low. According to a study by (Benti, Mekonnen, et al., 2023a), Ethiopia’s renewable energy financing gap stands at several billion dollars, limiting the pace at which the country can achieve its CRGE targets. To bridge this gap, Ethiopia must attract more private-sector investments and strengthen public-private partnerships (PPPs) to finance large-scale renewable projects.\n\nFuture opportunities for scaling mitigation approaches in Ethiopia’s energy sector\n\nEthiopia has made significant strides in renewable energy, particularly in hydropower, which accounts for over 90% of the country’s electricity generation (Hailu and Kumsa, 2021). However, there is untapped potential in solar and wind energy. Studies suggest that Ethiopia has high solar irradiance and wind speeds, particularly in the Rift Valley region, which could be harnessed to diversify its energy mix and enhance energy security (Gebreslassie et al., 2024). Future opportunities lie in scaling up investment in these renewable sources, potentially through public-private partnerships.\n\nEthiopia’s geothermal potential, particularly in the Ethiopian Rift Valley, remains largely underdeveloped. The Aluto-Langano geothermal field has demonstrated success, but scaling geothermal energy projects can provide a steady and reliable renewable energy source, reducing reliance on hydropower, which is vulnerable to climate variability (Tesfaye et al., 2020). Further exploration and investment in geothermal power plants could contribute to Ethiopia’s energy mix and bolster resilience to climate change.\n\nOne of the most cost-effective mitigation strategies is improving energy efficiency in industrial, residential, and transportation sectors. According to a study by (Wondie et al., 2024), energy losses during transmission and distribution, as well as inefficient energy use in industries, contribute significantly to GHG emissions in Ethiopia. There is an opportunity to adopt energy-efficient technologies and implement policies that incentivize industries and households to reduce energy consumption.\n\nAlthough Ethiopia has made progress in developing policies such as the Climate Resilient Green Economy (CRGE) strategy, there are gaps in implementation and enforcement (Yalew, 2022). Future opportunities lie in strengthening the regulatory framework, improving institutional coordination, and ensuring robust monitoring and evaluation mechanisms. Streamlining climate and energy policies to align with national development goals can enhance the effectiveness of mitigation measures.\n\nEthiopia can capitalize on international climate financing mechanisms, such as the Green Climate Fund (GCF), to fund large-scale renewable energy projects and grid expansion (Mulatu, A. B., et al., 2023). Additionally, technology transfer from developed countries could accelerate the adoption of clean energy technologies. Future opportunities lie in creating favorable conditions for foreign direct investment (FDI) and enhancing collaborations with international organizations to secure the financial and technological resources needed to scale successful mitigation approaches.\n\n\nDiscussion\n\nEthiopia has made considerable progress in developing renewable energy projects, particularly through large hydropower dams like the Grand Ethiopian Renaissance Dam (GERD). However, the over-reliance on hydropower presents a significant vulnerability, as climate variability, such as droughts, can drastically reduce water availability and affect energy production. This reliance has also slowed the diversification into other renewable energy sources like wind, solar, and geothermal, which face additional technical, financial, and institutional barriers. Investment in non-hydropower renewables remains low, partly due to insufficient technological expertise and limited financial resources.\n\nEthiopia’s push towards energy efficiency has the potential to significantly reduce energy waste, especially in industrial and residential sectors. Nonetheless, the adoption of energy-efficient technologies is limited by high upfront costs and a lack of public awareness, particularly in rural areas. Furthermore, the country faces challenges in implementing energy audits and monitoring systems due to a shortage of skilled professionals. This limits the scale and impact of energy efficiency initiatives, and their sustainability is also uncertain, as they rely heavily on international funding, which may not be consistent in the long term.\n\nEthiopia has introduced comprehensive policy frameworks such as the Climate Resilient Green Economy (CRGE) strategy and the National Electrification Program (NEP 2.0) to guide its energy transition. However, the implementation of these policies has been hampered by weak institutional capacities and financial constraints. The lack of strong enforcement mechanisms, combined with coordination challenges among different governmental bodies, limits the effectiveness of these policies. Political instability and external economic pressures further exacerbate these issues, posing additional hurdles to the long-term success of Ethiopia’s energy policies.\n\nEthiopia has committed to reducing greenhouse gas emissions by focusing on renewable energy sources like hydropower. However, the reliance on hydropower leaves the country vulnerable to climate-induced risks, such as droughts, which can undermine its emission reduction efforts. While geothermal and wind projects are being explored, their contribution to the overall energy mix is still minimal due to slow technological and financial progress. This delay in scaling alternative renewables limits Ethiopia’s ability to meet its ambitious emission reduction targets within the desired timeframe.\n\nEthiopia’s energy security has improved due to its increasing energy generation capacity, mainly through hydropower projects. However, the lack of diversification in the energy mix leaves the country exposed to climate risks like droughts that can significantly reduce hydropower output. Furthermore, the country’s underdeveloped grid infrastructure limits electricity access, particularly in rural areas, making energy security a challenge. Ethiopia’s plans to export energy to neighboring countries could also be affected by geopolitical tensions, further complicating the energy security outlook.\n\nThe expansion of renewable energy projects, such as the construction of the GERD, has created employment opportunities, particularly in the construction phase. However, these job opportunities are not uniformly distributed, with rural areas, where unemployment is high, receiving less benefit. Moreover, the long-term employment prospects in the renewable energy sector are limited by a lack of local technical expertise. This shortage hampers the development of sustainable job markets in the operation and maintenance of renewable energy infrastructure, restricting overall employment growth in the energy sector.\n\nEthiopia’s renewable energy sector faces several technological challenges, particularly regarding the implementation and maintenance of wind, geothermal, and solar energy systems. The country lacks the necessary technical capacity for large-scale deployment of these technologies, and the grid infrastructure is not yet developed enough to integrate intermittent renewable energy sources like wind and solar efficiently. Additionally, the lack of energy storage technologies hinders the management of variable energy generation, further limiting the scalability of renewable energy projects.\n\nOne of the major barriers to scaling up renewable energy in Ethiopia is the limited availability of domestic financing. While Ethiopia is eligible for international climate finance, bureaucratic inefficiencies and a lack of institutional capacity slow access to these funds. Additionally, the perceived investment risks, coupled with political instability, deter private-sector investments in the energy sector. Without increased and consistent financial support, the expansion of renewable energy projects and the associated infrastructure will continue to face delays.\n\nInstitutional challenges play a critical role in the slow progress of Ethiopia’s renewable energy development. Weak coordination among government agencies, as well as inconsistent policies around land use, tariffs, and power purchase agreements, create uncertainties for investors. Furthermore, the lack of technical expertise within regulatory bodies limits the enforcement of energy policies and hinders the effective monitoring of ongoing projects. These governance issues, coupled with bureaucratic delays, impede the timely implementation of energy projects, limiting Ethiopia’s ability to achieve its energy targets.\n\nEthiopia’s potential to scale its renewable energy projects, particularly in solar, wind, and geothermal energy, presents significant opportunities for further reducing emissions and enhancing energy security. However, financial and technological limitations continue to be major barriers. The country’s reliance on international investment and funding makes it vulnerable to economic and political changes on a global scale. Additionally, the lack of adequate grid infrastructure and energy storage solutions poses a challenge to integrating renewable energy at scale, slowing the realization of Ethiopia’s long-term energy goals.\n\n\nConclusion and recommendation\n\nEthiopia’s commitment to renewable energy, particularly through hydropower, positions the country as a leader in clean energy generation in Africa. Significant projects like the Grand Ethiopian Renaissance Dam (GERD) illustrate the nation’s potential to enhance energy access and reduce greenhouse gas emissions. However, despite the progress made, challenges such as over-reliance on hydropower, underutilization of geothermal and wind resources, and obstacles in energy efficiency initiatives remain critical barriers to achieving energy security and sustainability. Effective implementation of policy frameworks, including the Climate Resilient Green Economy (CRGE) strategy and the National Electrification Program 2.0 (NEP 2.0), is essential for overcoming these challenges.\n\nTo realize its ambitious goals, Ethiopia must address the gaps in its energy sector through diversification, improved institutional coordination, enhanced financial access, capacity building, and robust policy evaluation mechanisms. As the nation strives toward a carbon-neutral economy by 2030, it is imperative to leverage its vast renewable energy resources while ensuring equitable energy access for all citizens.\n\n1. Increase investments in solar, wind, and geothermal energy to reduce dependence on hydropower. Policymakers should provide greater incentives, such as tax breaks or subsidies, to attract private investments into these sectors. 2. Establish a dedicated inter-agency task force to streamline policy implementation across different sectors, ensuring alignment of energy goals with environmental, economic, and social policies. 3. Explore innovative financing mechanisms like green bonds and blended finance to mobilize funds for renewable energy projects. Creating a conducive environment for private investment, including clear regulatory frameworks and guarantees, is crucial. 4. Focus on human capital development and technical capacity in the energy sector by expanding training programs for renewable energy professionals and promoting partnerships with international organizations. 5. Develop a robust monitoring and evaluation framework for energy sector policies to track progress towards mitigation goals. Regular assessments should guide adjustments to strategies based on performance metrics.\n\nThe author affirm that the study titled “Systematic Review of Mitigation Approaches in Ethiopia’s Energy Sector: Strategies for Sustainable Development and Climate Resilience\" complies with ethical standards. The review relied solely on publicly available data from peer-reviewed sources, with no direct involvement of human or animal subjects. No conflicts of interest exist, and all funding sources, if applicable, are disclosed.\n\nNot relevant.\n\n\nConsent for publication\n\nThe author approve to publish the manuscript.\n\n\nAuthor contribution\n\nWriting, formal analysis, investigation, presentation, interpretation, conceptualization, visualization, supervision methodology, validation and review: T.R. I author have read and agreed to the published version of the manuscript.\n\n\nDeclaration\n\nThe author, declare that the manuscript titled “Systematic Review of Mitigation Approaches in Ethiopia’s Energy Sector: Strategies for Sustainable Development and Climate Resilience” is original, has not been previously published, and is not under consideration elsewhere. There are no conflicts of interest, and all funding sources have been disclosed.",
"appendix": "Data availability\n\nA comprehensive literature search was systematically conducted across multiple databases, including Google Scholar, Scopus, Web of Science, and JSTOR, to identify peer-reviewed articles, government reports, and key grey literature.\n\nOpen Science Framework (OSF): Systematic Review of Mitigation Approaches in Ethiopia’s Energy Sector: Strategies for Sustainable Development and Climate Resilience https://doi.org/10.17605/OSF.IO/6SNQT (Indris, 2024).\n\nThis project contains the following underlying data:\n\n• TR reference infromation.pdf (https://osf.io/9h37u)\n\nData are available under the terms of the Creative Commons Zero (CC0 1.0 Universal).\n\nThis dataset is freely available for unrestricted access and use, as outlined in the license terms.\n\nReporting guidelines\n\nOpen Science Framework (OSF): PRISMA checklist and flow chart for “Systematic Review of Mitigation Approaches in Ethiopia’s Energy Sector: Strategies for Sustainable Development and Climate Resilience” https://doi.org/10.17605/OSF.IO/6SNQT (Indris, 2024).\n\nData are available under the terms of the Creative Commons Zero (CC0 1.0 Universal).\n\n\nReferences\n\nAdmasu Y: Governance and Coordination Challenges in Ethiopia’s Energy Sector. Journal of Energy Governance. 2020; 24(3): 123–135. Publisher Full Text\n\nBenti NE, Woldegiyorgis TA, Geffe CA, et al.: Overview of geothermal resources utilization in Ethiopia: Potentials, opportunities, and challenges. Scientific African. 2023b; 19: e01562. Publisher Full Text\n\nAfDB: East Africa Regional Energy Outlook. African Development Bank; 2020. Reference Source\n\nAndrews-Speed P, Zhang S: Energy Sector Reforms and Climate Change Mitigation. Energy Policy. 2019; 129: 597–605. Publisher Full Text\n\nAfrican Development Bank: East Africa Regional Energy Outlook. African Development Bank; 2020. Reference Source\n\nBenti NE, Mekonnen YS, Asfaw AA: Combining green energy technologies to electrify rural community of Wollega, Western Ethiopia. Scientific African. 2023a; 19: e01467. Publisher Full Text\n\nBhandary RR: The role of institutional design in mobilizing climate finance: Empirical evidence from Bangladesh, Brazil, Ethiopia, and Indonesia. PLOS Clim. 2024; 3(3): e0000246. Publisher Full Text\n\nDemissie B: Land Use Regulations and their Impact on Renewable Energy Projects in Ethiopia. Energy and Environment Journal. 2021; 32(2): 188–202. Publisher Full Text\n\nEthiopian Ministry of Water, Irrigation, and Energy: National Energy Efficiency Program. Ministry of Water, Irrigation, and Energy.2019.\n\nFederal Democratic Republic of Ethiopia: Climate Resilient Green Economy Strategy. Ministry of Environment and Forest; 2011. Reference Source\n\nFentahun Y: Chronic Energy Deficiency and Associated Factors Among Disabled Adults in Bahir Dar City, North West Ethiopia, 2021 (Doctoral dissertation).2022. Reference Source\n\nGebreslassie MG, Bekele G, Bahta ST, et al.: Developing community energy systems to facilitate Ethiopia’s transition to sustainable energy. Energy Research & Social Science. 2024; 117: 103713. Publisher Full Text\n\nGebru S: Wind Energy Potential in Ethiopia: Prospects and Challenges. Journal of Renewable Energy and Sustainable Development. 2020; 8(3): 15–23. Publisher Full Text\n\nGebrehiwot K: Financing Renewable Energy Development in Ethiopia: Challenges and Opportunities. Renewable Energy Journal. 2020; 41(3): 188–200. Publisher Full Text\n\nGIZ: Energy Efficiency for Industrial Applications in Ethiopia. German International Cooperation; 2020. Reference Source\n\nGlobal Alliance for Clean Cookstoves: 2019. Reference Source\n\nGuta D, Börner J: Energy security, uncertainty and energy resource use options in Ethiopia: A sector modelling approach. International Journal of Energy Sector Management. 2017; 11(1): 91–117. Publisher Full Text\n\nHailemariam H: Renewable Energy in Ethiopia: Potentials, Status and Challenges. Journal of Renewable Energy. 2020; 18(1): 35–45. Publisher Full Text\n\nHailu AD, Kumsa DK: Ethiopia renewable energy potentials and current state. Aims Energy. 2021; 9(1): 1–14. Publisher Full Text\n\nHoffmann H, Uckert G, Reif C, et al.: Traditional biomass energy consumption and the potential introduction of firewood efficient stoves: insights from western Tanzania. Regional Environmental Change. 2015; 15: 1191–1201. Publisher Full Text\n\nIPCC: Sixth Assessment Report: Impacts, Adaptation, and Vulnerability. Intergovernmental Panel on Climate Change; 2022. Reference Source\n\nIEA: Global Energy Review: CO2 Emissions in 2021. International Energy Agency; 2021. Reference Source\n\nIRENA: Renewable Energy in Africa: Key Drivers and Policies. International Renewable Energy Agency; 2020. Reference Source\n\nIRENA: Renewable Energy Market Analysis: Africa and Its Regions. International Renewable Energy Agency; 2021. Reference Source\n\nIndris TR: Systematic Review of Mitigation Approaches in Ethiopia’s Energy Sector: Strategies for Sustainable Development and Climate Resilience.2024. Publisher Full Text\n\nKarekezi S, Kithyoma W: Sustainable Energy in Africa: Challenges and Prospects. Energy Policy. 2021; 127: 189–199. Publisher Full Text\n\nKassaye A, Bekele M: Institutional Barriers to Accessing Global Climate Finance in Ethiopia. Climate Policy and Governance Journal. 2021; 15(2): 145–156. Reference Source\n\nKammen DM, Kirubi C: Renewable Energy for Rural Electrification in Sub-Saharan Africa. Renewable and Sustainable Energy Reviews. 2021; 11(5): 1057–1073. Publisher Full Text\n\nKebede Y: Geothermal Energy Development in Ethiopia: Progress and Prospects. Geothermal Energy Journal. 2021; 14(1): 78–92. Publisher Full Text\n\nKarimi A, Sanaieian H, Farhadi H, et al.: Evaluation of the thermal indices and thermal comfort improvement by different vegetation species and materials in a medium-sized urban park. Energy Reports. 2020; 6: 1670–1684. Publisher Full Text\n\nLahnaoui A, Venghaus S, Kuckshinrichs W: Assessing the drivers of energy supply and demand in Sub-Saharan Africa. Energy Strategy Reviews. 2024; 54: 101483. Publisher Full Text\n\nLo K, Broto VC: Co-benefits, contradictions, and multi-level governance of low-carbon experimentation: Leveraging solar energy for sustainable development in China. Global Environmental Change. 2019; 59: 101993. Publisher Full Text\n\nMengistu T, et al.: Institutional Barriers to Renewable Energy Development in Ethiopia. Energy Policy. 2020; 140: 111425. Publisher Full Text\n\nMondal MAH, Bryan E, Ringler C, et al.: Ethiopian energy status and demand scenarios: prospects to improve energy efficiency and mitigate GHG emissions. Energy. 2018; 149: 161–172. Publisher Full Text\n\nMulugetta Y, et al.: Renewable Energy Technology Transfer to Ethiopia: Barriers and Opportunities. Energy for Sustainable Development. 2021; 59: 20–31. Publisher Full Text\n\nNegash T, Aklilu A, Tesfaye M: Leveraging International Climate Finance for Ethiopia’s Renewable Energy Sector. Renewable Energy. 2021; 174: 1238–1249. Publisher Full Text\n\nOndraczek J: Are Countries with Geothermal Resources Shifting to Renewable Energy? Evidence from Kenya and East Africa. Renewable Energy. 2021; 92: 528–539. Publisher Full Text\n\nSilitonga AS, Shamsuddin AH, Mahlia TMI, et al.: Biodiesel synthesis from Ceiba pentandra oil by microwave irradiation-assisted transesterification: ELM modeling and optimization. Renewable Energy. 2020; 146: 1278–1291. Publisher Full Text\n\nSNV: Improved Cookstoves in Ethiopia. SNV Netherlands Development Organization; 2021. Reference Source\n\nTakase M, Kipkoech R, Essandoh PK: A comprehensive review of energy scenario and sustainable energy in Kenya. Fuel Communications. 2021; 7: 100015. Publisher Full Text\n\nTeferra BT: Designing and planning of Ethiopia’s biomass-to-biofuel (bioethanol and biodiesel) supply chain through integrated strategic-tactical optimization model under economic and environmental dimensions.2022.\n\nTesfay AH, Gebreslassie MG, Lia L: Sustainability challenges of hydropower and its implication on Ethiopia’s economy. International Journal of Sustainable Engineering. 2024; 17(1): 1–14. Publisher Full Text\n\nTeklu TW: Should Ethiopia and least developed countries exit from the Paris climate accord?–Geopolitical, development, and energy policy perspectives. Energy Policy. 2018; 120: 402–417. Publisher Full Text\n\nTiruye GA, Besha AT, Mekonnen YS, et al.: Opportunities and challenges of renewable energy production in Ethiopia. Sustainability. 2021; 13(18): 10381. Publisher Full Text\n\nUNFCCC: Ethiopia’s Nationally Determined Contributions (NDCs). United Nations Framework Convention on Climate Change; 2015a. Reference Source\n\nUNFCCC: Paris Agreement. United Nations Framework Convention on Climate Change; 2015b. Reference Source\n\nUSAID: Ethiopia Power Africa Fact Sheet. United States Agency for International Development; 2021. Reference Source\n\nWondie M, Teshale B, Assabu G, et al.: Renewable energy potential assessment and modeling for improving electric energy accessibility in rural areas of northwest Ethiopia. Arabian Journal of Geosciences. 2024; 17: 222. Publisher Full Text\n\nWorld Bank: Ethiopia’s National Electrification Program (NEP).2022. Reference Source\n\nWorld Resources Institute: 2020. Reference Source\n\nYalew AW: The Ethiopian energy sector and its implications for the SDGs and modeling. Renewable and Sustainable Energy Transition. 2022; 2: 100018. Publisher Full Text"
}
|
[
{
"id": "342567",
"date": "13 Dec 2024",
"name": "Abdul-Wahab Tahiru",
"expertise": [
"Reviewer Expertise n/a"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReviewer Comments Introduction\nClarity and Organization:\nThe introduction presents a comprehensive overview of the global and regional energy sector challenges, with a particular focus on Ethiopia. However, the organization could be improved to enhance readability and flow. For instance, the transition from global to regional to country-specific discussions feels abrupt in some sections. There is some repetition in discussing renewable energy potential and challenges across Africa and Ethiopia, which could be streamlined for conciseness.\n\nContextual Relevance:\nThe introduction successfully establishes the global significance of GHG emissions from the energy sector and contextualizes it within Africa and Ethiopia. However, some statements, particularly those discussing specific countries like Kenya and South Africa, could be better connected to the manuscript's focus on Ethiopia.\n\nTerminology and Consistency:\nEnsure consistent terminology throughout the introduction. For instance, terms like \"low-carbon technologies,\" \"clean energy,\" and \"renewable energy\" are used interchangeably but could benefit from clear definitions to avoid ambiguity. The phrase \"focusing on challenges like limited access, financial constraints, and policy gaps\" (Africa's context) lacks a verb, making it grammatically incomplete.\n\nSources and Citations:\nThe manuscript demonstrates strong referencing, citing key sources. However, some references (e.g., \"From global climate initiatives to accelerate the development of renewable energy projects, highlighting key challenges and opportunities for attracting investments\") lack clarity and might need rephrasing for coherence. Ensure all sources cited (e.g., \"Federal Democratic Republic of Ethiopia, 2011\") are current and accurately referenced in the bibliography.\n\nCountry-Specific Focus:\nThe manuscript transitions into Ethiopia-specific challenges effectively in later paragraphs. However, the country-specific discussion could begin earlier in the introduction to maintain thematic focus. The discussion on Ethiopia’s Climate Resilient Green Economy (CRGE) strategy is well-placed but could briefly reference how these efforts align with regional trends or lessons learned from other countries.\n\nObjective Statement: The \"Main Objective\" and \"Specific Objectives\" sections are clearly defined and align with the introduction. However, it would be helpful to explicitly tie these objectives to the challenges and gaps identified in the introduction for a stronger narrative connection.\nMethodology Section\nClarity and Consistency:\nThe methodology section provides a thorough overview of the systematic review process; however, there are inconsistencies in verb tense usage (e.g., \"has follow,\" \"has involve\"). Consistency in past tense is essential throughout this section since the review appears to describe completed actions. The phraseology in some areas is unclear, such as \"interpret and discussed into a structured way,\" which requires rephrasing for clarity and grammatical accuracy.\n\nAdherence to PRISMA Guidelines:\nThe mention of PRISMA guidelines is commendable as it ensures a rigorous and transparent approach. However, it would be beneficial to explicitly reference key PRISMA elements, such as how the review addressed the risk of bias and study quality assessment.\n\nSearch Strategy and Inclusion Criteria:\nThe search strategy is well-defined, with specific databases and keywords listed. However, the justification for choosing databases like Google Scholar (which often includes non-peer-reviewed content) could be clarified. The inclusion and exclusion criteria are clear but could be strengthened by explaining how significant grey literature is identified and assessed for quality.\n\nData Extraction and Synthesis:\nThe use of a standardized data extraction form is a strong point. However, details on how the form was validated or how discrepancies were resolved between reviewers would improve transparency. The narrative synthesis approach is appropriate, but further explanation of how quantitative results were summarized and compared across studies would enhance replicability.\n\nFlowchart and Checklist:\nReferring to a systematic review flowchart and checklist is a good practice. However, it would be beneficial to briefly describe the key features of these tables in the text rather than solely relying on readers to consult them. For instance, mention specific quality assessment criteria included in the checklist.\n\nReproducibility and Rigor:\nWhile the methodology outlines a robust review process, additional details on quality assessment tools and techniques for mitigating bias during study selection and data extraction would strengthen the rigor of the review.\n\nGrammar and Syntax:\nPhrases like \"Titles and abstracts of studies has been reviewed\" and \"Eligible studies has been those\" contain grammatical errors. Consistently use \"were\" instead of \"has been\" to maintain proper past tense agreement.\n\nRecommendations for Improvement:\nVerb Tense Consistency: Use past tense consistently to reflect that the described methodology has already been implemented. PRISMA Details: Include more specific information on how PRISMA guidelines were applied, particularly in quality assessment and bias mitigation. Database Justification: Clarify why certain databases were chosen, especially those with potential non-peer-reviewed content, and how their inclusion impacts the review's validity. Quality Assessment: Provide more detail on how study quality was evaluated and how this influenced the inclusion of studies. Enhanced Flow and Grammar: Edit for grammatical accuracy and improve flow by avoiding repetitive phrases and awkward constructions. Describe Tables: Briefly describe the contents and significance of the flowchart and checklist within the text to provide context.\nResults The results section is comprehensive and demonstrates Ethiopia’s progress in renewable energy and climate mitigation. However, there is room for improvement in structure, clarity, and depth of analysis, particularly regarding challenges, policy implementation, and future opportunities. Incorporating these suggestions would enhance the rigor and accessibility of the findings. Discussion\nStreamline Content: Reduce redundancy by merging overlapping sections. For instance, combine paragraphs discussing hydropower vulnerabilities and diversification challenges into a cohesive analysis. Incorporate Data: Add relevant statistics and examples, such as Ethiopia's current energy mix, investment levels, or emission reduction targets, to enhance credibility. Expand on Solutions: Discuss specific strategies, such as international partnerships, technological transfers, or policy incentives, to overcome the identified barriers. Enhance Employment Insights: Provide more details on how Ethiopia can build local technical expertise and create long-term employment opportunities in renewable energy. Policy Implementation: Offer more insights into how Ethiopia can strengthen institutional coordination and enforcement mechanisms to effectively implement policy frameworks.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1377
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https://f1000research.com/articles/13-1376/v1
|
18 Nov 24
|
{
"type": "Research Article",
"title": "Evaluation of Knowledge and Perception of the Third Molar Extraction Procedure Among Patients in the Eastern Province, Saudi Arabia: A Cross-Sectional Study",
"authors": [
"Sami Alshehri",
"Turki Alshehri",
"Hadeel AlMutiri",
"Abdulla Aljami",
"Ahmed Alsubaie",
"Faisal E. Aljofi",
"Mishali AlSharief",
"Manal AlSaadoun",
"Yasser S. Alali",
"Yousif A. Al-Dulaijan",
"Sami Alshehri",
"Hadeel AlMutiri",
"Abdulla Aljami",
"Ahmed Alsubaie",
"Faisal E. Aljofi",
"Mishali AlSharief",
"Manal AlSaadoun",
"Yasser S. Alali",
"Yousif A. Al-Dulaijan"
],
"abstract": "Background Third molar extraction is one of the most common oral surgical procedures globally. This study assessed patients’ knowledge of third molar extraction procedures.\n\nMethods A self-administered questionnaire was administered to patients (N=384) of the dental hospital at Imam Abdulrahman bin Faisal University in the eastern province. The questionnaire covered demographic data, knowledge of third molar extraction, and patients’ perception questions. SPSS Version 24 was used for statistical analysis. Chi-square and Fisher’s Exact test were used. P-values less than or equal to 0.05 were considered statistically significant.\n\nResults According to the demographical characteristics of the patient who received 3rd molar removal surgery. As per the history of the extraction, 45% had previous 3rd molar extraction experience, whereas 55% had no previous dental surgical experience. There was no significant difference between the groups with the knowledge about the extraction (p-0.187). Patients with no previous history were more aware of the correct time for 3rd molar extraction at 27% vs 19%, respectively (P=0.046*). Patients with a previous history of third molar extraction showed significant results of knowledge in terms of taking medication prior to 3rd molar surgical procedure.\n\nConclusion The patient with previous experience with third molar extraction showed low misconceptions. However, further studies should consider increasing the knowledge and correcting the patients’ perceptions.",
"keywords": [
"Extraction",
"wisdom teeth",
"difficulty indices",
"postoperative pain",
"third molar"
],
"content": "Introduction\n\nThird molar extraction is one of the most frequently performed oral surgical procedures worldwide.1 Tooth impaction is defined as the inability of the tooth to erupt in a full functional position in the oral cavity.2 Clinical and radiographical evaluations could predict the degree of difficulty of third molar extraction preoperatively.3 The patient’s advanced age, depth, angulation of the impaction, and proximity to the inferior alveolar canal, maxillary sinus, and infratemporal fossa contribute to the extraction difficulty.4 Multiple theories elucidated the rationale behind third molar impactions: the discrepancy between the dental arch circumference and the sum of the mesiodistal width of the teeth, the attrition theory, and the discrepancy between dental and skeletal maturation.5\n\nThe eruption of third molars usually begins at the age of 17 to approximately 21 years.5 However, it is estimated that third molars fail to erupt in 25% of the population.6 Third molars are indicated for extraction if they include one or more of the following: developmental cysts, infections, recurrent episodes of pericoronitis, a periodontal disease affecting the adjacent teeth, interfering with adjacent teeth eruption, non-restorable or pulpal involvement, and for orthodontic or orthognathic considerations.7\n\nThere are some factors to be taken into consideration during decision-making for third molar extraction, such as the tooth position, proximity to vital structures, limited mouth opening, ankylosis, history of radiation therapy, medications such as a bisphosphonate, as well as overall patient health.8 In wisdom tooth extraction, According to Seymour et al., post-operative discomfort, pain, swelling, and bleeding are commonly associated with the procedure.9 A post-operative symptoms severity (PoSSe) scale was developed to measure the discomfort and severity of symptoms following third molar extraction, and it was shown that 97% of patients suffered from post-operative pain.10\n\nOperative factors have little bearing on patients’ quality of life (QOL).11 In aiming to improve the patient’s experience, multiple studies investigated the effect of medications on pain management studies). Monaco G. et al. concluded that antibiotic prophylaxis effectively prevented wound infection and postoperative pain in young patients after removing lower third molars.6 Another study reported that Cryotherapy effectively decreased postoperative swelling, pain, and limitation of mouth opening, improving patients’ QOL.12 An additional study showed a high association between patients’ anxiety and post-operative pain. Patient awareness of the procedure could minimize anxiety about wisdom teeth extraction.13 The author suggested conducting a separate consultation with an Oral and Maxillo-Facial Surgeon (OMFS) to make the procedure more comprehensible to the patient.\n\nOn the other hand, other studies reported that separate wisdom teeth consultation did not reduce the level of anxiety.14 However, adequate awareness about the procedure is required for all patients, especially anxious patients.15 It has been shown that patients with more inquiries are more anxious than others, and women are more anxious than men.16\n\nOverall, the true perception of patients about the preoperative, intraoperative, and postoperative nature of wisdom teeth extraction could positively impact their experience with wisdom teeth extraction.17 The clinician must know that all patients require sufficient information regarding the procedure. It’s essential to guide surgeons to optimize the surgical procedure, increase patient comfort, and decrease postoperative risks.18 Brasileiro B et al. assessed patients’ preoperative, intraoperative, and postoperative perception prior to third molar extraction. They found that 28.4% of respondents misunderstood the type of medications received preoperatively, some of the patients expressed concerns about the anesthesia technique and discomfort post-operatively, 23.9% and 17.9% respectively, and the most asked question was “Will all my teeth be removed at once?” in 59.6%.11 Comparing patients with previous extraction experience and those without experience, patients with no experience had more questions and misconceptions than the ones with prior experience.18\n\nDue to the gap of knowledge in the literature regarding the nature of third molar extractions in relation to knowledge and misconception, this cross-sectional observational study aimed to investigate patients’ knowledge and misconceptions about third molar extraction among patients visiting Imam Abdulrahman bin Faisal University Dental Hospital in the Eastern province of Saudi Arabia.\n\n\nMethods\n\nA cross-sectional observational study based on patients’ knowledge and perception regarding third molar extraction was conducted on patients seen at the Dental Hospital at Imam Abdulrahman bin Faisal University in the Eastern province of Saudi Arabia.\n\nA self-administered questionnaire has been distributed and collected from patients registered at the Dental Hospital of Imam Abdulrahman bin Faisal University who attended for treatment. Patients with mental illness, disability, inability to write and read, or individuals aged less than 18 years who a legal guardian did not accompany were excluded from this study.\n\nThe required sample size was calculated to be 384 patients based on the following assumptions: margin of error = 5%, confidence level = 95%, sample proportion = 50%, and z coefficient of 1.96.\n\nA self-administered validated questionnaire has been distributed and consists of two parts. The first part includes patients’ demographic information (age, gender, education level, history of third molar extraction). The second part is divided into two categories; the first is knowledge of third molar extraction, eruption, causes for extraction, mandatory of third molar extraction, multiple extractions at the same visit, anesthesia technique, dental phobia, and relationship between smoking and healing process. The second part is patients’ perception questions, which include anxiety relief during the surgical procedure, similarities in the extraction of the third molar to other molars, pre-operative and post-operative medications, and difficulty of third molar extraction teeth alignment after third molar extraction. The questionnaire was calibrated as a pilot study on 30 patients.\n\nData was initially recorded in Excel and then transferred to SPSS (Version 24, IBM, Armonk, NY) for further analysis. Where appropriate, descriptive statistics were calculated using frequency, percentages, mean, and standard deviations. The Chi-square/Fisher’s Exact test was used where appropriate for inferential statistics. Knowledge items were coded as 0=for misconception and 1=for correct answer. Multivariate logistic regression was used to evaluate the probable association with knowledge from patients with previous experience. P-values less than or equal to 0.05 were statistically significant.\n\n\nResults\n\nIn total, 409 patients had third molar extractions, of which 266 (65%) were male and 35% were female. Most patients were Saudi nationals (89%), and 46% were between 18 and 24 years old. Table 1 shows the demographic characteristics of the patients who had third molar removal surgery. As per history with the extraction, 45% had previous wisdom tooth extraction experience, whereas 55% had no previous dental surgical expertise.\n\nIn this study, the most common indication for wisdom teeth extraction was the abnormal path of tooth eruption (24%), followed by pain or decayed teeth (19%). Figure 1 summarizes all other indications of wisdom teeth extraction. Patients were divided into two groups: previous experience with the extraction and no previous extraction, and a comparison was done with knowledge items. Quantitatively, no significant difference was found between the groups with knowledge about the extraction (p-0.901). A qualitative comparison is presented in Table 2. Patients with no previous history were found to be more aware of the correct time for third molar eruption, 27%, vs. patients with a previous history of extraction, 19%, and the association was also statistically significant (p-0.046). Correct knowledge level about items, extraction of the third molar is mandatory (67% vs. 73%), a phobia about pain and actual pain feeling (54% vs. 51%), and smoking after the extraction delayed the healing process (49% vs 50%) was almost same between both groups without any statistical significance. Additionally, the misconception about anesthetic technique and extraction of more than 1 extraction was found to be highest in both groups with no statistically significant difference.\n\n* Significant at 0.05.\n\nTable 3 presents the patients’ perceptions with and without previous experience with extraction. Crowded teeth can be aligned by extraction; Group 2 (previous experience) was more confident than Group 1 (no experience) (42% vs. 37% respectively) but not significantly different. Regarding the medication before the surgery, group 2 was statistically higher with the right perception (47% vs. 25%) (p-0.001). Other perceptions were not statistically different between groups 1 and 2. Analgesics were the most common choice among the other medications mentioned (34%) for post-operative medicines Figure 2. The majority (43%) thought all mentioned medication should be taken after the surgery.\n\n* Significant at 0.05.\n\nMultiple logistic regression showed no statistically significant factors associated with the knowledge level Table 4. The chance of correct knowledge about the eruption time was 1.489 times higher among patients with previous experience. Similarly, those who have prior experience know better (OR = 1.230) about the pain and anxiety relationship during the surgery. For the rest of the items, the knowledge was not as expected from the experienced group.\n\n\nDiscussion\n\nThe present study aimed to investigate the knowledge and misconceptions of patients about third molar extraction. Out of 409 total responses, 65% of those who attended the dental hospital seeking different dental treatments were males. Compared to females, a study showed that males attended more dental clinics for third molar extraction.19 However, a study reported a higher female-to-male ratio regarding third molar extraction.20 This kind of discrepancy in demographic factors can be found in many studies. However, regarding the third molar extraction procedure, a systematic review study highlighted females presented with 14% more than males in terms of having at least one missing third molar.21 In our study, the age group between 18 and 24 years was predominant among the participants. Generally, this is the eruption time of third molars.22 A previous study showed that patients undergoing third molar extraction were noted in the age group of 21 to 30 years.23\n\nAbnormal eruption in the current study was the most common chosen factor, which indicated third molar extraction at 24%, followed by caries and pain at 19%. Additionally, a result revealed by a local study in Saudi Arabia which investigated the prevalence of impaction and the reasons for extraction found that the most common indication for extraction of the third molar was the asymptomatic and prophylactic reason (66.8%), and the symptomatic was (33.2%).24 In contrast to our findings, Dhafar et al. reported that the caries of third molars was the first indication(42.3%), followed by the eruption abnormalities and prophylactic reason (39.2%).25 This comes in agreement with another study by Adeyemo et al. on caries factor.26 However, many factors and reasons can lead to third molar extraction, as discussed previously by Steed MB et al.27\n\nOur findings compared the misconceptions of patients with and without a previous history of third molar extraction, which resulted in more correct answers from participants in the group with previous extraction history. This agrees with a previous study that evaluated the pre-operative perceptions of patients who underwent third molar extraction and found low misconception among groups with a previous history of third molar extraction.11\n\nPatients with and without a previous history of third molar extraction showed no significant difference in knowledge. Both groups presented high percentages of correct answers about the third molar age eruption. Moreover, it was mentioned in the previous study that eruption starts at 17 years old in the oral cavity28 regarding whether extraction of the third molar is mandatory; for this answer, as reported, the decision will be according to the presence of disease and if the tooth asymptomatic or not.29 Our study showed a misconception about whether it is doable to extract the four wisdoms simultaneously; this can be done locally or under general anesthesia according to the case difficulties. Many variables can be addressed to evaluate the case, either patient-related or third molar-related.3 Misconceptions regarding the anesthesia technique were noticed in the current study. Generally, the same technique can be used to extract other molars besides different techniques.30,31\n\nThere was no significant difference (p-0.325) between the groups when it came to relationship between feeling pain and anxiety/phobia. Additionally, anxiety was reported to be presented with more pain to the patient.32 However, another study evaluated separate consultation appointments prior to third molar extraction as it was effective according to the patients.33 Besides that, his relationship was also found in another study in which they reported a significant relationship between less post-operative pain and verbal information about the extraction steps.34 We believe different ways to reduce anxiety should be considered before third molar extraction. For example, a significant reduction in anxiety levels was reported after using the audiovisual method.35\n\nParticipants showed no statistical significance in both groups regarding whether smoking after extraction delayed the healing process (49% vs 50%). Such answers give us an overview of the lack of knowledge about this fact. In addition, oral hygiene should be maintained after oral surgery to avoid any source of infection and promote healing. Furthermore, a review study reported that tobacco can affect the surgical site after tooth extraction.36\n\nThe knowledge of patients about post-operative medications in our study illustrated that all three analgesics, antibiotics, and mouthwashes should be taken after the third molar extraction (43%); patients answered analgesics only (34%), followed by antibiotics (15%), then mouthwashes (8%). It was reported that analgesics are the most effective medications for pain relief after dental extraction.37 The role of the antibiotic in oral surgery to prevent post-operative infection was statistically significance.,38 but it is not required for simple extraction.39\n\nAs per our knowledge no previous study was conducted in Saudi Arabia similar to our study. However, some limitations can be addressed in our study, such as the fact that the participants were only from one dental hospital in the eastern province of Saudi Arabia, convenience sample, the study design and patients are not aware of their correct answers after filling out the survey. Thus, further investigation should be done to increase the patients’ knowledge and awareness regarding perioperative and postoperative third molar extraction. We recommend further research to evaluate the pre- and post-knowledge scores and use educational material to assess the improvement level.\n\n\nConclusions\n\nPatients with previous experience presented greater confidence regarding third molar extraction, although this difference was not statistically significant. Additionally, patients with previous experience demonstrated a better understanding of pain and anxiety relationship during the surgery which may assist the surgeon in determining the need for sedation prior to surgery\n\n\nEthics and consent\n\nThe study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Imam Abdulrahman Bin Faisal University (IRB-2022-02-397) (approval date: 20th of October, 2022). Written informed consent was obtained from all participants included in the current study.",
"appendix": "Data availability statement\n\nFigshare. Evaluation of knowledge and perception of the third molar extraction procedure among patients in the eastern province, Saudi Arabia: A cross-sectional study https://doi.org/10.6084/m9.figshare.27303840.40\n\nThis project contains the following underlying data:\n\n• Third molar extraction data sheet 3.xlsx. Data for patients participated to fill questionnaire that evaluate the knowledge and perceptions regarding third molar extraction.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare. Questionnaire regarding knowledge of third molar extraction, https://doi.org/10.6084/m9.figshare.27614073.41\n\nThis project contains the following extended data:\n\n• Questionnaire regarding knowledge of third molar extraction.docx. Questionnaire consist of 2 parts, first part: questions regarding the demographic data and previous history of third molar extraction, second part: questions about the knowledge of participants regarding third molar extraction.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAli A, Benton J, Yates J: Risk of inferior alveolar nerve injury with coronectomy vs surgical extraction of mandibular third molars—a comparison of two techniques and review of the literature. J. Oral Rehabil. 2018; 45: 250–257. PubMed Abstract | Publisher Full Text\n\nJanakiraman EN, Alexander M, Sanjay P: Prospective analysis of frequency and contributing factors of nerve injuries following third-molar surgery. J. Craniofac. Surg. 2010; 21: 784–786. PubMed Abstract | Publisher Full Text\n\nGay-Escoda C, Sánchez-Torres A, Borrás-Ferreres J, et al.: Third molar surgical difficulty scales: systematic review and preoperative assessment form. Med. Oral Patol. Oral Cir. Bucal. 2022; 27: e68–e76. Publisher Full Text\n\nSánchez-Torres A, Soler-Capdevila J, Ustrell-Barral M, et al.: Patient, radiological, and operative factors associated with surgical difficulty in the extraction of third molars: a systematic review. Int. J. Oral Maxillofac. Surg. 2020; 49: 655–665. PubMed Abstract | Publisher Full Text\n\nDe Bruyn L, Vranckx M, Jacobs R, et al.: A retrospective cohort study on reasons to retain third molars. Int. J. Oral Maxillofac. Surg. 2020; 49: 816–821. PubMed Abstract | Publisher Full Text\n\nMonaco G, Tavernese L, Agostini R, et al.: Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients. J. Oral Maxillofac. Surg. 2009; 67: 1467–1472. PubMed Abstract | Publisher Full Text\n\nFragiskos F: Surgical extraction of impacted teeth. Oral Surg. 2007; 121–179. Springer. Publisher Full Text\n\nHaug RH, Abdul-Majid J, Blakey GH, et al.: Evidence-based decision making: the third molar. Dent. Clin. N. Am. 2009; 53: 77–96. PubMed Abstract | Publisher Full Text\n\nSeymour R, Meechan J, Blair G: An investigation into post-operative pain after third molar surgery under local analgesia. Br. J. Oral Maxillofac. Surg. 1985; 23: 410–418. PubMed Abstract | Publisher Full Text\n\nRuta D, Bissias E, Ogston S, et al.: Assessing health outcomes after extraction of third molars: the postoperative symptom severity (PoSSe) scale. Br. J. Oral Maxillofac. Surg. 2000; 38: 480–487. PubMed Abstract | Publisher Full Text\n\nBrasileiro BF, de Bragança RMF , Van Sickels JE: An evaluation of patients’ knowledge about perioperative information for third molar removal. J. Oral Maxillofac. Surg. 2012; 70: 12–18. PubMed Abstract | Publisher Full Text\n\nWhite RP Jr, Shugars DA, Shafer DM, et al.: Recovery after third molar surgery: clinical and health-related quality of life outcomes. J. Oral Maxillofac. Surg. 2003; 61: 535–544. PubMed Abstract | Publisher Full Text\n\nIdris AM, Al-Mashraqi AA, Abidi NH, et al.: Third molar impaction in the Jazan region: evaluation of the prevalence and clinical presentation. Saudi Dent J. 2021; 33: 194–200. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan Wijk A , Lindeboom J: The effect of a separate consultation on anxiety levels before third molar surgery. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2008; 105: 303–307. PubMed Abstract | Publisher Full Text\n\nEnkling N, Marwinski G, Jöhren P: Dental anxiety in a representative sample of residents of a large German city. Clin. Oral Investig. 2006; 10: 84–91. PubMed Abstract | Publisher Full Text\n\nGarip H, Abalı O, Göker K, et al.: Anxiety and extraction of third molars in Turkish patients. Br. J. Oral Maxillofac. Surg. 2004; 42: 551–554. PubMed Abstract | Publisher Full Text\n\nKolte V, Shenoi R, Ghodeswar S, et al.: Effectiveness of patients’ knowledge about perioperative information prior to third molar removal. IJDR. 2014; 3: 1–4. Publisher Full Text\n\nGrossi GB, Maiorana C, Garramone RA, et al.: Assessing postoperative discomfort after third molar surgery: a prospective study. J. Oral Maxillofac. Surg. 2007; 65: 901–917. Publisher Full Text\n\nMurthi M, Dhasarathan P, Rajendran D: Retrospective study of the prevalence of dry socket in patients with mandibular third molar extraction. World. 2020; 11: 426.\n\nDereci O, Saruhan N, Tekin G: The comparison of dental anxiety between patients treated with impacted third molar surgery and conventional dental extraction. Biomed. Res. Int. 2021; 2021: 7492852.\n\nCarter K, Worthington S: Morphologic and demographic predictors of third molar agenesis: a systematic review and meta-analysis. J. Dent. Res. 2015; 94: 886–894. PubMed Abstract | Publisher Full Text\n\nAhlqwist M, Gröndahl HG: Prevalence of impacted teeth and associated pathology in middle-aged and older Swedish women. Community Dent. Oral Epidemiol. 1991; 19: 116–119. PubMed Abstract | Publisher Full Text\n\nRizqiawan A, Lesmaya YD, Rasyida AZ, et al.: Postoperative complications of impacted mandibular third molar extraction related to patient’s age and surgical difficulty level: a cross-sectional retrospective study. Int. J. Dent. 2022; 2022: 1–6. Publisher Full Text\n\nAlfadil L, Almajed E: Prevalence of impacted third molars and the reason for extraction in Saudi Arabia. Saudi Dent J. 2020; 32: 262–268. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDhafar W, Mandura R, Dafar A, et al.: Reasons for third molars extraction by different healthcare providers. Int. J. Pharm. Res. Allied Sci. 2020; 9: 189–194.\n\nAdeyemo WL, James O, Ogunlewe MO, et al.: Indications for extraction of third molars: a review of 1763 cases. Niger. Postgrad. Med. J. 2008; 15: 42–46. PubMed Abstract | Publisher Full Text\n\nSteed MB: The indications for third-molar extractions. J. Am. Dent. Assoc. 2014; 145: 570–573. Publisher Full Text\n\nTimme M, Viktorov J, Steffens L, et al.: Third molar eruption in orthopantomograms as a feature for forensic age assessment—a comparison study of different classification systems. Int. J. Legal Med. 2023; 137: 765–772. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKandasamy S, Rinchuse DJ, Rinchuse DJ: The wisdom behind third molar extractions. Aust. Dent. J. 2009; 54: 284–292. PubMed Abstract | Publisher Full Text\n\nTsukimoto S, Takasugi Y, Aoki R, et al.: Inferior alveolar nerve block using the anterior technique to anesthetize buccal nerve and improve anesthesia success rates for third molar extraction: a randomized controlled trial and magnetic resonance imaging evaluation. J. Oral Maxillofac. Surg. 2019; 77: 2004–2016. PubMed Abstract | Publisher Full Text\n\nKim C, Hwang KG, Park CJ: Local anesthesia for mandibular third molar extraction. J. Dent. Anesth. Pain Med. 2018; 18: 287–294. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLago-Méndez L, Diniz-Freitas M, Senra-Rivera C, et al.: Postoperative recovery after removal of a lower third molar: role of trait and dental anxiety. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2009; 108: 855–860. PubMed Abstract | Publisher Full Text\n\nvan Wijk A , Lindeboom J: The effect of a separate consultation on anxiety levels before third molar surgery. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2008; 105: 303–307. PubMed Abstract | Publisher Full Text\n\nMatijević M, Uzarević Z, Gvozdić V, et al.: The influence of surgical experience, type of instructions given to patients and patient sex on postoperative pain intensity following lower wisdom tooth surgery. Acta Clin. Croat. 2013; 52: 23–28. PubMed Abstract\n\nChoi SH, Won JH, Cha JY, et al.: Effect of audiovisual treatment information on relieving anxiety in patients undergoing impacted mandibular third molar removal. J. Oral Maxillofac. Surg. 2015; 73: 2087–2092. PubMed Abstract | Publisher Full Text\n\nPatel RA, Wilson RF, Patel PA, et al.: The effect of smoking on bone healing: a systematic review. Bone Joint Res. 2013; 2: 102–111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMiroshnychenko A, Ibrahim S, Azab M, et al.: Acute postoperative pain due to dental extraction in the adult population: a systematic review and network meta-analysis. J. Dental Res. 2023; 102: 391–401. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTorof E, Morrissey H, Ball PA: The role of antibiotic use in third molar tooth extractions: a systematic review and meta-analysis. Medicina. 2023; 59: 422. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYousuf W, Khan M, Mehdi H, et al.: Necessity of antibiotics following simple exodontia. Scientifica. 2016; 2016: 1–6. Publisher Full Text\n\nAlshehri S, Alshehri T, AlMutiri H, et al.: data for patients participated to fill questionnaire that evaluate the knowledge and perceptions regarding third molar extraction. [Dataset]. figshare. 2024. Publisher Full Text\n\nAlshehri S, Alshehri T, AlMutiri H, et al.: Questionnaire regarding knowledge of third molar extraction. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "350574",
"date": "24 Jan 2025",
"name": "Ahmed Fadhel Al-Quisi",
"expertise": [
"Reviewer Expertise Oral and Maxillofacial Surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn scientific writing, terms like \"us,\" \"our,\" and \"we\" are considered first-person pronouns and should be avoided in scientific writing\n1-the title should clearly reflect this to inform readers about the timing of knowledge evaluation. Titles for such studies typically include phrases that highlight the timing (e.g., \"prior to,\" \"pre-extraction\") 2- the 6th paragraph of the introduction provides detailed information about Brasileiro B. et al.'s study who assessed patients’ preoperative, intraoperative, and postoperative perception while the current study discuss only preoperative perception. try to focus in the introduction about the value of prevoius studies and Avoid dedicating too much space to a single study 3- re-write of the rationale focusing on the gap in the literature and detailing the unique factors of the specific ethnic group the study investigated. 4- more detailed information regarding the sample size estimation 5- Including a copy of the questionnaire in the study is highly recommended for transparency and reproducibility 6- the time table for the study should be mentioned 7- the author mentioned (45% had previous wisdom tooth extraction experience, whereas 55% had no previous dental surgical expertise.) please specifiy what is the no previous dental surgical expertise. did you mean no previous lower third molar surgery ? 8-- how authors ensure accurate assessment of patient knowledge regarding wisdom tooth extraction, particularly for those requiring only simple extractions without flap reflection? 9- the conclusions should be re-written according to the statisitcal results of the study\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1376
|
https://f1000research.com/articles/13-1375/v1
|
18 Nov 24
|
{
"type": "Research Article",
"title": "Professional development for Indonesian elementary school teachers: Increased competency and sustainable teacher development programs",
"authors": [
"Rasmitadila .",
"Reza Rachmadtullah",
"Teguh Prasetyo",
"Megan Asri Humaira",
"Diah Andika Sari",
"Achmad Samsudin",
"Muhammad Nurtanto",
"Fitriyani .",
"Rohimi ZamZam",
"Reza Rachmadtullah",
"Teguh Prasetyo",
"Megan Asri Humaira",
"Diah Andika Sari",
"Achmad Samsudin",
"Muhammad Nurtanto",
"Fitriyani .",
"Rohimi ZamZam"
],
"abstract": "Background Various problems, such as a shortage of teachers, especially in certain outlying and underdeveloped provinces, unequal distribution of teachers, low teacher competency, and mismatch between educational qualifications and scientific fields, as well as the demands of increasingly dynamic developments in science and technology, resulting in the need for professional development for elementary school teachers to improve teacher professionalism in Indonesia. These background as a basis for the government to create teacher professional education program for elementary school teachers continuously. It is hoped that it will be able to answer the educational problems facing the Indonesian nation. This research explores the opinions of elementary school teachers who have participated in teacher professional development activities through the in-service teacher professional education program.\n\nMethods We collected data through a written survey of 24 elementary school teachers, as well as article documents relevant to the research topic. Data were analyzed using thematic analysis.\n\nResult The research produced two main themes: increasing teacher competencies and sustainable teacher development programs. Increasing teacher competency related to social competence, pedagogical competence and professional competence. The sustainable teacher development program is related to the guaranteeing the instructional quality of post-program and multi-sectoral collaboration\n\nConclusion Developing teacher professionalism through teacher professional education program in elementary schools in Indonesia positively impacts teachers’ becoming professional teachers. Teacher professional education program is an indication of improving teacher professionalism, especially in developing teaching skills, improving the quality of instruction, teacher motivation and individual development in dealing with various problems in instruction in the classroom, especially in elementary schools, so that the instructional objectives that have been set can be achieved. The professionalism of elementary school teachers will improve if there are sustainable programs such as mentoring programs from the government, universities and parties that focus on improving the quality of education in Indonesia",
"keywords": [
"Professional development",
"elementary school",
"professional teacher"
],
"content": "Introduction\n\nProfessional teachers in elementary schools are a significant need today to realize better quality education worldwide. Various elementary school teacher professional development (TPD) programs have been carried out in many countries to increase teacher competency in academic and non-academic fields, significantly improving student learning outcomes (Gümüş and Bellibaş 2023; Avalos 2011). TPD is a continuous process of learning, reflection, and action to improve teacher knowledge and skills, resulting in better teaching practices and positively impacting student learning (Luft and Hewson 2014; Singh, Rind, and Sabur 2021; Gafurov, Valeeva, and Kalimullin 2019). Several examples of TPD programs in elementary school which can be carried out through formal or non-formal means such as workshops, courses, seminars, degree programs, school observations, individual or collaborative research, peer-to-peer discussions or reading literature such as journal articles or theses are activities that teachers can choose and participate (OECD 2009). Through holistic and sustainable professional development of teachers throughout their careers, teachers are expected to develop individual, social, pedagogical and professional skills to provide meaningful learning to students up to the highest level of education, including teachers in elementary schools.\n\nThe professional development of elementary school teachers will directly impact students who face major learning challenges to achieve learning achievement. Teachers must be able to renew and hone their abilities to increase student success, so there is a need for effective TPD programs. The most effective form of TPD in elementary schools is proven by teaching coaching and collaboration between teachers who are adapted to developing the teacher’s personality in a special program (Porcell 2020; Botha and Herselman 2018; Lim, Juliana, and Liang 2020). TPD is an essential strategy in supporting the skills students need to prepare for further education in the 21st century (Twining et al. 2013; Martinez 2022). In the future, students must be able to master more challenging content, problem-solving, communication, and collaboration so that teachers must be able to answer these challenges with more sophisticated and practical learning. Collaboration between colleagues, the exchange of knowledge, as well as complementary competencies motivating teachers to develop continuously will be a challenge in solving learning problems in the classroom, so more professional elementary school teachers are needed (Van der Heijden et al. 2015; Bürgener and Barth 2018). The target for increasing teacher professionalism is, of course, the same as conditions in Indonesia.\n\nThe Indonesian government issued Law Number 14 of 2005 (Legislation 2005) concerning teachers and lecturers, and Article 1 Paragraph 1 states that teachers are professional educators with the main task of educating, teaching, guiding, directing, training, assessing, and evaluating students in early childhood education through formal education, primary education, and secondary education. Based on this law, currently in its implementation, a program was held to increase teacher professionalism, namely the teacher professional education program (TPEP). This program was created not only as a legal regulation but also because of various problems related to the professionalism of elementary school teachers and the quality of education in Indonesia. Various problems, such as a shortage of teachers, especially in certain outlying and underdeveloped provinces, unequal distribution of teachers, low teacher competency, and mismatch between educational qualifications and scientific fields, as well as the demands of increasingly dynamic developments in science and technology, resulting in the need for professional development for elementary school teachers. For this reason, the Indonesian government, through the Ministry of Education, Culture, Research and Technology, organizes TPEP for elementary schools in collaboration with higher education, which has study programs for TPEP, which are divided into two types, namely in-service and pre-service programs (Ministry of Education and Culture 2020). This program aims to ensure that elementary school teachers and prospective teachers carry out their professional duties responsibly and firmly, with discipline and mastery of the material, teach well, design learning, implement and evaluate learning, and develop themselves continuously.\n\nThis research explores elementary school teachers’ perspectives on teacher professional development through teacher professional education programs in Indonesia.\n\nTPD at the elementary school level refers to teacher development throughout their formal career by increasing knowledge, skills and competencies to create effective learning in the classroom. This professional development is the best practice in learning, such as handling students with various characteristics, involving parents and the community, including understanding legislation regarding the roles and responsibilities of teachers, and increasing teacher professionalism in the latest learning practices, including utilization of technology in learning. Through the development of teacher professionalism, it is hoped that there will be changes in the quality of learning, by: 1) changes in learning for the better, by implementing learning strategies effectively and efficiently; 2) support from all school members so that teachers continue to develop teacher potential, interests and talents so that they can achieve all school goals in the future; 3) teachers can develop themselves by understanding the characteristics of students from all cultural, economic and social backgrounds so that learning becomes better and of better quality; 4) teachers are given the opportunity to develop by applying an ever-evolving mindset, being able to face changes in classroom situations, so that they can train themselves in decision making and problem solving; 5) give opportunities for teachers to collaborate with other people, colleagues in developing critical ideas in solving problems in learning so that teachers have power creativity and innovation which continues to increase (Tam 2015).\n\nSeveral TPD programs in elementary schools in several countries have resulted in several views. In China, curriculum reform places TPD as an integral part of teacher practice as formulated in policy and its implementation. TPD programs in elementary schools in China are directed at 21st-century skills with a focus on increasing competence through inquiry-based learning (Kayange and Msiska 2016), one of which is research-oriented (Wang 2018). The Chinese government has issued various policies related to elementary school teacher professional programs, including collaboration between schools and universities, lesson planning collaboration, sharing about teaching practices, exchange programs, coaching colleagues, and research activities such as action research and reflection. Even though this program has received criticism from various parties, such as the focus on assessment and student learning outcomes, the TPD program in China is by 21st-century learning conditions because it prioritizes inquiry-based, critical, self-motivated learning and collaboration between school teachers. This condition is oriented towards the teacher’s work environment and development technology (Guo and Yong 2013).\n\nMeanwhile, the experience of TPD programs in the Philippines states that there is a need for professional elementary school teacher programs because teachers are seen as implementers of the curriculum, and the lack of teacher training has resulted in the development of leadership in schools (Alegado 2018). Another problem is the occurrence of emotional and work stress due to their work. This has implications on the spectrum of personal and professional development (Bongo and Casta 2017), so there is a need for TPD. Through TPD, teachers in the Philippines can develop TPD activities, whether carried out by schools or other parties, which can be done by attending seminars and continuing education at a higher level to develop their personal and professional competencies. Teachers want to gain new knowledge and skills according to student development through seminar activities or training on topics with relevant issues such as pedagogy, classroom management, technology, and assessment. In Malaysia, to improve the quality of education and human resources, TPD was started in 1995 by a committee specifically in the Ministry of Education. A few recommendations include encouraging teachers to take courses, continue their education, and study abroad to gain knowledge and education, in addition to pre-service training and in-service training for primary and secondary school teachers (Kabilan and Veratharaju 2013).\n\nThe European Commission’s policy emphasizes that TPD, including in elementary schools, consists of a 3-phase model: initial teacher education, induction (for new teachers, 3-5 years after graduation), and in-service teacher education to support teachers’ long-term career development. With this policy, European member states agree to continuous teacher education to ensure that initial teacher education, early career support, and further professional development are organized, regular, and highly quality (Commission of the European Communities 2007). Specifically in Finland, TPD programs are based on goal-oriented teacher leadership, school development, and quality teaching through collaboration and colleague interaction. TPD can be done through training and research. For example, in-service training in Finland is based on training time and short courses offered to teachers in a holistic and integrated manner so that teachers can design school-based projects and their development related to school development. Successful professional development of teachers in Finland also exists in collaboration with parents as external parties who provide full support, especially at the beginning of their career as teachers (Niemi 2015).\n\nMeanwhile, in the United States, most states require professional development and continuing education. Locally, schools provide opportunities for teachers to continue their education through professional development activities hosted by the school district (Wei, Darling-Hammond, and Adamson 2010). However, no national policy determines the content and methods of professional development programs. Development program activities can be carried out using short-term workshops, training, and master teacher programs that provide special training and financial incentives to participating teachers.\n\nElementary school teachers are educational personnel who will provide students with basic skills that will continue at the next level of education. For this reason, students’ best achievements will be significantly influenced by the professionalism of elementary school teachers in implementing all the skills they have. The Indonesian government pays special attention to the development of teacher professionalism, including elementary school teachers. This development commitment was issued by Law number 14 of 2005 in Article 1 Paragraph 1 concerning teachers and lecturers, which states:\n\n“Teachers are professional educators with the main task of educating, teaching, guiding, directing, training, assessing and evaluating students in early childhood education through formal education, basic education and secondary education.”\n\nThis law explains that the duties of teachers, including elementary school teachers, are very complex and focused on improving the quality of education in Indonesia. However, until now, the quality of education in Indonesia still needs to improve, and some of the problems are due to the low professionalism of teachers. This low level of professionalism is demonstrated, among other things, by the low level of teacher competence, such as pedagogical competence (World Bank 2015), even though the government has implemented various policies and increased educational investment to improve education quality. These results continue to be the basis for the government to create professional development programs for elementary school teachers continuously. The TPD program at elementary school began in 1980 with a teacher work consolidation program in the form of in-service training, which aimed to train teachers to practice student-centred instructional methods. In 1993, the Indonesian government created a similar program for elementary school teachers through teacher working groups. With the Teacher and Lecturer Law in 2005, the government developed a teacher certification program with a teacher professionalism program in teacher education and professional training. Some of these programs still need to improve classroom learning quality (Revina et al. 2020).\n\nThe government of Indonesia, through the Ministry of Education, Culture, Research and Technology, continues to develop professional teachers in the form of TPEP for elementary school teachers aimed at being designed systematically and by applying quality principles from the selection, learning, and assessment processes to competency tests, the aim is to develop future teachers who are professional and able to produce outstanding graduates. These graduates should be competitive, have strong character, and possess a love for their country. Additionally, the hope is that they will be able to address the educational challenges that the Indonesian nation is facing. The TPEP program is held after an undergraduate or applied undergraduate program, which demands different competency standards for graduates from an applied bachelor’s or bachelor’s program. TPEP graduate competency standards, which include attitudes, knowledge, and skills, are stated in learning outcomes. The TPEP is divided into two types, namely pre-service and in-service. Pre-service is an educational initiative held after completing an undergraduate or applied undergraduate program, open to Bachelor graduates from various backgrounds, both educational and non-educational, who are interested in becoming teachers (Ministry of Education and Culture 2020).\n\nThis program aims to obtain a special educator certificate in early childhood, primary, and secondary education. The benefits of pre-service are: 1) obtain an educator certificate; 2) improve pedagogical, social, professional and personality competencies to start a career as a professional teacher; 3) obtain recognition as a professional teacher. Meanwhile, in-service programs target elementary teachers currently active in educational institutions’ teaching profession. This program’s main focus is to improve teachers’ qualifications and abilities, aiming to become professional and superior educators in quality. Through this program, teachers can apply innovative teaching methods, encourage creativity, and improve student learning outcomes in elementary schools. This program also aims to increase teacher professionalism and provide a better understanding of the duties and responsibilities of a teacher.\n\nIn this research, we specifically explain in-service TPEP for elementary school teachers who have various materials and competencies related to the field of education, including pedagogy, educational psychology, educational management, and teacher professionalism. TPEP activities in this position are carried out over almost two months and take the form of 5 learning activities: 1) deepening the material in the field of expertise and pedagogy that will be taught; 2) development of learning tools; 3) practical field experience. The total credits taken in this program are 12 credits. In deepening the material, teachers will learn online for 5 credits. Learning activities aim to help teachers strengthen their understanding of professionalism, pedagogy, and subject matter by utilizing information and communication technology in online and independent learning through learning management systems (LMS) and other sources (Ministry of Education and Culture 2020).\n\nTo ensure teachers’ professionalism, it’s crucial for them to have an in-depth understanding of learning theories, educational psychology, sociocultural influences, social construction, and diversity. Expanding pedagogical expertise involves the careful planning, execution, and assessment of educational activities. The development of learning tools encompasses a 3-credit program aimed at assisting elementary school educators in creating effective learning tools through workshops that leverage their deep professional knowledge, pedagogical skills, and relevant areas of study. This includes curriculum analysis, designing educational activities, and crafting learning assessments using the Technological Pedagogical and Content Knowledge (TPACK) approach within the framework of Industry 4.0. The objective is to design educational activities and assessments that integrate critical thinking, creative thinking, reflective thinking, and decision-making skills through inquiry-based learning activities. Field experience practice activities with a credit load of 4 facilitate teachers to develop professional skills as teachers whose main task is to educate, teach, guide, direct, train, assess and evaluate students which is carried out as teaching practice.\n\nThis activity also facilitates teachers in carrying out non-teaching tasks in class and school administration, developing co-curricular and extra-curricular activities, and participating in other school activities. After implementing the three main activities, teachers will carry out performance exams and knowledge exams to measure and determine teacher performance achievements in planning, implementing and evaluating learning, as well as measuring and determining the level of teacher mastery of the field of study and pedagogy and deserving of educator certification.\n\n\nMethods\n\nTo explain the teacher’s professional development in elementary schools, we carried out a case study approach to allow researchers to obtain and examine data in a context or phenomenon in two ways. The first way was carried out using a written survey of 24 teachers who had implemented the in-service TPEP by the Ministry of Education, Culture, Research and Technology of the Republic of Indonesia in 2023. We also used documents from journals relevant to TPD, especially in Indonesia. Before participating in the study, participants were given complete information about the aims and procedures and provided written informed consent.\n\nThis research uses a purposive sampling strategy. The research location consists of 24 elementary schools in 3 provinces in Indonesia, namely Jakarta, West Java and East Java. The selection of elementary schools was based on the criteria of public and private schools with teachers who had completed a TPEP for almost two months. These schools are also for teachers who participate in the TPEP, where we are as tutors (TPEP’s educators). Meanwhile, teacher selection is based on the following criteria: 1) teachers with at least two years of teaching experience; 2) teachers who have participated in the in-service TPEP for almost two months. The research participants comprised 24 people (21 women and three men). They have teaching experience ranging from 2-30 years in elementary schools. They all had formal degrees (bachelor’s) before entering teaching careers. These teachers have been included in the criteria to see the impact of the TPEP that they have implemented, and are related to their teaching experience over a sufficient period of time, so that they can be used as participants in the research.\n\nData was collected in 2 ways; the first was using a survey with the help of Google Forms, which contained open questions consisting of 5 questions related to the implementation of the TPEP. Data collection was carried out over five days by providing a Google Form link to 24 teachers, and we monitored all teachers to ensure that they had filled in the link. The second way is to collect article documents that are relevant and specific to the results of professional teacher education programs using Google Scholar in Indonesia. We found 8 articles from national journals accredited by the Ministry of Education, Culture, Research and Technology of the Republic of Indonesia (Sinta) and DOAJ, Copernicus, Google Scholar, Scopus and Web of Science. The topics we collected from journal articles are related to TPD through TPEP, including the program’s impact, influence and effects. After data was collected from both data types, we began processing the data for data analysis. Data were analyzed using thematic analysis. We identify, evaluate and make the main themes revealed by researchers. In this analysis, we used an inductive method, coding both types of data, and to make it easier to create categorization and themes\n\nThe research and community service department of Universitas Djuanda has approved this research with the certificate number: 341/LPPM/K-X/X/2024 on February 8th 2024. The researcher gave a letter of approval has also been given by the researcher to all respondents. Written consent to participate from the respondent was obtained in accordance with document 01/K-X/IX/2024 on January 24th 2024. Respondents gave their consent without force from anyone. Subsequently, in order to protect the rights and privacy of the respondents, all forms of data acquired will remain confidential.\n\n\nResults\n\nThis study seeks to explore TPD through TPEP by examining elementary school teachers’ perspectives. For this purpose, teachers’ experiences related to professional development practices in the elementary school environment are explored. The themes resulting from data analysis consist of 2 main themes, namely increased competency and sustainable teacher development programs by Figure 1:\n\nIncreasing competency is related to increasing teacher ability and competency standards by objectives, job demands, and science and technology. The results of data analysis using interviews and journal articles on the theme of increasing competence consist of the sub-themes of social competence, pedagogical competence and professional competence. According to the findings regarding social competence, the teacher’s perspective consists of communication and adding colleagues. Communication between teachers and program participants increases motivation to carry out the program more enthusiastically at each stage, such as getting input using learning models, media, and assessments. With a grouping system consisting of 10-12 teachers from different schools, the teachers provide input and opinions to improve teacher competence during the program. The pattern of the program implemented by teachers increases bounding and cooperation so that they have friends who generally have the same problems, indicating that this program adds colleagues who support each other in improving competence. Several teachers explain this opinion:\n\n“For me, this program adds friends who can solve problems in class which are generally the same as how to choose a instructional model that suits our class.”\n\n“I practice my communication with my group friends, so that I gain experience in providing services to my students in class.”\n\nFor the sub-theme of pedagogical competence, the teachers’ opinions stated that with this program, they gained an understanding of meaningful learning, the use of learning tools, and the selection of learning strategies. According to teachers, understanding meaningful learning is achieved by mapping problems in the classroom. They can design learning according to student’s needs and choose methods and learning media that suit the characteristics of their students so that students get meaningful learning. One teacher explained this:\n\n“With this program, I am better prepared to prepare classes according to the characteristics of my students, so that learning is more meaningful.”\n\nThe use of learning tools is also one of the findings that teachers benefit. Teachers think that during the training program, making learning tools such as lesson plans that are appropriate to learning outcomes, learning reflections and examples of good practices that can be implemented in the classroom has a positive impact on teachers in improving learning designs in their classes, as well as understanding shortcomings when teaching. This opinion was explained by one of the teachers:\n\n“I came to understand how to create learning tools such as lesson plans and reflections so that I understand my shortcomings in teaching.”\n\nThe following finding regarding the selection of learning strategies according to teachers is how they determine learning strategies, such as using learning methods, using learning media that they can make manually or using technology. These learning steps are appropriate to their learning methods, to assessments that do not only use cognitive aspects but can assess all aspects (cognitive, affective, psychomotor). Choosing a learning strategy, according to the teacher, provides an opportunity for teachers to explore several varied learning methods that they have not only used so far, but by looking at their other colleagues, it becomes input for them in choosing an effective learning method for their class. This opinion was expressed by one of the teachers:\n\n“In this program, I was taught about choosing effective and best instructional methods according to the conditions of my class. I came to understand that there are many instructional methods and instructional media that I can use in my class.”\n\nIn the sub-theme of professional competence, findings consist of professional teachers, knowledge, understanding of technology, experience, and problem-solving solutions. Findings about professional teachers: Teachers hope they become more professional by better understanding education’s meaning through improving learning after the program. Meanwhile, science is related to additional new knowledge and broader thinking. Teachers get many benefits, especially expanding knowledge, such as the latest instructional methods from tutors and problem-solving methods that are always connected to effective thinking skills so that teachers gain broader insight into learning. One teacher stated:\n\n“Through this program, I have gained many benefits, especially increasing my knowledge, my insight has increased, especially how to solve the problems that I have been facing.”\n\nFindings regarding understanding technology are related to the use of technology, such as online meeting applications and operating applications for instruction, which aim to help teachers carry out tasks given by tutors and academic and non-academic tasks, such as online meeting applications. Because the teachers in this program are teachers in the senior category (mostly over 50 years old), this is a good achievement, especially in operating the internet and computer programs, which can support the smooth running of the program, as well as solving learning problems by using technology-based instructional media. The results of the article used in this research also showed that using technology in learning is one of the benefits of this professional teacher program. Meanwhile, the opinion of one teacher:\n\n“I was able to create my assignments using existing technology (Canva, AI, Infocus), which I rarely used in learning previously.”\n\nFrom the experience findings, the teacher believes that through professional development, teachers have added significant experiences for teachers. For example, teachers gain experience in designing instruction according to the characteristics of their students, which they have yet to do using initial stages such as mapping learning styles, class problems, especially subjects faced by students, and the real needs of students by predetermined learning outcomes. So far, they have always used instructional methods according to the teacher’s wishes, not the student’s (teacher-centred). Meanwhile, the findings regarding problem-solving in this subtheme are the methods teachers use related to learning difficulties, not achieving learning goals, and handling students with many characteristics. Through this program, teachers get many ways and choices in solving learning problems in the classroom, especially students’ learning difficulties. Teachers are starting to be able to design and choose instructional methods and media in the form of lesson plans for a limited duration or learning time, but with continuous practice, getting feedback from tutors, and revising them again so that they get maximum lesson plans have provided an in-depth experience that teachers can use when teaching in their classes. One teacher’s opinion:\n\n“In this program, I get attention and service from tutors in designing lessons, for example. We will design a lesson plan, revise it and get the best feedback that we can practice in our class according to the characteristics of the students.”\n\nThe theme of the sustainable teacher development program is related to the two sub-themes of guaranteeing the instructional quality of post-program and multi-sectoral collaboration. The sub-theme guarantee of the instructional quality of post-program is related to monitoring the quality of learning and special teacher programs. Findings regarding monitoring the quality of learning are after the TPEP. In several articles analyzed, monitoring the quality of instruction after the program is necessary because it affects the overall quality of education. The teacher’s opinion states that there must be a special program after the program so that the teacher’s enthusiasm and motivation to improve the quality of instruction is higher. Teachers also think that the government should be able to provide scheduled special programs, for example, teacher meetings in certain periods on certain topics that can maintain the quality of teacher learning, information on instructional methods, and the latest learning applications. One teacher stated:\n\n“I hope that there will be a scheduled follow-up program that can be facilitated by the education department, for example, which can give teachers the opportunity to update their knowledge regularly, so that the quality of instruction can continue to improve.”\n\nMeanwhile, the findings of the multi-sectoral collaboration subtheme relate to the need for collaboration between the government, educational institutions (universities), schools, and the community in supporting professional teacher education programs, especially post-program. The government must be able to embrace all parties to be involved in improving the quality of education. Support from all sectors can improve educational services because the quality of instruction will improve due to the implementation of professional teacher programs in elementary schools. With the involvement of all sectors and all parties, for example, parents can evaluate the quality of instruction through the school committee regarding the learning outcomes students achieve each semester.\n\n\nDiscussion\n\nIn this research, we conducted a written survey of teachers who had implemented TPD through TPEP at elementary schools, and we used article documents relevant to the research topic. We analyzed both types of data based on theoretical background and research findings in teacher professional development. The development of teacher professionalism at the elementary school level, organized by the Ministry of Education, Culture, Research and Technology of the Republic of Indonesia, is a mandatory program for teachers through the TPEP. This research shows that it is essential to develop teacher professionalism in scheduled programs included in the national and other informal programs. In particular, TPD through TPEP can improve teacher competency, which is expected to be implemented sustainably in other formal and informal programs. Overall, we succeeded in finding a theme for a professional teacher with two main themes, which emphasized competency and sustainability programs for teachers so that the quality of instruction is maintained well after the professional teacher program. We identified two the main themes that are very important for achieving teacher professionalism, especially in elementary schools in Indonesia.\n\nFirst, increasing teacher competency is the main requirement for teachers in solving instructional problems in elementary school classes. In the TPEP, there are four standard competencies that teachers must have, namely personal, professional, pedagogical and social competencies. We found only the three most dominant competencies in this research, namely social, pedagogical and professional competencies. Social competence refers to the teacher’s ability to communicate and get along with colleagues, education staff, students, parents, and the community. In this program, all activities are done in one group with the same goal. Therefore, communication between teachers and tutors, a sense of having the same goals, and helping each other academically and non-academicly greatly impact teachers’ achievements (Atawolo and Hartoyo 2023). The results of the instructional design that has gone through a process with colleagues and tutors in providing constructive input also make it easier for teachers to implement it with students in the classroom. Good communication with colleagues motivates teachers to communicate and interact well with students (Robinson 2022; Iurea 2015).\n\nIncreasing pedagogical competence is a teacher’s ability to understand students, design and implement instruction, develop students, and evaluate student learning outcomes to actualize their potential (Shernoff et al. 2017; Caena and Redecker 2019). In this TPEP, we see that the process in each stage carried out by teachers begins with mapping the instructional problems in the classroom for each teacher. Teachers must systematically understand the problems that have been obstacles to achieving learning goals with various student characteristics. The problems found are analyzed and included in the instructional planning, which will then be implemented in the class, and the tutor will evaluate their achievements. The steps in each stage of the program, such as deepening the material, developing learning tools, and field practice (classroom practice), are the latest knowledge and insights obtained by teachers. With this experience, teachers gain ways to design effective instruction, understand students’ potential and understand the strengths and weaknesses of teachers they need to learn. Teachers can develop the latest instructional methods according to class characteristics, using instructional media and technology to make instruction more interesting and enjoyable for students (Tang and Austin 2009; Haleem et al. 2022). In contrast, all students can achieve learning achievements. For example, teachers in this program use problem-based learning (PBL) methods to solve learning problems in the classroom. Teachers learn about the benefits and objectives of PBL so that learning outcomes exceed the expectations that teachers have previously lacked.\n\nMeanwhile, increasing professional competence is a teacher’s mastery of learning material broadly and deeply, both curriculum material, subjects and the substance of knowledge that covers the instructional material (Kartini et al. 2020; Davis, Janssen, and Van Driel 2016). With an academic background - not from an elementary school teacher program - the TPEP provides new knowledge for teachers, as provided by university tutors with expertise and research results relevant to teacher professional development. Tutors and teachers discuss competency standards that students must achieve comprehensively from cognitive, affective and psychomotor aspects, which teachers and colleagues rarely do. This becomes input for teachers in developing lesson materials to be more systematic, understanding the relationships between materials, sorting materials from simple to complex, and even creating additional teaching materials if students need special time to understand certain materials.\n\nSecond, the sustainable teacher development program is the hope of teachers that the elementary school TPEP is only one way for the government to increase teacher professionalism in Indonesia. We see the need for a similar program that is sustainable and scheduled to renew the competence of teachers who have taken part in this teacher professional development. Professional development of elementary school teachers is an activity that increases teacher motivation in teaching and enthusiasm for improving the quality of education, especially in Indonesia (Sumantri and Whardani 2017; Bernat 2010). Routine activities initiated by the education department, school community, or teacher community with formal and informal beneficial activities, such as discussing literature or discussing the latest instructional methods with colleagues, can maintain teacher motivation so that they remain enthusiastic about improving their personal skills. Apart from that, attending seminars and educational workshops organized by the government or other parties can also maintain the positive impact that teachers have received after the TPEP. For this reason, it is necessary to involve all parties in developing the professionalism of elementary school teachers (Fuadi, Nasution, and Wijaya 2023; Agustina, Suriansyah, and Asniwati 2021). The government can collaborate with other parties, such as the private sector or other bodies, to implement advanced programs that motivate teachers to become more professional.\n\n\nConclusion\n\nDeveloping teacher professionalism through TPEP in elementary schools in Indonesia positively impacts teachers’ becoming professional teachers. Increasing teacher competence is an indication of improving teacher professionalism, especially in developing teaching skills, improving the quality of instruction, teacher motivation and individual development in dealing with various problems in instruction in the classroom, especially in elementary schools, so that the instructional objectives that have been set can be achieved. The professionalism of elementary school teachers will improve if there are sustainable programs such as mentoring programs from the government, universities and parties that focus on improving the quality of education in Indonesia.\n\n\nEthics and consent\n\nThe research and community service department of Universitas Djuanda has approved this research with the certificate number: 341/LPPM/K-X/X/2024 on February 8th 2024. The researcher gave a letter of approval has also been given by the researcher to all respondents. Written consent to participate from the respondent was obtained in accordance with document 01/K-X/IX/2024 on January 24th 2024. Respondents gave their consent without force from anyone. Subsequently, in order to protect the rights and privacy of the respondents, all forms of data acquired will remain confidential.",
"appendix": "Data availability statement\n\nFigshare: ‘Professional development for Indonesian elementary school teachers: Increased competency and sustainable teacher development programs’ Doi: https://doi.org/10.6084/m9.figshare.27141483.v3 (Rasmitadila et al., 2024a)\n\nThis project contains the following underlying data:\n\n• Data Sheet-TPEP (2).numbers\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Journal contribution. Doi: https://doi.org/10.6084/m9.figshare.27225480.v1 (Rasmitadila et.al., 2024b)\n\nThis project contains the following extended data:\n\n• Journal Contribution.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAgustina F, Suriansyah A, Asniwati: Teacher Professionalism Development. Journal of K6 Education and Management. 2021; 4(2): 207–216. Publisher Full Text\n\nAlegado PJE: The Challenges of Teacher Leadership in the Philippines as Experienced and Perceived by Teachers. International Journal of Educational Research. 2018; 6(6): 291–302.\n\nAtawolo BG, Hartoyo A: THE APPLICATION OF PRINCIPAL LEARNING LEADERSHIP IN IMPROVING TEACHER PROFESSIONALISM AT BRODER KANISIUS PONTIANAK ELEMENTARY SCHOOL. Journal of Educational Learning and Innovation (ELIa). 2023; 3(2): 414–430.\n\nAvalos B: Teacher Professional Development in Teaching and Teacher Education over Ten Years. Teaching and Teacher Education. 2011; 27(1): 10–20.\n\nBernat E: The Asian EFL Journal Quarterly.2010.\n\nBongo R, Casta J: Emotional and Occupational Stress among Teachers in Tagum North District, Philippines. Philippines (January 2, 2017). 2017.\n\nBotha A, Herselman M: Teachers Become Cocreators through Participation in a Teacher Professional Development (TPD) Course in a Resource Constraint Environment in South Africa. The Electronic Journal of Information Systems in Developing Countries. 2018; 84(1): e12007.\n\nBürgener L, Barth M: Sustainability Competencies in Teacher Education: Making Teacher Education Count in Everyday School Practice. Journal of Cleaner Production. 2018; 174: 821–826.\n\nCaena F, Redecker C: Aligning Teacher Competence Frameworks to 21st Century Challenges: The Case for the European Digital Competence Framework for Educators (Digcompedu). European Journal of Education. 2019; 54(3): 356–369.\n\nDavis EA, Janssen FJJM, Van Driel JH: Teachers and Science Curriculum Materials: Where We Are and Where We Need to Go. Studies in Science Education. 2016; 52(2): 127–160.\n\nFuadi A, Nasution WN, Wijaya C: Management of Teacher Professionalism Development: A Multi-Site Study of State Madrasah Aliyah in Langkat Regency. Tafkir: Interdisciplinary Journal of Islamic Education. 2023; 4(1): 180–199. Publisher Full Text\n\nGafurov I, Valeeva R, Kalimullin A: Teachers’ Professional Development in Global Contexts. Образование и Саморазвитие. 2019; 14(3): 6–10.\n\nGümüş E, Bellibaş MŞ: The Relationship between the Types of Professional Development Activities Teachers Participate in and Their Self-Efficacy: A Multi-Country Analysis. European Journal of Teacher Education. 2023; 46(1): 67–94.\n\nGuo KL, Yong Y: Policies and Practices of Professional Development in China: What Do Early Childhood Teachers Think? Australian Journal of Teacher Education. 2013; 38(6). Publisher Full Text\n\nHaleem A, Javaid M, Qadri MA, et al.: Understanding the Role of Digital Technologies in Education: A Review. Sustainable Operations and Computers. 2022; 3: 275–285.\n\nIurea C: Classroom Environment between Stimulation and Discouragement. Teacher’s Contribution to Creating a New Socio-Affective Environment Favoring the Teacher-Student Communication. Procedia - Social and Behavioral Sciences. 2015; 203: 367–373.\n\nKabilan MK, Veratharaju K: Professional Development Needs of Primary School English-Language Teachers in Malaysia. Professional Development in Education. 2013; 39(3): 330–351. Publisher Full Text\n\nKartini D, Kristiawan M, Happy Fitria S, et al.: The Influence of Principal’s Leadership, Academic Supervision, and Professional Competence toward Teachers’ Performance. International Journal of Progressive Sciences and Technologies (IJPSAT). 2020; 20(1): 156–164.\n\nKayange JJ, Msiska M: Teacher Education in China: Training Teachers for the 21st Century. The Online Journal of New Horizons in Education. 2016; 6(4): 204–210.\n\nLegislation: Undang-Undang (UU) Nomor 14 Tahun 2005 Tentang Guru Dan Dosen. Government of the Republic of Indonesia; 2005. 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Paris: OECD; 2009.\n\nPorcell MA: Veteran Elementary Teachers’ Perceptions about Teacher Professional Development: A Phenomenological Study.2020.\n\nRasmitadila R, Rachmadtullah R, Prasetyo T, et al.: Professional development for Indonesian elementary school teachers: Increased competency and sustainable teacher development programs (Version 3). figshare. 2024a. Publisher Full Text\n\nRasmitadila R, Rachmadtullah R, Prasetyo T, et al.: Journal contribution (Version 1). figshare. 2024b. Publisher Full Text\n\nRevina S, Pramana RP, Fillaili R, et al.: Systemic Constraints Facing Teacher Professional Development in a Middle-Income Country: Indonesia’s Experience Over Four Decades. Research on Improving Systems of Education (RISE); 2020. Publisher Full Text\n\nRobinson CD: A Framework for Motivating Teacher-Student Relationships. 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Teachers and Teaching. 2015; 21(1): 22–43.\n\nTang TL-P, Austin MJ: Students’ Perceptions of Teaching Technologies, Application of Technologies, and Academic Performance. Computers and Education. 2009; 53(4): 1241–1255.\n\nTwining P, Raffaghelli J, Albion P, et al.: Moving Education into the Digital Age: The Contribution of Teachers’ Professional Development. Journal of Computer Assisted Learning. 2013; 29(5): 426–437.\n\nVan der Heijden HRMA, Geldens JJM, Beijaard D, et al.: Characteristics of Teachers as Change Agents. Teachers and Teaching. 2015; 21(6): 681–699.\n\nWang T: School Leadership and Professional Learning Community: Case Study of Two Senior High Schools in Northeast China. Global Perspectives on Developing Professional Learning Communities. Routledge; 2018; 10–24.\n\nWei RC, Darling-Hammond L, Adamson F: Professional Development in the United States: Trends and Challenges.2010.\n\nWorld Bank: Indonesia Teacher Certification and Beyond: An Empirical Evaluation of the Teacher Certification Program and Education Quality Improvements in Indonesia. Jakarta: World Bank; 2015. Reference Source"
}
|
[
{
"id": "357153",
"date": "06 Feb 2025",
"name": "Yifan Ou",
"expertise": [
"Reviewer Expertise psychology",
"communication and mental health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nStrengths\nRich and Relevant Research Background: The article provides a detailed overview of the current state and significance of Teacher Professional Development (TPD) on a global scale, with a particular focus on Indonesia's Teacher Professional Education Program (TPEP). The background information is comprehensive, allowing readers to quickly understand the necessity and urgency of the research. It emphasizes the crucial role of primary school teacher professional development in improving student learning outcomes and addressing the challenges of 21st-century education, aligning with current hot topics in the field of education.\nRigorous Research Methodology: The study employs a case study approach, combining surveys and literature analysis, with diverse data sources that support the research conclusions from multiple perspectives. Thematic analysis is used to process the data, which is a scientific and rational method that helps extract valuable information from a large amount of data. The research clearly outlines ethical considerations, including obtaining approvals and informed consent from participants, in line with basic academic standards.\nSystematic and Comprehensive Research Content: The article offers a detailed comparative analysis of the current state of primary school teacher professional development across different countries, providing an international perspective and highlighting the uniqueness and借鉴意义 of Indonesia's TPEP. It delves into the specific content, goals, implementation methods, and participants of TPEP, covering multiple aspects of teacher professional development.\nInspiring Research Findings: Two main themes are identified—enhancing teacher competence and sustainable teacher development programs—which offer valuable insights for primary school teacher professional development in other countries and regions. The rich and diverse feedback from teachers reflects the actual impact of TPEP on their professional growth, enhancing the credibility of the research. -------------------------\nWeaknesses\nLimited Research Sample: The study only includes 24 primary school teachers from three provinces in Indonesia. The small sample size and limited geographical scope may not fully represent the situation of primary school teachers nationwide, restricting the generalizability of the research findings.\nMethodological Limitations: Although surveys and literature analysis are used, the surveys are conducted solely through Google Forms, which may limit the ability to gain in-depth insights into teachers' complex views and emotional experiences. There is a lack of direct observation or case analysis of classroom practices, making it difficult to comprehensively assess the direct impact of TPEP on teachers' actual teaching behaviors and student learning outcomes.\nNeed for Deeper Analysis: The discussion section provides a relatively brief analysis of the research findings, lacking in-depth theoretical exploration and comparative analysis with other studies. The reasons for the success or shortcomings of TPEP are not thoroughly examined. The specific implementation suggestions for sustainable teacher development programs are not detailed enough, lacking actionable plans and predictions of expected outcomes.\nInsufficient Timeliness and Comprehensiveness of Literature Review: Some of the cited literature is outdated, which may fail to cover the latest research findings and trends. The analysis of primary school teacher professional development programs in other countries is not in-depth enough, lacking a summary and comparison of lessons learned from different countries. This makes it difficult to highlight the unique advantages and areas for improvement of Indonesia's TPEP. ---------------------------------\nRevision Suggestions\nDeepen Theoretical Analysis: Strengthen the theoretical interpretation of research findings in the discussion section, integrating relevant domestic and international theories and the latest research results to deeply analyze the successful experiences and shortcomings of TPEP.\nImprove Literature Review: Update and supplement the latest literature, especially cutting-edge international research on primary school teacher professional development, to enhance the academic and forward-looking nature of the study.\nOverall, the article has certain academic value and potential for getting approved for indexing, but there is room for improvement in terms of research depth, breadth, and methodology.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1375
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https://f1000research.com/articles/13-1369/v1
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15 Nov 24
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{
"type": "Research Article",
"title": "Financial inclusion and stability in Ethiopia using bank-level data: A two-step system GMM estimation",
"authors": [
"Mohammed Arebo",
"Filmon Hando",
"Andualem Mekonnen",
"Filmon Hando",
"Andualem Mekonnen"
],
"abstract": "Background This paper examines the impact of financial inclusion on bank stability within Ethiopian context, using panel data from 17 commercial banks over the period 2015-2023. Given the scarcity of research focused on the relationship between financial inclusion and bank stability in Ethiopia, this paper seeks to address a crucial gap by analyzing both conventional and digital aspects of financial inclusion in relation with bank stability.\n\nMethods A two-stage principal component analysis (PCA) was conducted to construct a composite financial inclusion index, integrating 10 conventional and 5 digital indicators. The study applied a two-step robust system generalized method of moments (GMM) to examine the effects of financial inclusion on bank stability, complemented by Granger causality testing to examine the directionality of this relationship.\n\nResults The result reveals a significant positive effect of financial inclusion on bank stability and Granger causality tests confirms a bi-directional relationship between financial inclusion and stability, indicating that improvements in financial inclusion foster greater stability and vice versa. Our results also highlight that while bank efficiency and GDP growth rate positively effect stability, total assets and income diversification exhibit detrimental effects.\n\nConclusions It is essential to capitalize policy synergies to promote bank stability and to enhance financial inclusion through conventional and digital channels, while carefully managing the implications of risks associated with income diversification and asset distribution. Ensuring inclusive financial system is vital for maintaining bank stability, thus positioning it as a key priority for financial institutions.",
"keywords": [
"Financial Inclusion",
"Principal Component Analysis",
"Bank stability",
"GMM",
"Ethiopia"
],
"content": "1. Introduction\n\nIn contemporary financial policymaking, the pursuit of financial system stability has increasingly been viewed in alongside with the promotion of financial inclusion (FI) (Antwi et al., 2024; Arora, 2020). Growing evidence suggests that the degree of FI can siginificantly impact the stability of financial systems (Damane & Ho, 2024; Antwi et al., 2024; Vo et al., 2020; Kim et al., 2020; Ahamed & Mallick, 2019). Historically, the dominant focus of financial authorities was primarily on preserving financial stability (Schinasi, 2005). However, over recent decades, FI has risen to prominence as a key policy goal, complementing the objectives of stability, integrity, and consumer protection, largely driven by the initiatives of global regulatory bodies and stakeholders (Hannig & Jansen, 2010). This shift prompts a critical inquiry into whether financial stability and FI function as substitutes or complements within the broader regulatory framework (Morgan & Pontines, 2017).\n\nThis research investigates the impact of FI on bank stability, focusing on Ethiopia to address existing literature gaps. Bank stability, characterized by the absence of crises within the sector, is essential for maintaining public confidence and ensuring the effective execution of financial intermediation tasks (Schinasi, 2004). The determinants of bank stability can differ significantly across various contexts, requiring tailored policy responses (Ozili, 2018). Factors influencing bank stability include internal elements such as general ledger (GL) and profit-loss (PL) accounts, as well as external socio-economic and political conditions (Ha & Nguyen, 2023). FI, which encompasses improvements in accessibility, quality, quantity, and efficiency of financial services (Pesqué-Cela et al., 2021; Demirgüç-Kunt et al., 2017; Allen et al., 2016; Babajide et al., 2015), has been demonstrated to enhance livelihoods, create opportunities, and bolster economies (Le et al., 2019).\n\nEmpirical studies on the impact of FI on bank stability in developing countries is scarce (Chinoda & Kapingura, 2023; Koudalo & Toure, 2023; Jungo et al., 2022). Neglecting this relationship could lead to severe consequences, including costly financial crises or ongoing financial exclusion (Danisman & Tarazi, 2020; Čihák et al., 2016). Schoenmaker (1996) highlights that failures within individual financial sectors can trigger contagion effects, leading to widespread instability stemming from the collapse of financial institutions. In such scenarios, a single institution's failure can create a ripple effect, eroding investor confidence and prompting a rush to liquidate deposits (Huynh et al., 2020). Therefore, understanding contagion risk is crucial for comprehending the dynamics of the financial system and its stability (Huynh et al., 2020). Consequently, policymakers must adeptly balance the trade-offs and synergies between fostering FI and maintaining stability (Damane & Ho, 2024; Čihák et al., 2016).\n\nIn Ethiopia, while several studies have been conducted in relation to financial sector stability (Filatie & Sharma, 2024; Kebede et al., 2024; Fisseha, 2023; Yitayaw et al., 2023; Dress, 2022; Abdu, 2021; Isayas & McMillan, 2021; Aman, 2019; Meher & Getaneh, 2019; Zelie & Wassie, 2019; Meressa, 2018), the impact of FI on bank stability remains largely unexplored. Additionally, recent data underscore significant disparities in financial service provision, with loan disbursement heavily concentrated in urban areas (99.8%) and a troubling concentration of loans among the top ten borrowers, who hold 23.5% of all outstanding loans (NBE Financial Stability Report, 2024), highlight the need for a thorough examination of how FI effect bank stability.\n\nTo the best of the researchers' knowledge, no prior study has examined the effect of FI on bank stability in Ethiopia. This study makes several contributions. First, it constructs a composite FI index using two-stage PCA, incorporating both conventional and digital dimensions. Second, it applies the two-step robust system GMM estimator to examine the impact of FI on bank stability while addressing endogeneity concerns. Third, it employs panel causality tests, including those by Juodis et al. (2021) and Dumitrescu and Hurlin (2012), to determine the causal direction between FI and stability. Finally, the study offers actionable insights for policymakers, guiding strategies to enhance both FI and financial stability in Ethiopia.\n\nThe remainder of the study is structured as: Part 2 reviews the literature; Part 3 details the data sources and econometric methods; Part 4 presents and discusses the empirical results; and Part 5 concludes with key findings and policy implications.\n\n\n2. Literature review\n\nFI, from a macroeconomic perspective, is seen as a catalyst for “creative destruction,” promoting economic growth, reducing inequality, and enhancing financial stability. However, at the micro level, excessive FI can lead to opportunistic behaviors, such as fund misuse and deliberate payment delays, which may undermine financial stability (Hua et al., 2023). The impacts of FI are neither uniform nor static; they vary across different temporal and spatial contexts. This has led to divergent views among researchers regarding its impact on bank stability, with two divergent schools of thought emerging as the one positing a FI-stability effect and the other suggesting a FI-instability outcome (Damrah et al., 2023; Moaz, 2022). To that end, the relationship between FI and bank stability has become a central theme in both academic and policy discourse (Čihák et al., 2016). This study employs a multi-theoretical approach, drawing on asymmetric information theory, financial intermediation theory, systemic risk theory, and portfolio theory. These theoretical underpinnings collectively offer a nuanced understanding of the pathways through which FI can effect bank stability in Ethiopia.\n\nAsymmetric information theory, highlighted by Akerlof (1970), addresses the challenges posed by uneven information distribution in financial markets. In FI, this imbalance is particularly significant as institutions serve previously unbanked populations. Difficulties in assessing creditworthiness can lead to adverse selection, hindering credit risk management and operational efficiency, which may compromise financial stability (Oanh et al., 2023; Moaz, 2022; Sethy & Goyari, 2022; Barik & Pradhan, 2021; Khan, 2011; Bofondi & Gobbi, 2003). Balancing information asymmetry within FI context can thus strengthen the financial system.\n\nThe financial intermediation theory underscores the pivotal role of banks in linking savers with borrowers (Scholtens & Wensveen, 2003; Diamond, 1984), thereby facilitating FI. By providing liquidity, managing risks, and bridging informational gaps, banks contribute to the efficient allocation of capital and the mitigation of risks, which enhances overall financial stability (Servigny & Renault, 2004). This theory emphasizes that by expanding financial access, particularly in developing economies where financial exclusion is significant, banks can improve their performance by broadening their customer base, increasing deposits, and fostering a more resilient financial system (Kim et al., 2018; Diamond, 1984). This phenomenon lessens information asymmetry, thereby lessens market imperfections (Oanh et al., 2023).\n\nSystemic risk theory, as developed by Minsky (1982) and later refined by Borio (2011), addresses the interconnectedness of financial institutions and the amplification of shocks through mechanisms such as leverage, asset price bubbles, and procyclicality. Borio differentiates systemic risk into temporal and cross-sectional dimensions. Temporal risk involves the dynamic evolution of aggregate risk, while cross-sectional risk pertains to the distribution of risk within the financial system, influenced by common exposures and counterparty risks. Within the context of FI, Khan (2011) suggests that expanding borrower bases can lower lending standards, potentially destabilizing the financial system. Conversely, Hannig and Jansen (2010) argue that FI can enhance stability by diversifying deposit and loan bases, involving segments less susceptible to economic cycles, while Prasad (2010) highlights the positive effects of credit access on employment and economic growth.\n\nPortfolio theory highlights the significance of diversification in mitigating risk (Markowitz, 1952). In the context of FI, a diversified loan portfolio can potentially reduce the impact of credit losses on individual banks and the overall financial system (Beck et al., 2013; Wang & Lin, 2021). Adem (2022) concurs, noting that diversification lowers bankruptcy risk for banks. Khan (2011) outlines three main ways of mitigating the FI on financialinstability: diversification of bank assets through increased lending to smaller firms reduces portfolio risk; an expanded and stable deposit base lessens reliance on volatile non-core financing; and improved monetary policy transmission enhances stability. However, as Huynh & Dang (2021) argue, the effectiveness of diversification hinges on the correlation between loan segments and the portfolio's overall risk profile.\n\nDrawing on these theoretical foundations, this study offers a unique lens through which the impact of FIonbank stability can be comprehended. The theories collectively guide our understanding of how FI initiatives can be designed to support the broader financial servicesaccess and the long-term stability of the financial system.\n\nEmpirical research regarding the impact of FI on the stability of financial systems presents varied outcomes (Damrah et al., 2023; Feghali et al., 2021; Vo et al., 2020). Despite data limitations, these studies provide perspectives on both the positive and negative effects of FI on the stability of banks.\n\n2.2.1 Positive impact of financial inclusion on bank stability\n\nWang and Luo (2022), using data from over 1500 commercial banks across 36 emerging economies, found that FI significantly enhances bank stability by promoting operational efficiency, risk management, and funding stability. Similarly, Nguyen and Du (2022), employing System GMM for 102 banks in six ASEAN countries, concluded that FI promotes stability through increased customer deposits and reduced non-performing loans (NPLs). Their findings align with those of Morgan and Pontines (2017), who showed that lending to small and medium sized enterprises (SMEs) diversifies risk and contributes to higher Z-scores and lower NPL ratios, key indicators of bank stability. These studies collectively highlight how extending credit to SMEs serves as a buffer against financial instability by diversifying loan portfolios and reducing concentrated risk exposure.\n\nAhamed and Mallick (2019) extended this argument by analyzing a global dataset of 2635 banks in 86 countries. Using two-step system GMM, they posited that FI enhances stability by increasing customer deposits and lowering marginal banking costs, with the effectiveness of these benefits being contingent on institutional quality. They highlight the role of a robust institutional framework in ensuring that FI does not devolve into unchecked risk-taking. In this context, the study implicitly warns against viewing FI initiatives in a silo, devoid of regulatory oversight or institutional support. Similarly, Hannig and Jansen (2010) emphasized the role of robust institutional frameworks in ensuring that FI initiatives do not lead to unchecked risk-taking, a finding also supported by Sethy and Goyari (2022) in their study of South Asian countries, where FI was found to be a key driver of long-term stability.\n\nVo et al. (2020) and Chinoda and Kapingura (2023) both underscore the importance of FI in reducing systemic risks. Vo et al. (2020) highlight its role in broadening the depositor base and improving financial resilience in emerging markets, while Chinoda and Kapingura (2023) emphasize the stabilizing effects of digital FI in Sub-Saharan Africa, noting that it significantly reduces NPLs and enhances bank stability. Another layer of analysis emerges in the work of López and Winkler (2019), who explore FI during periods of financial crises using 189 economies data for the period of 2004–2017. Their study finds that countries with higher levels of FI experience less severe disruptions in credit availability during economic downturns. Similarly, Pham and Doan (2020), examining 42 countries across Asia using Feasible Generalized Least Squares (FGLS), conclude that even a weak positive impact of FI on stability is enough to safeguard financial markets against extreme volatility, especially when FI fosters a stable retail deposit base.\n\nIn the MENA region, Neaime and Gaysset (2018) demonstrated that FI contributes positively to stability by reducing income inequality. This finding is echoed by Malik et al. (2022), who showed that in Asian countries, FI mediates the relationship between governance quality and financial stability, further emphasizing its stabilizing potential when integrated with good governance practices. Similarly, Koudalo and Toure (2023), using Fixed Effect and GMM models for 54 African countries, found a positive association between account penetration, a key measure of FI, and stability, particularly under conditions of income equality, political stability, and financial openness.\n\nKhan (2011) and Čihák et al. (2016) underscore the critical role of institutional quality and regulation in mediating the relationship between FI and stability. Khan (2011) identified three key channels: asset diversification, the inclusion of small depositors, and enhanced monetary policy transmission. Čihák et al. (2016) found that FI strengthens stability in countries with robust supervisory frameworks. These insights suggest that FI must be part of a comprehensive approach to financial stability, integrating regulatory quality, institutional capacity, and risk management. Dienillah et al. (2018), using a Tobit model for 19 countries from 2004 to 2014, revealed that FI positively impacts stability in high-income nations but shows insignificant effects in lower-income groups. This highlights the need for tailored FI strategies suited to specific economic and regulatory environments. Jungo et al. (2022) further emphasize the importance of expanding financial access and encouraging investment in FI to maintain monetary system stability, particularly in developing countries.\n\n2.2.2 Negative impact of financial inclusion on bank stability\n\nDamrah et al. (2023) present a nuanced view of FI’s impact on bank stability in Kuwait from 2003 to 2017, illustrating how inclusion can have both positive and negative effects depending on the type of bank (Islamic vs. conventional) and external factors such as financial crises. Their Linear Mixed Model (LMM) reveals that while FI improves access to services, it also introduces inefficiencies and increased risk exposure, particularly during times of economic distress. Their findings align with those of Barik and Pradhan (2021), who, using system-GMM estimators for BRICS nations from 2005 to 2015, argue that rapid credit expansion facilitated by FI can deteriorate lending standards and escalate non-performing loans (NPLs).\n\nEmploying System GMM ranging from 2011-2019, Umar and Akhtar (2024), examining Chinese banks, found that while FI generally reduces bank risk-taking, it can increase risks in unlisted and large banks, suggesting that the impact of FI varies depending on bank characteristics. Similarly, Le et al. (2019), using Feasible Generalized Least Squares (FGLS), highlight the trade-offs associated with FI, noting that while FI promotes financial sustainability, it also negatively impacts financial efficiency due to the operational challenges of servicing previously unbanked populations. Hua et al. (2023) extend this argument by proposing an inverted U-shaped relationship between FI and financial stability, demonstrating that beyond a certain threshold, further inclusion can destabilize the financial system, particularly in countries with weak regulatory environments.\n\nKebede et al. (2021) further emphasize the intricate nature of FI in Africa, noting that its benefits may be limited by high market concentration, which can stifle competition and reduce the effectiveness of inclusion efforts. This view is echoed by Oanh et al. (2023) and Jima and Makoni (2023), who highlight the contextual nature of FI’s impact. Employing panel vector autoregression (PVAR) model for 58 countries (27 low financial development states and 31 high financial development states) from 2004 to 2020, Oanh et al. (2023) found that FI positively correlates with stability in low-financial-development countries, but this relationship turns negative in more developed financial systems, where excessive credit access may heighten systemic risks. Similarly, Jima and Makoni (2023), using ARDL cointegration and Granger causality tests from 2000 to 2019 for 26 Sub-Saharan African countries, revealed that while FI contributes to both short-term and long-term stability, the relationship is bidirectional and contingent on broader economic and institutional conditions. In addition, Damane & Ho (2024) and Čihák et al. (2016), who explore the synergies and trade-offs between FI and stability. They argue that while FI enhances access to services, it does not necessarily lead to their optimal use, and the resultant credit expansion can introduce new risks if not managed appropriately. This perspective challenges the notion that FI should be pursued in isolation, instead advocating for a more integrated approach that considers the full spectrum of financial services and their impacts on both individuals and institutions.\n\nThe empirical literature on FI and financial stability offers a rich diverse of findings, suggesting that a recurring theme across both streams of research is the need to avoid viewing FI or stability in a silo. This concise review of the literature is crucial for our empirical analysis. Prior research seems to have predominantly overlooked the impact of FI on stability, particularly in the context of the Ethiopian banking sector. This study employs bank-level data to offer appropriately tailored policy implication aimed at enhancing bank stability and FI in Ethiopia.\n\n\n3. Methods\n\nCommercial banking institutions in Ethiopia are the most dominant and primary point of access to essential financial services. Based on the data compiled from NBE financial stability report (2024), commercial banks hold for 91.2% of total assets, 97.8% of deposits, 93.9% of credit, and 76.1% of equity in the financial sector, as of June 30, 2023. In light of this dominance, the study focuses on commercial banks but due to data availability concern and the newness of other banks, the researchers focuses on 17 commercial banks. Data for the study sourced from various reliable institutions, like National Bank of Ethiopia (NBE), Commercial banks (CBs) annual report, and World Bank (WB) covering the period 2015-2023.\n\n3.2.1 Dependent variables\n\nIn this research, Z-score is used as a measure of bank stability, following established literature (e.g., Damrah et al., 2023; Koudalo & Toure, 2023; Barik & Pradhan, 2021; Sethy & Goyari, 2022; Vo et al., 2020; Ahamed & Mallick, 2019). Z-score is valued for its ability to indicate bank insolvency risk, reflecting the likelihood that a bank's assets may not cover its liabilities (Koudalo & Toure, 2023). Higher returns on assets and greater capitalization improve stability, while lower figures suggest increased risk (Damrah et al., 2023). This score, calculated from return on assets, volatility, and leverage (Damrah et al., 2023; Vo et al., 2020), is constructed in this study as follows:\n\nWhere: ROA represents the return on assets, EQA denotes the ratio between bank’s total equity and total assets and Sd stands with standard deviation.\n\n3.2.2 Independent variables\n\nMeasuring FI is essential to support evidence-based policy decisions (Sarma, 2016; Nguyen, 2021). Accurate measurement reveals gaps and opportunities for expanding FI (Demirgüç-Kunt et al., 2020). However, relying on a single factor can be misleading (Sarma, 2008; Nguyen, 2021). Composite indices offer a more comprehensive view by integrating multiple dimensions, enabling better comparisons across time and regions (OECD, 2008). These indices capture the multifaceted nature of FI (Mishra, 2007). This study constructs a multidimensional FI index using two-stage PCA, combining10 convensional indicators and 5 digital indicators (see Table 1).\n\n3.2.3 Control variables\n\nAs outlined in Table 1, the study includes several bank-specific and macroeconomic control variables, including an index for operational efficiency. Non-parametric index is used to drive efficiency using an output-oriented Constant Returns to Scale (CRS) through Data Envelopment Analysis (DEA). The choice of CRS is justified by the structure of the Ethiopian banking industry. Ayalew & Xianzhi (2017) highlight that Ethiopian banks operate within a homogeneous regulatory framework with limited competition. Most banks in Ethiopia are subject to similar capital requirements, operational constraints, and government policies, which result in a uniform relationship between inputs and outputs across banks. Despite Rao & Lakew (2012) suggesting that managers in Ethiopian banks have more control over inputs than outputs, most banks prioritize maximizing profits through efficient use of inputs. Thus, assuming out-put oriented CRS provides a realistic framework for comparing efficiency, as banks are expected to scale their operations proportionally regardless of size, making it suitable for long-term efficiency assessments.\n\nIn this study, salary and benefits, provisions, general expenses, branches, and deposits are treated as inputs, while net interest income and non-interest income serve as outputs. Using the model by Charnes et al. (1978) under CRS, the efficiency score θ is calculated as the ratio of weighted sum of outputs to inputs.\n\nWhere (θ) = efficiency score of bank j , Yrj = amount of output r produced by bank j , Xij = amount of input i used by bank j , ur = weight assigned to output r , vi = weight assigned to input i , s = number of outputs, m = number of inputs, n = number of banks (decision-making units) being evaluated.\n\nAdditionally, the analysis includes control variables such as income diversification, capital adequacy ratio, provisions to non-performing loans, loan-to-deposit ratio, and total assets. Macroeconomic variables include the real lending interest rate and GDP growth rate.\n\nPCA is employed to construct an index that effectively reduces data dimensionality while preserving much information (Tram et al., 2023; Nguyen, 2021; Hair et al., 2019; Sha’ban et al., 2020; Camara & Tuesta, 2017). Despite non-parametric approaches like Sarma (2008) model, which often rely assiging weightson researcher’s experience (Tram et al., 2023; Camara & Tuesta, 2017), PCA adapts to changes in data structure (Decancq & Lugo, 2013), avoiding the pre-assignment of weights before data collection (Chen et al., 2019). Additionally, compared to parametric methods like Confirmatory Factor Analysis (CFA), PCA enhances objectivity by not requiring subjective decisions on factor structure (Tram et al., 2023; Camara & Tuesta, 2017; Ismael & Ali, 2021; Jolliffe & Cadima, 2016; Steiger, 1979), which may differ across time and space.\n\nNormalization is essential for comparing indicators with varying units and ranges. Common methods include ranking, z-score standardization, min-max rescaling, and logarithmic transformation (Carrino, 2015; Freudenberg, 2003; OECD, 2008). In this study, the min-max ( MMY ) approach is used to normalize indicators to a scale of 0 to 1, where 0 represents exclusion and 1 represents inclusion.\n\nWhere Ymin , minimum value, Ymax , maximum value\n\nTraditional single-level multivariate analysis often fails to address nested data structures due to its assumption of independent and identically distributed (i.i.d) observations, potentially missing within groupinformation (Yang et al., 2022). To mitigate this, a multi-level framework is employed, which addresses the hierarchical nature of the data, enhancing analytical precision (Yang et al., 2022; Hox, 2013). Additionally, single-stage PCA may disproportionately weight indicators with unequal variances. By generating sub-indices within each dimension separately before combining them, the multilevel approach provides a more balanced and accurate composite index (Ismael & Ali, 2021; Camara & Tuesta, 2017; Nagar & Basu, 2002).\n\n3.3.1 First-stage analysis\n\nTable 2 shows the results of the first-stage PCA. To ensure the suitability of PCA, the Kaiser–Meyer–Olkin (KMO) measure and Bartlett’s test of sphericity are performed. These tests confirm that the sample size is adequate and the indicators are sufficiently intercorrelated (Ismael & Ali, 2021; Taherdoost et al., 2014). A KMO value of 0.5 or higher and a statistically significant chi-square in Bartlett’s test (1950) indicate that factorization is appropriate (Hair et al., 2019). As reported in Table 2, all components meet these criteria (KMO ≥ 0.5 and p-value < 0.05), supporting the use of PCA for FI index development. Additionally, internal consistency was measured using a reliability test. According to Kline (2015), a Cronbach’s alpha value above 0.6 is acceptable for developing scales. The obtained Cronbach’s alpha of 0.9721, as shown in Table 2, exceeds this threshold, indicating excellent internal consistency and enhancing the reliability of the data.\n\nHair et al. (2019) deem an explained variance (EV) of 60% or higher as acceptable. Table 2 shows that PC1 captures a significant portion of the variance in the availability and usage dimensions (91.1% and 86.8%, respectively), confirming their substantial role in FI index development. For digital inclusion, PC1 explains nearly 99.9% of the variance in availability, indicating its dominance. As well, PC1 explains 69% of the variance in accessibility, highlighting that while both dimensions are important, they contribute differently to the FI index. Based on Table 2 first-stage PCA result, the following result is built for each indicators, The dimensions of “availability”, and “usage” of the Convensional sub-index is;\n\nThe analysis reveals that branch availability has the highest relative weight compared to ATMs and PoS machines in both demographic and geographic contexts, emphasizing the crucial role of physical branches in Ethiopia. This finding supports Kebede et al. (2021) and highlights the continued importance of physical branches due to factors such as lower financial literacy, which necessitates in-person interactions. Within the usage dimension, deposit accounts (0.26) hold the highest weight, followed by the deposit to GDP ratio (0.2563), loan to GDP ratio (0.2491), and debit card penetration (0.2347). This underscores the current focus on deposit mobilization in Ethiopia, which collectively emphasize the sector's drive to encourage savings. The dimensions of “Availability”, and “Accessibility” of the digital sub-index is given as follows:\n\nIn digital availability, agency banking indicators (APD and AAD) have equal weights of 0.5, reflecting their equal importance. For digital accessibility, mobile money wallets have the highest weight (0.3848), followed by mobile banking penetration at 0.3757 and internet banking penetration at 0.2394. This indicates that mobile money is the preferred digital financial access method for the general population, contrasting with internet banking, which is primarily used by elitecustomers. This finding aligns with the observation that Ethiopian banks focus internet banking services on premium clients.\n\n3.3.2 Second-stage analysis\n\nTable 3 confirms that the KMO measure exceeds the recommended threshold of 0.5 (Hair et al., 2019), and Sphericity test is highly significant (p-value < 0.0001). The first principal component accounts for 80.07% of the total variance, indicating that only 19.97% of the variance remains unexplained. This result confirms the adequacy of the PCA extraction, as supported by Hair et al. (2019). Among four components, only one has an eigenvalue greater than 1, which is retained for constructing the FII. The derived FII is expressed as follows:\n\nThis equation indicates that Convensional availability (0.2625) has the highest weight, underscoring the critical role of infrastructure development in enhancing FI. This aligns with findings from Nguyen (2021) and Gharbi and Kammoun (2023), emphasizing the need for robust financial infrastructure alongside efforts in financial literacy and user adoption. Usage (0.2616) is the second most significant dimension, reflecting the importance of account usage in FI. Digital accessibility (0.2505) ranks third, highlighting the increasing impact of digital tools. Agency banking, with the lowest weight (0.2254), suggests that while digital solutions are cost-effective, more targeted interventions are required to address the needs of vulnerable populations, including women, rural residents, and those with lower literacy levels.\n\nTo verify the strength of the researchers used the overall average of FI of the country and measured the correlation between the saving and real lending interest rate and newly developed FI index. The Pearson correlation results presented in Table 4 denotes p-values of 0.0000 and 0.0002, respectively, represents that the findings are significant at 1% level (0.9617 for saving) and (-0.9391 for real lending interest rate). The direction of the correlations aligns with theoretical expectations. Real lending interest rates are negatively correlated with FI, as high rates make loans more expensive and discourage access, particularly for low-income populations (Gharbi & Kammoun, 2023; Uddin et al., 2017). Conversely, in relation to deposits, a positive higher FI scores are associated with in-creased savings, likely due to a greater number of households having access to financial institutions and associated saving products (Gharbi & Kammoun, 2023). These robust correlations provide strong evidence for the construct validity of the newly developed FI index.\n\nThis study adopts an empirical exploration, employing a panel methodology, to delve into the crossectional and longitudinal dynamics of evaluating the impact of FI on bank stability —within the period 2015-2023. The empirical model for examining the impact of FI on bank stability, the researchers estimated this dynamic panel model:\n\nWhere, ZSit is the measure of bank stability, represented by Z-score, IFIit , the index of FI extracted from two staged PCA, LDRit , represents the loan to deposit ratio, PLit , refers to provision to loan ratio, lnTAit , indicates the natural logarithm of total asset, CARit , denotes risk weighted capital adequacy ratio, EFit , refers to the efficiency ratio extracted from DEA approach, INDit , refers to non interest income to total income ratio, RLIRit , represents inflation adjusted lending interest rate, GDPit , refers to the gross domestic product growth rate, εit , refers error term, β0 , refers to the constant term,and β1to9 , represents the slope of the independent variables. i = 1.. N & t = 1.. T, denotes to cross-section & time, respectivelly.\n\n\n4. Results and Discusion\n\n4.1.1 Descptive analysis\n\nTable 5 presents the descriptive summary for the variables used to examine the impact of financial FI on bank stability. The analysis is based on a sample of 153 observations, covering 8 years (2015-2023) across 17 commercial banks (all (17) commercial banks operationalized since 2015 are taken for further analysis). The table provides key details, including the mean, standard deviation, and the minimum and maximum values for each variable.\n\n4.1.2 Empirical analysis technique\n\n4.1.2.1 Analysis of ordinary least-square regression (OLS)\n\nUsing fixed or random effects models in OLS regression is common for addressing unobserved heterogeneity and simultaneous causality in panel data (Kumar et al., 2022). Fixed effects handle time-invariant characteristics within firms (Schultz et al., 2010), while random effects reduce variability by pooling data and accounting for differences across firms and time (Kumar et al., 2022). The Hausman test, which checks for the correlation between unique errors and regressors, guides the choice between these models (Kumar et al., 2022; Greene, 2003). Our results indicate that the fixed-effects model is the correct choice, as shown in Table 9.\n\nTo test for autocorrelation and heteroskedasticity, the Wooldridge, modified Wald, and Breusch-Pagan (BP) tests were employed. Results in Table 6 reveals, both problems were detected. However, the correlation matrix and Variance Inflation Factor (VIF) results in Table 7, with all VIF values lessthan 10, suggest that multicollinearity is not a concern. Following Vo et al. (2020) and Ahamed and Mallick (2019), robust clustered standard errors were applied to address these issues, as outlined in Table 9.\n\n4.1.3 GMM analysis\n\n4.1.3.1 Stationary test\n\nConducting a unit root test is crucial to confirm stationarity of variables, thereby avoiding the risk of spurious findings (Breitung & Pesaran, 2005). Although a dynamic panel approach is typically suited for variables integrated at level or first difference, it is crucial to ensure none of the variables is integrated at a higher order, such as I(2) (Pesaran & Smith, 1995). To verify stationarity, we employed the Levin-Lin-Chu (LLC) and Harris-Tzavalis (HT) unit root tests across both I(0) and I(1) levels, as shown in Table 8. The LLC test confirms that all variables, are stationary at level. Similarly, the HT test shows that only total assets achieve stationarity at first difference. Since all variables are either stationary at level or first difference, applying the GMM method is appropriately validated.\n\n* p < 0.05.\n\n** p < 0.01.\n\n*** p < 0.001.\n\nTraditional FE and RE models, while valuable, often struggle to address endogeneity concerns stemming from omitted variables, measurement errors, reverse causality, and time-invariant unobserved heterogeneity in panel data (Hill et al., 2020; Leszczensky & Wolbring, 2022). These issues are exacerbated by the presence of lagged dependent variables and endogenous regressors, leading to biased and inconsistent estimates (Leszczensky & Wolbring, 2022; Bellemare et al., 2017). In the context of dynamic panel data, particularly “small T, large N” panels, selecting an appropriate estimation technique is critical for obtaining reliable and efficient results (Roodman, 2009)\n\nThe Arellano and Bond (1991) estimator is particularly effective in addressing dynamic dependent variables and non-strictly exogenous regressors. By differencing the regressors to eliminate fixed effects and applying GMM, it mitigates potential biases (Roodman, 2009). The system GMM estimator, introduced by Arellano & Bover (1995) and Blundell & Bond (1998), extends this by assuming the first differences of the instruments are uncorrelated with fixed effects, thus incorporating additional instruments and improving estimation efficiency (Jima & Makoni, 2023; Bun & Windmeijer, 2010). System GMM constructs a two-equation system, original levels and transformed differences, leveraging both levels and differences of the instruments (Roodman, 2009). This approach effectively addresses dynamic panel bias, which often distorts small-sample properties and yields unstable estimates when varied instrument sets are employed (Blundell & Bond, 2023; Windmeijer, 2005).\n\nAs noted by Morgan and Pontines (2017), system GMM not only addresses endogeneity bias but also remains consistent and efficient in the presence of heteroskedasticity and autocorrelation within individuals. Our results, as presented in Table 6, confirm the existence of heteroskedasticity and autocorrelation within the model. The system GMM approach is particularly effective in addressing serial correlation and unobserved heterogeneity (Vo et al., 2020; Roodman, 2009). Therefore, employing GMM to overcome these issues aligns with previous empirical studies (Jima & Makoni, 2023; Vo et al., 2020; Ahamed & Mallick, 2019; Morgan & Pontines, 2017).\n\nBlundell et al. (2001) and Bond et al. (2001) highlight significant improvements when dealing with models that include a lagged dependent variable along with other explanatory variables. To tha end, this study refines the previous model into a dynamic form, ensuring more robust and consistent estimations. The specified System-GMM model is as follows:\n\nIn this equation, ZSit represents the dependent variable, αi is the individual-specific effect, φ is the coefficient for the lagged dependent variable, βit are the coefficients for the explanatory variables Xit , and ∈it is the error term.\n\nAs per the works established by Bond et al. (2001), Bond (2002), and Presbitero (2006, 2008), the System GMM estimator was selected based on a comparative analysis of autoregressive( φ ) coefficients derived from Pooled OLS, Fixed Effects, and Difference GMM estimations. Following Bond et al.'s (2001) recommendation, the Pooled OLS coefficient served as an upper bound, while the Fixed Effects coefficient acted as a lower bound. Given that the Difference GMM coefficients (0.347 and 0.328) were significantly lower than the Fixed Effects coefficient (0.412) and well below the Pooled OLS coefficient (0.947), as presented in Table 9, the System GMM approach was deemed appropriate.\n\n* p< 0.1.\n\n** p< 0.05.\n\n*** p< 0.01.\n\nThe System GMM estimator enhances robustness and efficiency by using both difference and level moment conditions to address endogeneity and ensure reliable inference (Sebki, 2021; Soto, 2009; Presbitero, 2008). To handle heteroscedasticity and serial correlation, a two-step System GMM procedure with a consistent weighting matrix from one-step residuals was used (Davidson & MacKinnon, 2004). Although two-step GMM estimates can have downward-biased standard errors (Presbitero, 2008), the small-sample correction by Windmeijer (2005) was applied to improve efficiency, making it preferable over one-step robust GMM (Roodman, 2006). Consequently, the two-step robust System GMM estimator was thus selected for further analysis. To prevent overfitting, the maximum number of instrument lags was constrained. The AR(2) and Hansen tests were conducted to validate the absence of misspecification and the appropriateness of the instrumental variables in the GMM estimation.\n\n4.1.4 Causality test\n\nThis research examines the dynamic causal relationship between FI and bank stability within the Ethiopian banking sector. Both the Dumitrescu and Hurlin (2012) W-statistic test and the Juodis et al. (2021) Z-bar test are used to ascertain the direction of causality between FI and bank stability. Rejection of the null hypothesis indicates a causal relationship, whereas its acceptance suggests none (Antwi et al., 2024). The analysis employs a first lag, with lag selection based on the Modified Bayesian Information Criterion (MBIC) to ensure result robustness, in line with Hussain et al. (2024) and Žiković et al. (2020) recommendations for shorter time periods.\n\nThe findings reveal that the lagged value of bank stability positively effect current stability. Specifically, past levels of bank stability significantly impact present stability, as corroborated by the study of Yitayaw et al. (2023) within the Ethiopian context. The positive effect of lagged stability on current conditions underscores its validity as a reliable instrument for stability analysis, given that banks generally exhibit continuity in their stability across different periods, reflecting a trend of persistence over time.\n\nOur findings confirm a significant positive relationship between FI and bank stability, supported by existing research (Koudalo & Toure, 2023; Nguyen & Du, 2022; Vo et al., 2020; Le et al., 2019; Neaime & Gaysset, 2018; Morgan & Pontines, 2014). Specifically, a 1% increase in FI is associated with an 84.07 unit increase in bank stability in the short run, ceteris paribus. Enhanced FI strengthens bank stability by diversifying bank assets, reducing systemic and liquidity risks, and improving monetary policy transmission (Ahamed & Mallick, 2019; Morgan & Pontines, 2014; Khan, 2011; Hannig & Jansen, 2010). It also addresses information asymmetry by allowing lenders to better assess borrowers and by providing banks with critical proprietary information (Nguyen & Du, 2022), thus fostering a more resilient banking sector.\n\nOur findings indicate that control variables such as lnTA, EF, IND, and GDP growth rate significantly affect bank stability. Larger banks exhibit decreased stability, with a 10.03 unit decline per percentage increase in total assets in the short run, ceteris paribus. This may be due to increased operational and systemic risks associated with larger institutions, aligning with Vo et al. (2020) and Mu and Lin (2016), but differing from Nguyen and Du (2022) and Ahamed and Mallick (2019). Efficiency positively effect stability, with a 1% increase in efficiency leading to a 26.24 unit rise in stability in the short run, ceteris paribus. This suggests that higher efficiency improves profitability and stability, consistent with Nguyen and Du (2022), and Ahamed and Mallick (2019). Income diversification negatively impacts stability, with a 1% increase resulting in a 101.7 unit decrease in stability in the short run, ceteris paribus. This might reflect the risks introduced by diversification, aligning with Nguyen and Du (2022) but differing from Ahamed and Mallick (2019). In the Ethiopian context, where banks are predominantly dependent on deposit revenue, an abrupt or poorly managed shift towards greater non-interest income might contribute to instability. GDP growth rate shows a positive effect on stability, with a 1% increase leading to a 229.5 unit rise in stability in the short run, ceteris paribus. This suggests that economic growth enhances bank stability, consistent with Nguyen and Du (2022), Vo et al. (2020), and Ahamed and Mallick (2019).\n\nThe two-step System GMM analysis, as detailed in Table 9, shows that the standard diagnostic tests are supportive of the model’s validity. The AR(2) test (Prob > χ2 = 0.479) does not reject the null hypothesis, indicating no evidence of second-order residual autocorrelation. Similarly, the Hansen test (Prob > χ2 = 0.951) confirms the validity of the instruments, verifying their appropriateness. The F-test (Prob > F = 0.000) demonstrates a strong goodness of fit for the model. In addition to the two-step robust System GMM results, findings from robust FE, robust Pooled OLS, robust one-step Difference GMM, robust two-step Difference GMM, and robust one-step System GMM are largely consistent. The main variable, FI, is significant in both one-step and two-step System GMM models, while the GDP growth rate is significant in the two-step robust System GMM. Overall, these results underscore the robustness of the employed models.\n\nIn addition, based on the result revealed in Table 10, the Juodis et al. (2021) test confirms that FI significantly Granger-causes bank stability at the 5% level, a result supported by the Dumitrescu and Hurlin (2012) test, which also rejects the null hypothesis. This underscores the substantial role of FI in bolstering the resilience and stability of Ethiopia's banking sector. Additionally, reverse causality from bank stability to FI is significant at the 5% level, indicating that bank stability can predict enhancements in FI. These findings suggest that enhancing FI can improve bank stability, while a stable financial environment fosters greater FI, aligning with previous studies (Jima & Makoni, 2023; Antwi et al., 2024).\n\n* p< 0.1.\n\n** p< 0.05.\n\n*** p< 0.01.\n\n4.2.1 Limitations and future research directions\n\nThis study acknowledges the following limitations. First, it does not account for regional disparities within Ethiopia, which may be shaped by the diverse economic and social landscapes across the country’s regions. Future investigations should prioritize a more detailed analysis that incorporates regional policy perspectives, as this would yield richer insights and support the creation of customized interventions aimed at promoting FI both at the regional and national levels. Secondly, although there were attempts to include digital financial indicators, the lack of transaction data from pertinent authorities hindered the incorporation of these variables into the construction of the index. Consequently, future studies should address this gap. Lastly, upcoming research could gain from the application of alternative data-driven methodologies, such as CFA.\n\n\n5. Conclusion and policy implication\n\nFinancial inclusiveness has increasingly become a focal point for policymakers, practitioners, and economists due to its potential to drive inclusive growth. Despite numerous efforts by policy makers and international financial institutions to bolster bank stability and inclusivity, the relationship between FI and bank stability remains contentious and inconsistent in existing literature. This study addresses this gap by examining the impact of FI on bank stability within the Ethiopian context. Using panel data from seventeen commercial banks over the period 2015-2023, the researchers employed a two-stage PCA to develop FI index based on ten Convensional and five digital indicators. The effects of FI on bank stability were analyzed using a two-step robust System GMM approach, complemented by Granger causality tests to determine the direction of causality between FI and bank stability.\n\nOur results from the two-stage PCA indicate that Convensional availability is the most important factor in FI score, followed by Convensional usage, with digital accessibility and digital availability ranking third and fourth, respectively. The System GMM analysis confirms that FI has a significant and positive effect on bank stability. Control variables such as efficiency and GDP growth rate are positively associated with bank stability, while total assets and income diversification exhibit negative effects. Additionally, the historical level of bank stability positively effects current stability. The Granger causality tests indicate a bi-directional relationship between FI and bank stability, suggesting that improvements in FI contribute to enhanced stability, and vice versa.\n\nThe policy implications are profound. To promote both FI and stability, policymakers should focus on expanding demographic and geographic outreach, enhancing both convensional and digital financial services. Ensuring that current stability supports future stability is also crucial. FI and bank stability are mutually reinforcing; efforts to enhance FI directly contribute to improved stability and vice versa. Consistent with the policy implication of Vo et al. (2020), broadening FI is essential for strengthening banking sector stability in Ethiopia. Expanding financial services to underserved populations not only provides banks with stable funding sources but also enhances overall sector stability and profitability. Additionally, echoing Oanh et al. (2023) implications, governments should address financial exclusion by removing barriers to access, improving financial education, and developing infrastructure in underserved areas. Policymakers must also ensure that initiatives to promote FI are supported by appropriate macroeconomic policies to sustain the positive relationship between FI and bank stability.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nFigshare: Dataset for financial inclusion and stability in Ethiopia case, https://doi.org/10.6084/m9.figshare.27327804.v2 (Arebo et al., 2024).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nNot applicable.\n\n\nReferences\n\nAbdu E: Financial distress situation of financial sectors in Ethiopia: A review paper. Cogent Econ. Financ. 2021; 10: 1–13. Publisher Full Text\n\nAdem M: Impact of diversification on bank stability: evidence from emerging and developing countries. Discret. Dyn. Nat. Soc. 2022; 2022(1): 7200725. Publisher Full Text\n\nAhamed MM, Mallick SK: Is financial inclusion good for bank stability? International evidence. J. Econ. Behav. Organ. 2019; 157: 403–427. Publisher Full Text\n\nAkerlof GA: The market for lemons: Quality uncertainty and the market mechanism. Q. J. Econ. 1970; 84(3): 488–500. 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}
|
[
{
"id": "354020",
"date": "22 Jan 2025",
"name": "Najabat Ali",
"expertise": [
"Reviewer Expertise FDI",
"Technology Innovation",
"Green Tarde",
"Green Innovation",
"Sustainable Economic Development",
"Environmental Sustainability"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThanks for inviting me to review the current manuscript. The manuscript has some merits, but its current quality does not meet the indexing standard. Therefore, before indexing, the manuscript needs the following significant modifications:\n1. The authors must add a specific policy recommendation in the abstract section. 2. The study's novelty should be highlighted by comparing the current study with previous studies in the field. 3. The theoretical framework should be added. 4. The literature review section should be enriched with the most recent studies. 5. In the methodology section, justify the methods used in your study by comparing them with the existing field methods. 6. The graphical presentation of the methodology will be easier for the authors to understand. 7. In the results and discussion section, compare your results with the existing field studies. 8 The conclusion, policy implications, and limitations should be written under separate headings. 9. An English language check is required to avoid grammatical and spelling errors.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "13214",
"date": "27 Jan 2025",
"name": "Mohammed Arebo",
"role": "Author Response",
"response": "Dear Professor Najabat Ali, We sincerely thank you for the time and effort you have dedicated to reviewing our work, particularly for your prompt review report. Your insightful comments will undoubtedly enhance the quality of our manuscript. We eagerly anticipate additional feedback and suggestions from the other reviewers, and upon receipt, we will take your nine comments into account in the revised version of this article. Regards Mohammed Jatoro Arebo Main and corresponding author"
}
]
}
] | 1
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https://f1000research.com/articles/13-1369
|
https://f1000research.com/articles/13-1368/v1
|
15 Nov 24
|
{
"type": "Systematic Review",
"title": "Performance of Forensic Age Estimation by Aspartic Acid Racemization and DNA Methylation: A Systematic Review",
"authors": [
"Eko Prastyo",
"Elza Ibrahim Auerkari",
"Antonius Winoto Suhartono",
"Roben Suhadi Pasaribu",
"Achmad Gigih Andy Putra",
"Pertti Auerkari",
"Eko Prastyo",
"Antonius Winoto Suhartono",
"Roben Suhadi Pasaribu",
"Achmad Gigih Andy Putra"
],
"abstract": "Background Forensic age estimation is not difficult when the body is found in good condition, but in cases of severe decomposition or damage, such as burnt or separated body parts, then the analysis can only be done with bones and teeth. There has been abundant research and development in the field of related biochemistry over the years. Various molecular changes occur in hard tissues and long-lived proteins, such as those in bones and teeth during the physiological process of aging. Aspartic acid racemization and DNA methylation are still the most frequently used age estimation methods because of their advantages in accuracy.\n\nMethod This study aimed to compare the accuracy of DNA methylation and aspartic acid racemization methods for age estimation. Journal articles were searched in the electronic databases PubMed, Scopus, and Semantic Scholar of 2017-2022 according to PRISMA guidelines.\n\nResult Twelve journal articles were eligible for review. The DNA methylation method is quite simple to use because of commercially available methylation kits. Furthermore, the results can be obtained relatively quickly without requiring many samples, and the method is less sensitive to thermal and other damage than the aspartic acid racemization method.\n\nConclusion The aspartic acid racemization method for age estimation has high accuracy, especially in determining age at death. However, temperature and the condition of the teeth affect the racemization of aspartic acid. Given that DNA methylation is generally stable in a wide range of temperatures, it provides a better approach to determining the chronological age even from charred remains.",
"keywords": [
"Age estimation",
"aspartic acid racemization",
"DNA methylation",
"forensics"
],
"content": "Background\n\nForensic age estimation is not particularly challenging when the body is found in decent condition. However, when the body is severely decomposed or damaged, such as consisting of separated or burnt body parts, age estimation can only be done by using features and material samples of bones and teeth.1,2 Several methods are used to estimate age, such as the closure of the cranial sutures, changes in the ends of the sternal bones, and morphological changes in the symphysis pubis and the surface of the auricular. However, the skill and experience of the person analyzing the body determine the accuracy of these traditional methods, and they have a wide range of estimation errors, from 10 to 20 years.3\n\nDevelopmental methods such as the dimensions of the bones, the presence of ossification centers, the fusion of the epiphyses, the mineralization of the teeth, and the eruption of the teeth can be used to estimate age very accurately in childhood. After childhood, the transitional stage is distinguished by the cessation of bone growth and development (between the ages of 20 and 25). There are also several age-related characteristics, such as the fusion of the sternoclavicular, iliac crest epiphyses, loss of fronto-sphenoid sutures and spheno-occipital or basilar synchondrosis, and the development of third molars. For adults, several morphological methods use teeth, symphysis pubis, fourth rib, auricular surface, and acetabulum to assess age.4\n\nProtocols for age estimation using morphological methods are currently being withdrawn because the results obtained are inaccurate and provide a margin of error of greater than ten years. Therefore, over time biochemical methods have received increasing and wider attention for development.5 Age estimation can be conducted by using several molecular biomarkers, including aspartic acid racemization, DNA damage response, DNA methylation, T-cell DNA rearrangement, mitochondrial DNA mutations, advanced glycation end products (AGEs), and telomere shortening.6,7 Physiological aging involves molecular changes in long-lived proteins and hard tissues including teeth and bones. Of such methods, aspartic acid racemization and DNA methylation are still most frequently used for age estimation because of their advantages in terms of accuracy.3\n\n\nMethods\n\nThis research followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).8 (https://doi.org/10.5281/zenodo.13624062).\n\nThe approach of PICO (Population-Interventions-Control-Outcomes) was used to define the eligibility criteria. The following criteria were used: P: people of all age groups and genders; I: aspartic acid racemization method; C: DNA methylation method and O: age estimation.\n\nExclusion criteria were as follows: (1) Text is not original research (case reports, narrative reviews, controlled clinical trials, or case series), (2) experiments involving experimental animals, (3) texts not available in full, and (4) texts written in a language other than English.\n\nSystematic electronic literature searches were performed in Scopus, MEDLINE/PubMed, and Semantic Scholar databases for literature published in 2017-2022. The last electronic search was performed on 28 December 2022. The literature search strategies are shown in Table S 1 (Refer extended data).\n\nE.P. conducted an initial literature evaluation and selection. Subsequently, the articles were evaluated and approved by R.S.P and A.G.A.P. The article selection process consisted of reducing duplicates, after which the articles were screened for the above-mentioned keywords in their titles and abstracts. The second screening was conducted according to the inclusion and exclusion criteria to find relevant full texts, and we selected articles that met the requirements. Then, the full texts were reviewed (read and graded) by all three reviewers to retrieve relevant data. Discussion and consensus were used to resolve disagreements between reviewers.\n\nThree reviewers synthesized data independently to avoid bias when conducting reviews. The data synthesized included the name of the first author of the journal, year of publication, source and the number of samples, research location, method, treatment of aspartic acid racemization (preparation and laboratory techniques), and treatment of DNA methylation (DNA extraction technique, bisulfide treatment, and target genes), examination techniques, research results, conclusions, and research limitations.\n\nTo ensure quality and minimize the risk of bias, the authors conducted a study evaluation based on a scoring tool that assesses the quality of a systematic review study.9 This checklist consists of 11 components and can aid inclusion in Systematic Review studies.9\n\n\nResults\n\nSearches were performed on three electronic databases: PubMed/MEDLINE (n = 154), Scopus (n = 255), and Semantic Scholar (n = 19) using the BOOLEAN system to find a total of 428 journal articles. Out of 428 articles, 299 were automatically excluded by the system for being published before 2017 and 53 were excluded as they were duplicates, bringing the total number of articles to 76. Automatic filtering was performed to exclude 32 articles that were not research articles, bringing the total to 44 articles. With title and abstract screening to find articles that match the inclusion criteria, 23 articles were excluded, bringing the total number to 21. Twenty-one articles were read in full, and 9 did not meet the criteria or did not answer the PICO. The final number of articles to be reviewed was 12. The flowchart of this study is explained in Figure S1 (Refer extended data) below.\n\nThe results of the literature synthesis include the first author, year of publication, sample source, number of samples, population, method, treatment (DNA extraction technique, bisulfide treatment, preparation stage, and laboratory stage), examination technique, results, conclusions, and research limitations (Table S 2). Refer extended data.\n\nOf the 12 journal articles, research was conducted in several countries such as Japan (n = 2), China (n = 1), Germany (n = 1), Poland (n = 1), Austria (n = 1), Spain (n = 3), Scandinavia (n = 1), Pakistan (n = 1), and Kuwait (n = 1). Eleven articles used teeth as a sample source to be tested and 1 study used blood as a sample source.\n\n\nDiscussion\n\nAspartic acid racemization has the primary benefit of using samples collected from tissue (dental) that have been shielded from numerous environmental and nutritional variables, giving a margin of error of approximately 1.5-4 years.10–12 The majority of organisms only have the L-form (levo) of optically active amino acids initially, which is then partially converted to the D-form (dextro) until equilibrium is attained over time or with aging, resulting in a mixture of the two forms called a racemic mixture.\n\nThe D/L ratio of aspartic acid is 1.0 in this equilibrium. This spontaneous conversion process is called racemization and causes a conformational change of a metabolically stable protein, thus driving a change in its activity and biochemical properties. This conversion stops at death (except when the body is placed in a hot environment), as the racemization rate relies on temperature, pH, and humidity, both in vivo and postmortem.10,12–16\n\nRacemization occurs in long-lived proteins. Aspartic acid has the fastest racemization rate, followed by alanine, glutamic acid, isoleucine, and leucine. Thus, age estimation methods use aspartic acid most often.10,16,17 Modifications due to the instability of aspartate and asparaginyl residues in proteins may increase D-aspartate residues with age. Amino acids continuously undergo formation and degradation. In such cases, proteins with high metabolic rates provide less accurate results than tissues with low metabolic rates and long-lived proteins.10\n\nIn humans, long-lived proteins with low metabolic rates can be found in the hard tissues of teeth, bones (type I collagen, osteocalcin, telopeptide), eye sclera (elastin), arterial walls (elastin), lung parenchyma (elastin), intervertebral discs, articular cartilage (proteoglycan), brain (tubulin, proteoglycan, synapsin, myelin basic protein, β-amyloid protein, white matter, tar protein), cartilage, ocular lens (αA-crystallin), erythrocyte membrane protein, epiglottis, and skin. Hard tissues, such as teeth and bones, remain well preserved after all soft tissues have deteriorated. Teeth are often well preserved even when large portions of bone have been mutilated or destroyed.10,12 The use of non-dental tissues such as cartilage, elastin, or bone in the aspartic acid racemization\n\nSeveral studies have analyzed various dental tissues such as enamel, dentin, cementum, or using the teeth. Dentin is the best tissue for age estimation and these results have been demonstrated in many populations.18 Age and the degree of aspartic acid racemization in root dentin are strongly correlated (0.96-0.98). Root dentin is considered to provide fairly accurate results because it is considered less affected by disease (e.g., caries), repair processes (e.g., presence of reparative dentin), or restoration. Dentin also has a greater proportion than enamel and is subject to fewer changes, such as attrition. The presence of caries on teeth will affect the level of racemization as caries will induce protein degradation, causing faster accumulation of D-aspartic acid. Therefore, the degree of racemization will be very high in samples taken from carious teeth, even if the sample comes from an area that is not affected by caries. Thus, it is not recommended to use carious tooth samples. Tooth samples that have been deposited for a long time may have smaller peptide fragments, leading to a more rapid conversion of the L-form to the D-form resulting in the higher accumulation of D-Asp. Ultimately, such protein degradation can produce high false-age estimates of death.3,10,12,14,19,20\n\nGenerally, aspartic acid racemization is quite complex, involving extracting the dentin from the tooth, powdering the dentin, and extracting the amino acids. Therefore, samples are analyzed by gas chromatography (GC), which is considered the most sensitive method.21 The teeth’s position and the time required for dentine formation also affect the racemization rate. High-power liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are widely used for analysis.10 HPLC is considered an easier method for separating aspartic acid when compared to the GC method. Research conducted using the HPLC method shows that it can be effectively used to calculate chronological age by aspartic acid racemization. It can also deliver reliable results and only requires a short analysis time.5,14 However, the GC method is considered the most sensitive method. GC allows determining the quantitative ratio between the two isomers of the D-form and the L-form, which is then used in calculations.10,13\n\nSeveral studies have compared the two techniques of GC and HPLC and observed the resulting advantages, stating that the HPLC technique is better for age estimation. However, other studies have provided better results through the GC technique. Therefore, neither of these techniques (HPLC or GC) is likely to be strictly more favorable than the other.18 Expressing the racemization ratio as ln [(1 + D/L)/(1–D/L)] and placing this logarithmic racemization ratio on the y-axis and chronological age on the x-axis, a linear regression equation is obtained as\n\nDifferences in environment, climate, genetics, race, nutrition, type of teeth used, part of the teeth used, temperature, humidity, and pH can cause different levels of racemization in each population. Temperature also has a huge effect on the D/L ratio. Moreover, the rate of aspartic acid racemization in tissues will increase with high temperatures; teeth that are located deeper in the oral cavity will also have a higher rate of racemization, because of the higher surrounding temperature. Previous studies have also shown that the older the sample, the greater the error. Age determination will be more accurate if it is done on samples younger than 35 years.3,14\n\nIt is also advisable to choose the incisors or premolars because both teeth are small, single-rooted, and easy to obtain enough dentin (overall) compared to molars with multiple roots. In tooth development, dentin is formed over years from the crown to the root apex concentric cones. In young people, the dentin D/L ratio is predicted to be larger in the crown than in the root. However, in elderly people, the opposite is true.11,14 However, there are also studies using third molars, arguing that these teeth are the last teeth to mineralize and grow, indicating that they were obtained from samples that were at least 18 years old. Moreover, they are less prone to caries and their position in the mouth protects them from environmental factors, making them ideal for research samples.16\n\nWhen compared with the DNA methylation method, aspartic acid racemization can still be used for archaeological sample analyses because the protein can be preserved well over a lengthy period while extracting sufficient intact DNA for DNA methylation analysis is very difficult.19,22\n\nAspartic acid racemization using bone samples is strongly influenced by the sex of the sample. Men’s bones are less affected by bone disease than women’s bones. Women’s bones are more affected by bone disease after menopause as the lack of estrogen leads to bone resorption and increased osteoclast activity. Consequently, typically the D/L ratio in female bones does not correlate with chronological age, especially after menopause.3\n\nThe aspartic acid racemization method’s sensitivity to temperature is one of its drawbacks. Thus, it cannot be used for burnt samples or bodies that have been exposed to high temperatures. In addition, this is an invasive method that cannot be applied to individuals who are still alive. This method also often requires expensive instruments.12,17 Moreover, this method damages the sample, so care is needed when analyzing the samples that are available in limited quantities.23 Age-related conditions brought on by protein aggregation, such as Alzheimer’s disease, cataracts, and arteriosclerosis, have also been linked to aspartic acid racemization reactions.21\n\nThe process of altering the number 5’ carbon atom in a cytosine residue followed by a guanine residue is known as DNA methylation. Thus, it is known as a CpG(s)/CpG sites dinucleotide. Only at position 5 of the CpG dinucleotide sequence, in the pyrimidine ring of cytosine, is the replication process in DNA methylation found. The most accurate epigenetic alteration technique for determining the age of human biological samples is DNA methylation. In the genome, methylation (addition of a methyl group) occurs in a CpG-rich region (at the cytosine nucleotides in the cytosine/guanine region) called the CpG island. CpG islands are located on gene regulators such as promoters, intergenic regions, and repeat elements. Methyl-CpG domains and protein binding will bind specifically to the CpG island, and induce transcriptional activation and repression.7,24,25 The level of total DNA methylation will decrease with increasing age of the individual.26 DNA methylation is essential for several biological processes, including cell differentiation, embryonic development, and the regulation of gene expression.27\n\nThe correlation between aging and DNA methylation can be explained in two ways: epigenetic drift and epigenetic clock. While the epigenetic clock is only weakly related to age, epigenetic drift reveals a variety of alterations in individuals related to age due to environmental influences. Therefore, it can be used to predict chronological age. In males and females, the CpG sites have different levels. Methylation on the X chromosome also tends to be more unstable. Women’s susceptibility to certain diseases and stress also greatly influences DNA methylation levels. Thus, many factors affect DNA methylation. Additionally, the metabolic syndromes and degenerative diseases of everyone also influence the percentage of DNA methylation.7\n\nThere are three ways to detect and analyze DNA methylation: utilizing restriction endonuclease digestive enzymes, converting sodium bisulfite, and increasing affinity with methyl-binding proteins or CpG-specific antibodies. The conversion of sodium bisulfite is a common procedure used in the field of forensics for the analysis and detection of DNA methylation. Examples of sodium bisulfite conversion procedures have been used in forensic odontology on teeth, saliva, and buccal swabs. Meanwhile, forensic examinations are generally conducted through blood, sperm, and urine.23 The bisulfite conversion technique currently appears to be the most promising, although it requires a larger number of DNA samples than conventional forensic examinations.28\n\nSeveral markers related to age estimation have been researched for different tissues, including blood, buccal swabs, saliva, sperm, bone, and teeth, enabling these tissues to be used as highly accurate age prediction models (APM).29 Many methodologies are used for sequencing bisulfite targets including pyrosequencing, Sanger sequencing, EpiTyper, massive parallel sequencing or SNaPshot, and methylation-sensitive high-resolution melting (MS-HRM).27,30\n\nInvestigations most commonly use pyrosequencing. The primary advantage of pyrosequencing is the ability to obtain highly accurate quantitative DNA methylation data by the direct sequencing of PCR products. Nevertheless, there are limitations to this method, such as the relatively high cost and pyrosequencer’s low penetration rate.27 Methylation levels can be quickly and relatively cheaply quantified using the PCR-based approach, MS-HRM. This technique compares the melt profiles of unknown PCR products with PCR products obtained from standards with known methylation ratios to determine DNA methylation levels.27\n\nFurthermore, CpG in the FHL2 and ELOVL2 genes has been linked to age estimation in numerous studies along with the markers NPTX2, SCGN, and KLF14. ELOVL2 is a stable epigenetic marker. This locus was used as a marker that correlated strongly with age in many APMs obtained from specific tissues such as blood, teeth, bone, and buccal swabs, providing results with similar high accuracy across all APMs. A transcription co-factor called FHL2 is involved in processes such as cell cycle regulation, wound healing, and bone formation. Gene expression is regulated in adipose tissue by the KLF14 transcription factor. Other studies also mention that several other genes can also be used as markers in age estimation, among them are EDARADD, PDE4C, C1orf132, TRIM59, PENK, TOM1L1, IASPA, TGA2B, CCDC102B, ZBF423, NHLRC1, SCGN, CSNK1D, and MIR29B2C. ELOVL2 and TRIM59 gave better results as multi-tissue markers than FHL2, KLF14, and C1orf132.24,28–31 The other most promising candidate gene is NRCAM, which displayed the strongest age correlation in both the validation and screening datasets (R2 = 0.84 and R2 = 0.46, respectively).28\n\nThe right gene must be chosen to create a model for age estimate that is accurate. As LOVL2’s methylation rate has a strong, positive correlation with age, it has the highest potential for modeling age estimation. Other genes that are positively correlated are PDE4C and FHL2. Meanwhile, EDARADD, ASPA, CCDC102B, C1orf132, and chr16:85395429 methylation rates are negatively correlated with age.27,28 Using DNA methylation levels for age estimation will give better results in samples with a younger age range. Conversely, there will be a reduction in accuracy (increase in MAD value) with age.29\n\nSeveral studies have shown a greater difference between chronological age and estimated age when using all tooth tissue for analysis compared to separating individual layers of the tooth. Differences in composition between layers and differences in cell types can affect the methylation status of selected genes.24 A factor that can affect DNA methylation and must be considered before performing DNA analysis is the presence of some clinical conditions, diseases, or lifestyle habits such as drinking alcohol or smoking, which can interfere with methylation data.29\n\nBlood is utilized for DNA methylation-based age estimates since it is reasonably easy to collect. Teeth are more reliable sources of DNA than blood samples, even in badly decayed bodies (e.g., burnt cadavers, and white skeletons). Of the various types of teeth, molars provide the best protection for DNA. DNA is used for age estimation by analyzing its methylation level.27 DNA in teeth originates from dentin (odontoblasts), dental pulp (immune cells, odontoblasts, fibroblasts, and undifferentiated mesenchymal cells), and cementum (cementocytes). In a study on 21 modern teeth from 7 to 77 years old, analysing methylation levels of ELOVL2, FHL2, and PENK genes, the median difference between chronological age and estimated age was smaller in pulp (2.25 y, SD = 2.5 y) and cementum (2.45 y, SD = 3.3 y) than in dentin (7.07, SD = 7.0).27 Another study of 20 third molars from 22 to 70 years old subjects analysed CpG methylation levels of ELOVL2, KLF14, SCGN, NTPX2, and FHL2 genes from pulp samples, using bisulfite-modified PCR and pyrosequencing.24 Although the methylation status of individual genes and CpG sites provided at best relatively modest (though significant) correlation with age, multivariate models of combined genes with multiple CpG sites improved the correlations considerably and provided age estimates with mean absolute error (MAE) values of only 1.5-2.1 years.24\n\nThe DNA content in premolars and molars is higher than in incisors and canines, this is possible because of the higher cellularity potential results from a relatively larger cementum size and larger pulp volume, more stable alveolar, and more anatomical protection. Thus, molars are more resistant to postmortem loss or contamination. Odontoblasts, as the principal cells in the pulp-dentin complex, degrade rapidly and disappear as soon as 5 days after death. Both cementum and pulp are major sources of dental genomic DNA.32\n\nDNA methylation analysis is now being used to estimate age for forensic identification, taking the place of earlier approaches. This procedure is very straightforward because it makes use of a readily available methylation kit. Additionally, the results can be obtained relatively fast and with a small number of samples. When compared to other DNA analysis methods like telomere shortening and sjTREC, DNA methylation examinations to estimate a person’s age also have the best correlation with chronological age. Currently, research on DNA methylation is still mostly performed with blood samples, but it has also begun to be conducted by taking samples from oral tissues, such as saliva, gingiva with swabs, and teeth.4,23,26,31,33\n\n\nConclusion\n\nThe method of analyzing the racemization of aspartic acid to estimate age has a high degree of accuracy, particularly in determining age at death. However, a limitation of this analysis method is that aspartic acid racemization is influenced by temperature and the condition of the teeth being sampled, such as caries. Given that DNA methylation is generally stable throughout a wide temperature range, it is possible to use this technique to determine the chronological age of even charred remains with satisfactory accuracy.\n\n\nAuthors’ contributions\n\nE.P., E.I.A, R.S.P., and A.G.A.P. conducted to study design and contributed to the initial draft of the manuscript. E.I.A., P. A, and A.W.S. supervised and approved the study. E.P. conducted the literature research and interpretation of data on the two compared methods, with R.S.P. and A.G.AP. as supporting observers. E.I.A., P. A, and A.W.S. contributed by critically revising the manuscript and approving the version for publication. All authors have read and approved the final manuscript.\n\n\nEthics approval and consent to participate\n\nEthical approval and consent were not required.\n\n\nConsent for publication\n\nNot applicable.\n\n\nAuthor details\n\n1Forensic Odontology Specialist Study Program, Department of Oral Biology, Faculty of Dentistry, University of Indonesia, Indonesia.\n\n2Division of Forensic Odontology, Department of Oral Biology, Faculty of Dentistry, University of Indonesia, Jakarta, Indonesia\n\n3Master Programme in Dental Sciences, Division of Forensic Odontology, Faculty of Dentistry, University of Indonesia, Indonesia\n\n4Master’s Programme In Biomedical Sciences, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia\n\n5Department of Mechanical Engineering, School of Engineering, Aalto University, Finland",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: Performance of Forensic Age Estimation by Aspartic Acid Racemization and DNA Methylation: A Systematic Review, DOI: https://doi.org/10.5281/zenodo.13624062.34\n\nThe project contains the following reporting guidelines:\n\n• Prisma Flowchart.jpg\n\n• Checklist for Performance of forensic age estimation by aspartic acid racemization and DNA methylation a systematic review.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nZenodo: Performance of Forensic Age Estimation by Aspartic Acid Racemization and DNA Methylation: A Systematic Review, DOI: https://doi.org/10.5281/zenodo.13624062.34\n\nThe project contains the following extended data:\n\n• Table 1. Electronic literature search strategy.docx\n\n• Table 2. Journal synthesized results.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThe authors thank the Universitas Indonesia for accessing library services.\n\n\nReferences\n\nTamara L, Irena ZP, Ivan J, et al.: ATR-FTIR Spectroscopy as a Pre-screening Technique for the PMI Assessment and DNA Preservation in Human Skeletal Remains – A Review. Quat. Int. 2022; 660(April): 56–64. Publisher Full Text\n\nSinha M, Rao IA: Review Article Genetics and Molecular Biology Techniques Applications in Forensic Dentistry-A Review. Int. J. Multidiscip. Curr Res. J. 2017; 5(April): 315–319.\n\nMonum T, Jaikang C, Sinthubua A, et al.: Age Estimation Using Aspartic Amino Acid Racemization from a Femur. Aust. J. Forensic Sci. 2019; 51(4): 417–425. Publisher Full Text\n\nZapico SC, Stone-Gordon R, Adserias-Garriga J: The Evolution of Methodology in Biochemical Age Estimation. Age Estimation: A Multidisciplinary Approach. Elsevier Inc.; 2019; 189–197.\n\nHassan Q, Rakha A, Zahid BM: Aspartic acid racemization with correlation to age: A forensic perspective. J. Coll. Physicians Surg. Pak. 2017; 27(5): 283–287. PubMed Abstract\n\nShi L, Jiang F, Ouyang F, et al.: DNA Methylation Markers in Combination with Skeletal and Dental Ages to Improve Age Estimation in Children. Forensic Sci. Int. Genet. 2018; 33(August 2017): 1–9. PubMed Abstract | Publisher Full Text\n\nYudianto A, Mieke Sylvia Margaretta AR, Setiawan F, et al.: Human Age Estimation Through DNA Metilation Analysis Method from Bite Mark Samples in Forensic Identification. Indian J. Forensic Med. Toxicol. 2021; 15(1): 706–713.\n\nShamseer L, Moher D, Clarke M, et al.: Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (Prisma-p) 2015: Elaboration and Explanation. BMJ (Online). 2015; 349(January): 1–25. Publisher Full Text\n\nBriggs J: Checklist for Systematic Reviews and Research Syntheses. The Joanna Briggs Institute; 2017; p. 7.\n\nPillalamarri M, Manyam R, Pasupuleti S, et al.: Biochemical Analyses for Dental Age Estimation: A Review. Egypt. J. Forensic Sci. 2022; 12(1). Publisher Full Text\n\nSaputri RI: Estimasi Usia Dental Berdasarkan Pendekatan Biomolekuler. Insisiva Dental Journal: Majalah Kedokteran Gigi Insisiva. 2020; 9(1): 31–38. Publisher Full Text\n\nZapico SC, DeGaglia CM, Adserias-Garriga J: Age estimation based on chemical approaches. Age Estimation: A Multidisciplinary Approach. Elsevier Inc.; 2019; pp. 199–211.\n\nWochna K, Bonikowski R, Śmigielski J, et al.: Aspartic Acid Racemization of Root Dentin Used for Dental Age Estimation in a Polish Population Sample. Forensic Sci. Med. Pathol. 2018; 14(3): 285–294. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElfawal MA, Alqattan SI, Ghallab NA: Racemization of Aspartic Acid in Root Dentin as a Tool for Age Estimation in a Kuwaiti Population. Med. Sci. Law. 2015; 55(1): 22–29. PubMed Abstract | Publisher Full Text\n\nTeglind R, Dawidson I, Balkefors J, et al.: Analysis of 14C, 13C and Aspartic Acid Racemization in Teeth and Bones to Facilitate Identification of Unknown Human Remains: Outcomes of Practical Casework. Biomolecules. 2021; 11(11). PubMed Abstract | Publisher Full Text | Free Full Text\n\nZapico SC, Ubelaker DH: Application of Aspartic Acid Racemization for Age Estimation in a Spanish Sample. Biology (Basel). 2022; 11(6): 1–9.\n\nChakraborty A, Kundu A, Sarkar S, et al.: A Review on Clinical and Forensic Perspective of Dental Age Estimation in Children. Int. J. Eth. Trauma Victimology. 2022; 8(1): 1–5.\n\nMatteussi GT, Jacometti V, Franco A, et al.: Age Estimation in Humans Through the Analysis of Aspartic Acid Racemization from Teeth: A Scoping Review of Methods, Outcomes, and Open Research Questions. Forensic Sci. Int. 2022; 331: 111154. PubMed Abstract | Publisher Full Text\n\nMahlke NS, Renhart S, Talaa D, et al.: Molecular Clocks in Ancient Proteins: Do They Reflect the Age at Death Even After Millennia? Int. J. Legal Med. 2021; 135(4): 1225–1233. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSirin N, Matzenauer C, Reckert A, et al.: Age estimation based on aspartic acid racemization in dentine: What about caries-affected teeth? Int. J. Legal Med. 2018; 132(2): 623–628. PubMed Abstract | Publisher Full Text\n\nMinegishi S, Ohtani S, Noritake K, et al.: Preparation of Dentin Standard Samples for Age Estimation Based on Increased Aspartic Acid Racemization Rate by Heating. Legal Med. 2019; 38(March): 25–31. PubMed Abstract | Publisher Full Text\n\nSibel, Özdemir K: Age determination of fossils collected from Karabük, Safranbolu, Bulak river area by using amino acid racemization method. Communications Faculty of Science University of Ankara Series C Biology Geological Engineering and Geophysical Engineering. 2018; 27(1): 25–36. Publisher Full Text\n\nHartomo BT, Soedarsono N, Adrianto AWD, et al.: Review of Biomolecular Methods for Age Estimation in Application of Forensic Odontology. AIP Conf. Proc. 2019; 2193(December).\n\nZapico SC, Gauthier Q, Antevska A, et al.: Identifying Methylation Patterns in Dental Pulp Aging: Application to Age-at-Death Estimation in Forensic Anthropology. Int. J. Mol. Sci. 2021; 22(7). PubMed Abstract | Publisher Full Text | Free Full Text\n\nZapico SC, Thomas C, Zoppis S: Age estimation based on molecular biology approaches. Age Estimation: A Multidisciplinary Approach. Elsevier Inc.; 2019; 213–223.\n\nMárquez-Ruiz AB, González-Herrera L, Luna J d D, et al.: DNA Methylation Levels and Telomere Length in Human Teeth: Usefulness for Age Estimation. Int. J. Legal Med. 2020; 134(2): 451–459. PubMed Abstract | Publisher Full Text\n\nOgata A, Kondo M, Yoshikawa M, et al.: Dental Age Estimation Based on DNA Methylation Using Real-time Methylation-Specific PCR. Forensic Sci. Int. 2022; 340: 111445. PubMed Abstract | Publisher Full Text\n\nParson W: Age Estimation With DNA: From Forensic DNA Fingerprinting to Forensic (Epi)Genomics: A Mini-Review. Gerontology. 2018; 64(4): 326–332. PubMed Abstract | Publisher Full Text\n\nCorreia Dias H, Manco L, Corte Real F, et al.: A blood–bone–tooth model for age prediction in forensic contexts. Biology (Basel). 2021; 10(12): 1–14. Publisher Full Text\n\nCorreia Dias H, Corte-Real F, Cunha E, et al.: DNA methylation age estimation from human bone and teeth. Aust. J. Forensic Sci. 2022; 54(2): 163–176. Publisher Full Text\n\nAdserias-Garriga J, Thomas C, Ubelaker DH, et al.: When Forensic Odontology Met Biochemistry: Multidisciplinary Approach in Forensic Human Identification. Arch. Oral Biol. 2018; 87(May 2017): 7–14. PubMed Abstract | Publisher Full Text\n\nMansour H, Krebs O, Pinnschmidt HO, et al.: Factors Affecting Dental DNA in Various Real Post-mortem Conditions. Int. J. Legal Med. 2019; 133(6): 1751–1759. PubMed Abstract | Publisher Full Text\n\nKondo M, Aboshi H, Yoshikawa M, et al.: A newly developed age estimation method based on CpG methylation of teeth-derived DNA using real-time methylation-specific PCR. J. Oral Sci. 2021; 63(1): 54–58. PubMed Abstract | Publisher Full Text\n\nPrastyo E, Suhartono AW, Auerkari EI, et al.: Performance of forensic age estimation by aspartic acid racemization and DNA methylation: a systematic review. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "353368",
"date": "25 Jan 2025",
"name": "Bofeng Zhu",
"expertise": [
"Reviewer Expertise population genetics",
"forensic science",
"forensic genetics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe author has meticulously conducted a bibliometric analysis of the application of aspartic acid racemization and DNA methylation in forensic age estimation, thereby providing a comprehensive overview of the current research landscape in this domain.\nThrough this analysis, the author has systematically elucidated the principles, advantages, and limitations associated with the use of aspartic acid racemization and DNA methylation for age estimation in forensic science.\nThe conclusions drawn from this study offer significant insights and valuable references for future research endeavors in individual age estimation. The study is undoubtedly of considerable significance.\nHowever, several suggestions are proposed to further enhance the rigor and clarity of the manuscript, which may be beneficial for its publication. Firstly, it is recommended that the bibliometric results be visually represented. Such visualization would facilitate a more immediate and accessible understanding of the data for readers.\nSecondly, the author should provide a detailed explanation of the criteria for inclusion and exclusion, including the specific references and rationale upon which these standards are based.\nThis would enhance the transparency and reproducibility of the study. Lastly, a thorough discussion of the technological platforms underlying aspartic acid racemization and DNA methylation is warranted.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1368
|
https://f1000research.com/articles/13-994/v1
|
02 Sep 24
|
{
"type": "Software Tool Article",
"title": "Clust&See3.0 : clustering, module exploration and annotation",
"authors": [
"Fabrice Lopez",
"Lionel Spinelli",
"Christine Brun",
"Fabrice Lopez",
"Lionel Spinelli"
],
"abstract": "Background\nCytoscape is an open-source software to visualize and analyze networks. However, large networks, such as protein interaction networks, are still difficult to analyze as a whole.\n\nMethods Here, we propose Clust&See3.0, a novel version of a Cytoscape app that has been developed to identify, visualize and manipulate network clusters and modules. It is now enriched with functionalities allowing custom annotations of nodes and computation of their statistical enrichments.\n\nResults As the wealth of multi-omics data is growing, such functionalities are highly valuable for a better understanding of biological module composition, as illustrated by the presented use case.\n\nConclusions In summary, the originality of Clust&See3.0 lies in providing users with a complete tool for network clusters analyses: from cluster identification, visualization, node and cluster annotations to annotation statistical analyses.",
"keywords": [
"interaction networks",
"graph partitioning",
"clustering",
"visualization",
"cluster annotations",
"functional modules",
"statistical enrichment."
],
"content": "Introduction\n\nSeveral years ago, we proposed Clust&See, a Cytoscape1 plug-in that aims to facilitate network clustering and analysis for biologists by providing several original functionalities within a single framework.2 Mainly, the tool allows decomposing a network into disjoint or overlapping clusters using several in-house algorithms,3–5 visualizing those clusters as metanodes linked by several types of edges/relationships, and manipulating the clusters for further detailed visualization, exploration, analyses and comparisons. We have now developed Clust&See3.0 to fit Cytoscape3 new API and added functionalities allowing the user to annotate the nodes and the clusters with orthogonal data as well as to compute statistical enrichments for those annotations. We here provide examples of Clust&See3.0 usage on a protein-protein interaction network, where annotation enrichments are used (i) to functionally annotate the clusters with the Gene Ontology terms describing node functions in order to globally investigate the network and proceed with protein function prediction, and (ii) to discover features associated to clusters by the integration of data on nodes.\n\n\nMethods\n\nBriefly, the classic use of Clust&See2 breaks down into the following phases:\n\nAs in its first version, Clust&See proposes to partition an imported network using three algorithms: FT (Fusion-Transfer), an ascending hierarchical method fusing two clusters iteratively if the fusion results in a modularity gain3; TFIT (iterated Transfer-Fusion),4 a multi-level algorithm in which a vertex transfer procedure is performed to the best adjacent cluster while modularity increases, to finally compute a quotient graph. Both algorithms generate strict network partitions where clusters have no node in common. The third one, OCG (Overlapping Cluster Generator)5 is an ascending hierarchical method fusing two clusters at each step while modularity increases, starting from an overlapping class system. This leads to overlapping clusters where some nodes belong to several clusters.\n\nFor each cluster in a partition, Clust&See provides detailed information about the cluster: a visualization of the cluster's sub-network, and its main topological features (number of nodes, edges, density, etc.)\n\nEach cluster can be viewed and explored independently, either in a compact mode as a metanode, or in an extended mode as the sub-network constituting the cluster (Figure 1). The decomposition of the complete network can be viewed as a set of metanodes linked by edges, the thickness of which is proportional to the number of links between pairs of nodes of the linked metanodes. When clusters are overlapping, another type of link is added between the metanodes to represent the nodes shared between clusters/metanodes. The thickness of this link is then proportional to the number of shared nodes. From this map, the metanodes can be individually switched to the extended mode to visualize the corresponding sub-network, and back. Finally, the user can build a custom map by iteratively adding sub-networks and/or metanodes to obtain a global view of the partition (Figure 1, central panel).\n\nThe central panel shows (1) the starting network in the top left corner, (2) the quotient graph after TFit partitioning where modules are represented by blue nodes with the icon of the corresponding sub-network inside. The size of the node reflects the number of nodes contained by the module. The blue links correspond to the edges linking the modules, their width reflecting the number of involved interactions. (3) In the right low corner, module 60 is shown as an expanded network. As in the former version of Clust&See, the right panel shows the details of the subnetworks forming the modules with their characteristics. The lower panel (former Data panel) contains the results of the different Cluster and Annotation analyses.\n\nThe novel version of Clust&See3.0 now allows the user to annotate and analyze the nodes and the clusters as follows:\n\nIn order to annotate the clusters, Clust&See3.0 allows importing one or more annotation lists, composed of associations between a network node and one or more terms of any nature (see the Use case).\n\nThe annotation file must be a text file and must contain at least two columns: one contains the node identifier (one identifier per line), the second one, the list of terms associated with this identifier, separated by a comma, a semicolon or a tab. The columns can also be separated by a comma, semicolon or tab, as long as the column separator is not the same as the term separator. The annotation import dialog box lets the user select the 2 columns of interest and eliminate any header lines.\n\nAfter import, Clust&See3.0 provides the number and percentage of annotated nodes in the network. Then the annotation process can be performed.\n\nTwo types of enrichment can be computed for each annotation term, using the whole graph as background:\n\n• A one-sided hypergeometric hypothesis test, the null hypothesis of which corresponds to the proportional distribution of the annotation terms between the nodes inside and the nodes outside the cluster. When the p-value of the hypergeometric test is sufficiently low to reject the null hypothesis, this indicates that the nodes of the cluster carry the term more frequently than expected by chance, thus pointing toward a potential enrichment. It should be noted that since this test is applied to all clusters, the Benjamini-Hochberg procedure6 is used to correct for the multiple testing effect on the p-values. The default value is set to p-values < 5.10-2.\n\n• A majority rule, corresponding to a minimum percentage (to be chosen by the user) of nodes annotated to the term among the annotated nodes of the cluster. The default value is set to 50%.\n\nFor each annotation list, the user can perform a statistical analysis of the clusters and the annotation terms, with different goals. At first, a global analysis of the annotations of the partition can be performed. When choosing the “Cluster list” tab, Clust&See3.0 provides for each cluster, (i) the number of nodes in the cluster that have received at least one annotation term, (ii) the number of annotation terms appearing at least once in the cluster, (iii) the number of terms that are statistically enriched in the cluster with a hypergeometric test, or that annotate a majority of cluster nodes (i.e. with a “majority rule”). For both tests, thresholds are set by the user (Figure 1). Finally, (iv) the terms that are enriched in clusters are shown on demand (Figure 2A). This first type of analysis allows getting a global view of the annotation distribution and to quickly identify clusters that are enriched for annotation terms of interest.\n\n(A) “Cluster List” shows the annotation of all clusters; (B) “Cluster Analysis”, all the annotations of cluster 60; (C) “Annotation term analysis”, all the clusters annotated to GO:2001136; (D) “Node list”, the detail of the annotations of each nodes of the cluster. The node names highlighted in green are those annotated to the term of interest, here GO:2001136.\n\nThe second approach concerns the details of statistical analyses by cluster by choosing the “Cluster analysis” tab. Here, the user can select a particular cluster for a detailed study of the annotations of its nodes. Clust&See3.0 then lists the terms annotating the cluster proteins and provides (i) the number of nodes annotated to the term, (ii) the percentage of nodes annotated to the selected term among the total number of cluster nodes, (iii) the p-value of the term according to the hypergeometric test, (iv) the percentage of nodes annotated to the selected term among the total number of annotated cluster nodes (Figure 2B).\n\nThe third approach concerns the details of the statistical analyses by annotation term. When choosing the “Annotation term analysis” tab, the user can select a particular annotation term and Clust&See3.0 reports for each cluster that contains proteins annotated to this term, the same features than previously (Figure 2C). This type of analysis allows having a detailed view on the distribution of a particular annotation term among all the clusters composing the network.\n\nThe tables displaying the results for the clusters are dynamic and can be used to identify the clusters selected in the map and, in the panel detailing the characteristics of the clusters. The reverse is also true: a selected cluster in the map or in the detailed panel is selected in the annotation statistical results tables.\n\nThe minimum system requirements for use of the Clust&See3.0 Cytoscape app include:\n\nHardware:\n\nMemory: 8 GB\n\nMonitor: 1600×900 (HD+) resolution\n\nSoftware:\n\nJava 11 and above\n\nCytoscape 3.8.0 and above\n\n\nUse Case\n\nWe will illustrate how to use Clust&See3.0 by partitioning and annotating the human reference interactome network (HuRI)7 with Gene Ontology8 (network and annotation files are available at https://doi.org/10.5281/zenodo.12570870). We first partitioned the largest connected component of the HuRI network that contains 8149 nodes and 52016 edges, with the TFit algorithm.4 Sixty-seven modules were obtained among which 20 contain more than 4 nodes (Figure 1). After loading the annotation file that contains the list of IDs of the Biological Process Gene Ontology (BP GO) associated to all human genes/proteins, the number of annotated nodes in the network is indicated: 88% of the proteins of HuRI have functional annotations in the BP GO.\n\n• “Cluster list” tab\n\nIn the “C&S Partition” table, under the “Cluster list” tab, all clusters are shown (Figure 2A). As we empirically consider that the smallest clusters are not suitable for computing statistics on annotations, Clust&See3.0 proposes to hide them for clarity’ sake with a check box “Hide small clusters”.\n\nThe number of enriched terms per cluster according to the chosen statistic (“Hypergeometric law” or “Majority rule”) is indicated, and their GO IDs are available in the “Total annotations” column (Figure 2A) (choose “Annotate cluster X/Remove cluster X annotations” or “Annotate all clusters/Remove all cluster annotations”). The list of annotation terms also appears by right clicking on a cluster of interest on the Partition view, under “Clust&See>Annotate cluster”. At this stage, custom annotations can be added manually by the user to tag a cluster of interest. This annotation will also appear in the list of annotation terms in the “Total annotations” column of the “Cluster list” table. This may help having a global quantitative view of the cluster annotations and further analyses.\n\nThe individual investigation of a particular cluster starts also under this tab. For instance, Cluster 60 contains 8/9 nodes annotated (number given in the “Nodes” column), and solely 1 term is statistically enriched among the 40 terms (number given in the “Annotation terms” column) that annotate the proteins of the cluster, when the hypergeometric law with a corrected p-value threshold set at 5.10−2 is chosen.\n\n• “Cluster analysis” tab\n\nThe term GO:2001136 is enriched among the annotations of the proteins of cluster 60 with a corrected p-value of 4,57.10-4, available in “Hyperg p-value” column under the “Cluster analysis” tab (Figure 2B). The most relevant term (i.e. with the lowest p-value) is easily found by using the ranking column containing the corrected p-values for the terms annotating all the proteins of cluster 60. The term GO:2001136 that corresponds to “negative regulation of endocytic recycling”, is annotating 25% of the annotated proteins of the cluster (number in the “Majority percent” column). Two other terms are also annotating 25% of the cluster’s proteins, but with highest p-values i.e. less significant ones. These are GO:0007264 “small GTPase-mediated signal transduction” and GO:0051056 “regulation of small GTPase mediated signal transduction”. Then, switching to the “C&S Details” Table (Figure 2D), under the “Node” tab, that shows the detailed annotations of the nodes of the cluster, we see that the three terms are associated to the same two genes encoding the proteins involved in these functions: ENSG00000175220 (ARHGAP1) and ENSG00000241484 (ARHGAP8). By expanding the cluster 60 on the network panel (Figure 1, central panel), it can be seen that these two proteins do not interact directly but with the product of ENSG00000141985 (SH3GL1), a protein regulating endocytosis by recruiting proteins to the membrane.\n\n• “Annotation term analysis” tab\n\nThen, wondering whether other clusters are also annotated to “negative regulation of endocytic recycling”, we switched to the “Annotation term analysis” tab to focus on a particular annotation and find all clusters enriched for this term. By entering the ID GO:2001136 in the dedicated frame, we found that none of the clusters but cluster 60 is annotated to this term, either using the hypergeometric law or the majority rule computations (Figure 2C).\n\nThe user can therefore choose to annotate this cluster with this enriched term and, if appropriate, to transfer the annotation/function to any not yet annotated node of the cluster. Notably, the nodes contributing to cluster’s annotations are detailed in the “C&S Details” table (Figure 2D).\n\nExport of the annotations and computations as text files are available at each step, as well as a matrix of the whole results under the “Cluster annotation matrix” tab, for further analysis.\n\n\nConclusion/Discussion\n\nClust&See3.0 is a Cytoscape app that allows (i) clustering the nodes of any network, (ii) annotating the clusters with any annotation terms, and (iii) computing their enrichment significance. This versatility of Clust&See3.0 is constituting its advantage compared to other existing Cytoscape enrichment plug-ins. Not only Clust&See3.0 allows as in its previous version loading any partition of the network, even not generated by the app, as long as the graph is completely covered by clusters, but it also allows using any type of data as node annotations, such as user’s experimental or curated data. In contrast, most of the existing apps are mainly centered on Gene Ontology terms or other types of classical annotations (i.e.8,9). Second, the results of Clust&See3.0 permit to get a global view of the distribution of the annotations between the whole set of clusters, as well as their statistical value. For all these reasons, we think Clust&See3.0 will be a valuable tool for the community.\n\n\nEthics and consent\n\nEthics and consent not required.",
"appendix": "Data availability\n\nZenodo: Clust&See3.0: clustering, module exploration and annotation. https://doi.org/10.5281/zenodo.12570870. The project contains the following underlying data:\n\n• go_annot.txt: The protein annotation file extracted from Gene Ontology Biological Process database. 10\n\n• HuRI_CC.txt: The network file containing the largest connect component of the human reference interactome network. 7\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nShannon P, Markiel A, Ozier O, et al.: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13: 2498–2504. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpinelli L, Gambette P, Chapple CE, et al.: Clust&See: a Cytoscape plugin for the identification, visualization and manipulation of network clusters. Biosystems. 2013; 113: 91–95. Publisher Full Text\n\nGuénoche A: Consensus of partitions: a constructive approach. ADAC. 2011; 5: 215–229. Publisher Full Text\n\nGambette P, Guénoche A: Bootstrap clustering for graph partitioning. RAIRO - Operations Research. 2012; 45: 339–352. Publisher Full Text\n\nBecker E, Robisson B, Chapple CE, et al.: Multifunctional proteins revealed by overlapping clustering in protein interaction network. Bioinformatics. 2012; 28: 84–90. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBenjamini Y, Hochberg Y: Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society: Series B (Methodological). 1995; 57: 289–300. Publisher Full Text\n\nLuck K, Kim D-K, Lambourne L, et al.: A reference map of the human binary protein interactome. Nature. 2020; 580: 402–408. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAshburner M, Ball CA, Blake JA, et al.: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25: 25–29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaere S, Heymans K, Kuiper M: BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005; 21: 3448–3449. PubMed Abstract | Publisher Full Text\n\nMerico D, Isserlin R, Stueker O, et al.: Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One. 2010; 5: e13984. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTheories and Approaches of Genomic Complexity: Cytoscape app ClustnSee 3. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "320335",
"date": "10 Sep 2024",
"name": "Anooja Ali",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Deep learning",
"Computer Vision",
"Data mining",
"Computational Biology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors propose Clust&See3.0, an improved version of Cytoscape, for visualizing and manipulating the bioinformatic network clusters. It has additional functionalities , when compared to Cytoscape like custom annotations of nodes. It provided more statistical analysis for cluster evaluation. How does the user interface of Clust&See3.0 compare to previous versions in terms of usability and accessibility for biologists unfamiliar with network analysis? What are the key characteristics of clusters identified in large protein-protein interaction networks using Clust&See3.0? How do these characteristics correlate with biological functions? How does the annotation and enrichment analysis provided by Clust&See3.0 contribute to the accuracy of protein function predictions in complex biological networks? I hope the user feedback on Clust&See3.0's functionalities inform future updates and enhancements to the software. The citations refer to the aligners for creating a huge protein network based on functional similarities among proteins. The next citation uses cytoscape tool with KEGG pathway analysis and GO annotation tool for generating biclusters. It deals with the generation of gene ontology clusters for each category of MF, BP and CC from biclusters.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "12741",
"date": "14 Nov 2024",
"name": "Christine Brun",
"role": "Author Response",
"response": "Dear Referee, We thank you for your positive review on our manuscript and acknowledge your remarks on our work. Please find below our point-by-point response. The authors propose Clust&See3.0, an improved version of Cytoscape, for visualizing and manipulating the bioinformatic network clusters. It has additional functionalities , when compared to Cytoscape like custom annotations of nodes. It provided more statistical analysis for cluster evaluation. - How does the user interface of Clust&See3.0 compare to previous versions in terms of usability and accessibility for biologists unfamiliar with network analysis? Author response: The previous version of Clust&See had been developed as an app for Cytoscape2.8, which had a completely different architecture and is almost not used anymore. The new Clust&See3.0 has been completely re-developed to comply with Cytoscape3 architecture. Clust&See3.0 therefore benefits in term of usability and accessibility for biologists from the Cytoscape3 features. Note that Cytoscape3 is far more intuitive than Cytoscape2. In addition, to increase the usability of Clust&See3.0 user interface compared to the previous version, we have significantly improved the interconnection of graphical elements and their responsiveness to user actions, so that the user's experience can be enhanced. - What are the key characteristics of clusters identified in large protein-protein interaction networks using Clust&See3.0? How do these characteristics correlate with biological functions? Author response: Both versions of Clust&See propose the same 3 algorithms to identify clusters: FT, TFit and OCG. Most of the clusters found by these algorithms display a biological homogeneity, i.e. they contain proteins involved in the same pathway, the same biological process. This is illustrated by our own network biology analyses in different contexts (1–7) as well as by other authors: the algorithms provided by Clust&See have been used in more than 40 analyses (49 citations in Google Scholar since its first publication (8)). - How does the annotation and enrichment analysis provided by Clust&See3.0 contribute to the accuracy of protein function predictions in complex biological networks? Author response: The advantage of Clust&See3 is twofold. First, any annotation file can be loaded in Clust&See3, allowing the user to highlight clusters of interest at a glance. Second, according to the goal of the analysis, the user can choose between (i) the accuracy of the annotation using the hypergeometric law (e.g. to highlight clusters containing nodes annotated with rare terms) and (ii) the homogeneity of the annotation with the majority rule (e.g. to highlight clusters containing nodes annotated with the same terms). 1. Kim DK, Weller B, Lin CW, Sheykhkarimli D, Knapp JJ, Dugied G, et al. A proteome-scale map of the SARS-CoV-2-human contactome. Nat Biotechnol. janv 2023;41(1):140‑9. 2. Katsogiannou M, Andrieu C, Baylot V, Baudot A, Dusetti NJ, Gayet O, et al. The functional landscape of Hsp27 reveals new cellular processes such as DNA repair and alternative splicing and proposes novel anticancer targets. Mol Cell Proteomics. déc 2014;13(12):3585‑601. 3. Zanzoni A, Spinelli L, Braham S, Brun C. Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins. Microbiome. 10 août 2017;5(1):89. 4. Zanzoni A, Spinelli L, Ribeiro DM, Tartaglia GG, Brun C. Post-transcriptional regulatory patterns revealed by protein-RNA interactions. Sci Rep. 13 mars 2019;9(1):4302. 5. Zanzoni A, Brun C. Integration of quantitative proteomics data and interaction networks: Identification of dysregulated cellular functions during cancer progression. Methods. 2016;93:103‑9. 6. Ribeiro DM, Zanzoni A, Cipriano A, Delli Ponti R, Spinelli L, Ballarino M, et al. Protein complex scaffolding predicted as a prevalent function of long non-coding RNAs. Nucleic Acids Res. 25 janv 2018;46(2):917‑28. 7. Ribeiro DM, Prod’homme A, Teixeira A, Zanzoni A, Brun C. The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization. Nucleic Acids Res. 9 juill 2020;48(12):6491‑502. 8. Spinelli L, Gambette P, Chapple CE, Robisson B, Baudot A, Garreta H, et al. Clust&See: a Cytoscape plugin for the identification, visualization and manipulation of network clusters. BioSystems. août 2013;113(2):91‑5. On behalf of the authors, Christine Brun"
}
]
},
{
"id": "329845",
"date": "23 Oct 2024",
"name": "Ju Xiang",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Data mining",
"ComputationalBiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors reported Clust&See3.0, a new version of Cytoscape app “Clust&See” for the identification, visualization and manipulation of network clusters. It provided functionalities allowing custom annotations and computation of statistical enrichments. It may be a useful tool of network cluster analyses.\n\n--It would be better to provide introduction for other tools of the same type in section introduction. --It is suggested to provide a table for comparing the different versions of Clust&See and other tools of the same type. --It is helpful for users to choose and use tools if the complexity of time and space for the algorithms in the tool can be provided. --Furthermore, it would be even better if comparisons with other tools could be provided.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "12742",
"date": "14 Nov 2024",
"name": "Christine Brun",
"role": "Author Response",
"response": "Dear Referee, We thank you for your positive review on our manuscript and acknowledge your remarks on our work. Please find below our point-by-point response. The authors reported Clust&See3.0, a new version of Cytoscape app “Clust&See” for the identification, visualization and manipulation of network clusters. It provided functionalities allowing custom annotations and computation of statistical enrichments. It may be a useful tool of network cluster analyses. We thank the reviewer to recognize the utility of our work. --It would be better to provide introduction for other tools of the same type in section introduction. Cytoscape Apps proposing in a single tool the identification of clusters AND their annotation with custom annotation files are seldom. We add this information in the introduction section in a new paragraph. “Although Cytoscape Apps allowing the identification of clusters such as ClusterMaker 6, cluster annotations and computation of enrichment statistics such as BinGO 7, or combinations of those as proposed by Functional Enrichment Collection (https://apps.cytoscape.org/apps/functionalenrichmentcollection) do exist, those proposing in a single tool the identification of clusters and their annotation with custom annotation files are seldom. We therefore felt there was room for a tool such as Clust&See3.0, that performs all in a single workflow.” --It is suggested to provide a table for comparing the different versions of Clust&See and other tools of the same type. The previous Clust&See version is completely included in the new one. The differences between the two App versions lie in the statistical enrichment functionalities newly implemented in Clust&See3. Regarding other tools of the same type, the comparison is difficult for several reasons. As explain now in the text, other tools propose either to compute clusters, or to annotate them (one by one). Then collections such as Functional Enrichment Collection proposes to install several of these individual tools at once, but the user must perform the transfer of the results of the first tool to the second, etc., whereas Clust&See3.0 provided everything at once. Finally, CyCommunityDetection detect communities and annotate all clusters but not with custom annotations. In addition, it runs on a remote sever whereas Clust&See3.0 is locally installed, thus avoiding issues due to server accessibility or network connection. --It is helpful for users to choose and use tools if the complexity of time and space for the algorithms in the tool can be provided. OCG runs in O(n3) with default parameters. The two others run faster. In an independent evaluation (9), we can read “OCG is an elite algorithm of high time efficiency…” --Furthermore, it would be even better if comparisons with other tools could be provided. As explained previously, a formal comparison is difficult, mainly because the purpose of the tools being different, the functionalities are different. However, all our partitioning/clustering algorithms have been assessed previously by us and others. For instance, the performances of the 3 algorithms (i.e. FT, TFit, OCG) have been recognized to outperform 4 other algorithms on different biological datasets by measuring 5 performance indices (1). The comparison of OCG performances with other algorithms has also been performed by us, in the original publication (2) and by others (3). 1. Sharma P, Ahmed HA, Roy S, Bhattacharyya DK. Unsupervised methods for finding protein complexes from PPI networks. Netw Model Anal Health Inform Bioinforma. 2 juin 2015;4(1):8. 2. Becker E, Robisson B, Chapple CE, Guénoche A, Brun C. Multifunctional proteins revealed by overlapping clustering in protein interaction network. Bioinformatics. 1 janv 2012;28(1):84‑90. 3. Ding Z, Zhang X, Sun D, Luo B. Overlapping Community Detection based on Network Decomposition. Sci Rep. 12 avr 2016;6(1):24115. On behalf of the authors, Christine Brun"
}
]
},
{
"id": "320337",
"date": "31 Oct 2024",
"name": "Lun Hu",
"expertise": [
"Reviewer Expertise Complex network analysis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper, the authors propose Clust&See3.0, a novel version of a Cytoscape app that has been developed to identify, visualize and manipulate network clusters and modules. Here are some comments that may be helpful.\n1. The introduction section needs to be further strengthened. Since the proposed Clust&See is a Cytoscape for network clustering and analysis of biological data, the authors should provide relevant background and current needs. This will help to better illustrate the significance and applicability of the Cytoscape.\n2. In the methods section, for the use of Clust&See3, the authors should provide a general process. Particularly, the differences between Clust&See3 and Clust&See should be emphasized.\n3. The novel version of cluster&see3.0 allows users to annotate and analyze nodes and clusters, which is indeed very favorable. However, in the paper, the authors should focus on the advantages and implications of doing so.\n4. In the conclusion section, the authors should briefly discuss the limitations and future improvements of Clust&See3.0.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? No\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? No\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? No",
"responses": [
{
"c_id": "12878",
"date": "27 Nov 2024",
"name": "Christine Brun",
"role": "Author Response",
"response": "Dear Referee, We thank you for your positive review of our manuscript and acknowledge your remarks on our work. Please find below our point-by-point response. The introduction section needs to be further strengthened. Since the proposed Clust&See is a Cytoscape for network clustering and analysis of biological data, the authors should provide relevant background and current needs. This will help to better illustrate the significance and applicability of the Cytoscape. The current revised version of the introduction is answering this remark. The introduction has been modified to underline the needs. “Although Cytoscape Apps allowing the identification of clusters such as ClusterMaker 6, cluster annotations and computation of enrichment statistics such as BinGO 7, or combinations of those as proposed by Functional Enrichment Collection (https://apps.cytoscape.org/apps/functionalenrichmentcollection) do exist, those proposing in a single tool the identification of clusters and their annotation with custom annotation files are seldom. We therefore felt there was room for a tool such as Clust&See3.0, that performs all in a single workflow.” In the methods section, for the use of Clust&See3, the authors should provide a general process. Particularly, the differences between Clust&See3 and Clust&See should be emphasized. The Method section is following the general process: 1- Decompose a network, 2- Cluster Visualization and exploration, 3- Importing nodes annotations, 4- Annotation rules, statistical enrichments, 5- Cluster and annotation analyses. While the two first steps were already possible with the first version of Clust&See, the step 3 to 5 are specific to Cluts&See3.0. Clust&See3.0 provides the handling of the annotations. In fact, Clust&See is included within Clust&See3.0 but has been re-coded to fulfill the Cytoscape3 format. 3. The novel version of cluster&see3.0 allows users to annotate and analyze nodes and clusters, which is indeed very favorable. However, in the paper, the authors should focus on the advantages and implications of doing so. As explained in the manuscript, the advantage of annotating clusters with Clust&See3.0 is the possibility of using custom annotations, allowing the analysis to exactly fit the will and the question of the user. Then, “For each annotation list, the user can perform a statistical analysis of the clusters and the annotation terms, with different goals. At first, a global analysis of the annotations of the partition can be performed. “…”This first type of analysis allows getting a global view of the annotation distribution and to quickly identify clusters that are enriched for annotation terms of interest.” 4. In the conclusion section, the authors should briefly discuss the limitations and future improvements of Clust&See3.0. The limitations of Clust&See3.0 could reside in the performances of the clustering algorithms. However, all our partitioning/clustering algorithms have been assessed previously by us and others. For instance, the performances of the 3 algorithms (i.e. FT, TFit, OCG) have been recognized to outperform 4 other algorithms on different biological datasets by measuring 5 performance indices (1). The comparison of OCG performances with other algorithms has also been performed by us, in the original publication (2) and by others (3). 1. Sharma P, Ahmed HA, Roy S, Bhattacharyya DK. Unsupervised methods for finding protein complexes from PPI networks. Netw Model Anal Health Inform Bioinforma. 2 juin 2015;4(1):8. 2. Becker E, Robisson B, Chapple CE, Guénoche A, Brun C. Multifunctional proteins revealed by overlapping clustering in protein interaction network. Bioinformatics. 1 janv 2012;28(1):84‑90. 3. Ding Z, Zhang X, Sun D, Luo B. Overlapping Community Detection based on Network Decomposition. Sci Rep. 12 avr 2016;6(1):24115. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? No Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? No As stated in the manuscript, the code is available on github and zenodo : https://github.com/fafa13/ClustnSee-3, https://doi.org/10.5281/zenodo.13220735 Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? No On the behalf of all authors, Christine Brun"
}
]
}
] | 1
|
https://f1000research.com/articles/13-994
|
https://f1000research.com/articles/13-656/v1
|
18 Jun 24
|
{
"type": "Research Article",
"title": "Health care workers hospitalized for COVID-19 in Liberia: who were they, and what were their outcomes?",
"authors": [
"Darius B. Lehyen",
"Louis Ako-Egbe",
"Emmanuel Dwalu",
"Benjamin T. Vonhm",
"Pruthu Thekkur",
"Rony Zachariah",
"Luke Bawo",
"Louis Ako-Egbe",
"Emmanuel Dwalu",
"Benjamin T. Vonhm",
"Pruthu Thekkur",
"Rony Zachariah",
"Luke Bawo"
],
"abstract": "Background Sustaining a ‘fit-for-purpose’ health workforce requires a better understanding of the health care worker cadres that are affected during pandemics and their outcomes. In hospitalized health care workers with confirmed COVID-19 between March 2020 and May 2023 in Liberia, we determined the hospitalization and case fatality rates, type of health care worker cadres affected, their demographic and clinical characteristics and hospital exit outcomes.\n\nMethods This was a cohort study using routine data extracted from hospitalization forms for health care workers in 24 designated COVID-19 treatment facilities in Liberia.\n\nResults Of the 424 health care workers with COVID-19, hospitalization rates progressively declined between 2020 and 2023, with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021 with no deaths thereafter. Among those hospitalized, the highest proportions were nursing cadres with 191(45%), physicians with 63 (15%) and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 infection was the health facility (326, 89%). COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections. Of the 424 who were hospitalized, 412 (97%) recovered, 9 (2%) died and 3 (1%) either left against medical advice or absconded. Of the nine deaths, none were vaccinated, seven had moderate-to-severe disease but were not referred to specialized COVID-19 treatment centers.\n\nConclusions The hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia.",
"keywords": [
"SORT IT",
"Universal Health Coverage",
"Health Systems Strengthening",
"Infection Prevention Control",
"Pandemics",
"Operational Research",
"STROBE Guidelines",
"EpiCollect5"
],
"content": "Introduction\n\nAn umbrella review of 13 systematic reviews from 1,230 studies including 1,040,336 COVID-19 confirmed cases revealed a global infection rate of 14.5% among health care workers, and an overall case fatality of nine deaths per 1,000 infections.1 These rates could have been accentuated by health-related challenges among one-third of the health care workers such as poor sleep quality, mental health issues, work-related stress and skin injuries associated with use of personal protective equipment.2 There was also limited access to COVID-19 vaccines.3\n\nIn the African region, the World Health Organisation (WHO) estimated that over 10,000 health care workers were infected with COVID-19. Liberia reported a total of 8,090 confirmed COVID-19 cases and 404 healthcare worker infections to WHO, ranking it among the top three with the highest country-specific health care worker infection rates in the region.4\n\nPrior to the COVID-19 pandemic, the 2014-2016 Ebola outbreak in Liberia took a devastating toll on health care workers with 372 infections and 184 Ebola-related deaths which reduced the health workforce by 8.1%.5 The country has one of the lowest core health care worker density ratios in the world with 12.8 core health care workers per 10,000 population (WHO minimum = 44.5 per 10,000 habitants). For example, in the USA, this figure stands at 82 per 10,000 (WHO - health-workforce). Thus, preventing health care worker deaths is a top priority for sustaining the Liberian health system and achieving Universal Health Coverage.6\n\nThe dire health care worker situation in Liberia underpins the importance of health care worker safety and the need to effectively monitor health care worker infections using standardized data surveillance and clinical management tools. During outbreaks, such data collection tools are often not available, and countries may be “caught unprepared”. Thus, there is the need to establish timely standardized and regular surveillance, case management and reporting systems. Data validation during outbreaks is also a challenge as the health system gets rapidly overwhelmed and busy health care workers end up often unable to devote time for data validation. The situation was no different in Liberia which, in 2020, introduced a paper-based data collection form for health care workers hospitalized with COVID-19. To date, there has been no formal audit of the completeness and usefulness of this data in informing outbreak management.\n\nAn operational research priority in Liberia is to better understand the health care worker cadres that were affected by COVID-19, their clinical course, and outcomes. The existing data collection forms provide an opportunity to analyze such information using an operational research lens. Such information could contribute towards sustaining a ‘fit-for-purpose’ health workforce and improving the monitoring system in preparation for future outbreaks.7 A PUBMED search revealed no studies from Liberia (or neighbouring countries) that assessed the quality of COVID-19 data for health care workers hospitalized to health facilities and their outcomes.\n\nWe thus aimed to describe the characteristics of hospitalized health care workers with COVID-19 in Liberia and their outcomes. In all hospitalized health care workers with confirmed COVID-19 in Liberia between March 2020 and May 2023, our specific objectives were to determine a) the COVID-19 hospitalization and case fatality rates by year, b) the type of health care worker cadres affected along with their demographic and clinical characteristics, c) the medical interventions administered and d) the health facility exit outcomes. We also assessed the proportion of missing and unknown data.\n\n\nMethods\n\nCohort study using routine country-wide health facility data.\n\nLiberia is a country on the West African coast, bordered by Sierra Leone to the northwest, Guinea to the north, the Ivory Coast to the east, and the Atlantic Ocean to the south. It has a population of around 5 million and is divided into 15 counties (with Montserrado county being the most populated and hosting the capital city of Monrovia) and 98 districts.\n\nThe health system is tiered and includes a primary level (primary health clinics), a secondary level (health center and county/regional hospitals) and a tertiary level (national specialized hospitals). The first case of COVID-19 in Liberia was confirmed on 16th March 2020, and by July 2023 there had been a total of 8,090 confirmed cases.5 Vaccination of health care workers started in late 2021. By 30 April 2023, complete COVID-19 vaccination coverage in the general population was 81% and was similar in health care workers (WHO - COVID-19 vaccination drive).\n\nScreening, diagnosis, and management of COVID-19 in health care workers\n\nCOVID-19 was managed according to the national guideline.8 In brief, all health care workers with clinical signs (e.g., fever, cough, sore throat) were tested for the COVID-19 virus (SARS-CoV-2) using nasopharyngeal samples. SARS-CoV-2 was confirmed using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).9 Those with moderate to severe clinical symptoms were screened for common comorbidities (e.g., HIV, diabetes mellitus, asthma, and hypertension). Clinical management was based on four principles: early identification, early isolation and quarantine, early diagnosis, and early treatment.\n\nIn terms of clinical management, patients were graded according to WHO criteria as: mild, moderate, severe and critical (Table 1).8 Asymptomatic patients with mild disease were monitored at home and those with symptomatic disease (irrespective of severity) were hospitalized on clinical discretion of the medical team. Symptomatic patients were managed at one of the COVID-19 treatment centers. Those with severe and critical disease were to be administered oxygen by nasal cannulae or face mask, and if needed, hospitalized to an intensive care unit (ICU). Mechanical respiratory support (where available) and management of complications (pneumonia, sepsis, acute respiratory distress, and other life-threatening conditions) were to be done in ICUs.\n\n\n\n• RR>28-32bpm\n\n• Cyanosis\n\n• Chest in-drawing\n\nCOVID-19 facility exit outcomes were standardized as recovered and discharged, died, abandoned (patient left without notice) and left-against-medical-advice.\n\nThe study population included all hospitalized health care workers with confirmed COVID-19 from March 2020 to May 2023 in Liberia. The study was conducted between July 2023 and March 2024.\n\nThere were 962 functional health facilities in the country of which 24 were designated as COVID-19 treatment facilities and located in fourteen counties. Twenty-two of these facilities were COVID-19 treatment units (first level) and two were specialized centers with an intensive care unit (referral level). The study sites were the 24 designated COVID-19 treatment facilities.\n\nIndividual patient information from the various COVID-19 treatment units and centres were entered on data forms by the attending clinicians. The county case management officers in collaboration with the county surveillance team collated this information which was centralized at the National Public Health Institute and the Ministry of Health.\n\nAll data in the national COVID-19 database was reviewed by the principal investigator and a line list of health care workers hospitalized for COVID-19 between March 2020 and May 2023 was created. Thereafter, the principal investigator visited all treatment facilities and traced the individual patient cards for cross-validation of data in the line-list. The central Incident Management Team provided oversight and then entered all data into an EpiCollect5 mobile cloud-based application for further validation and analysis.\n\nData variables included patient number, admitting COVID-treatment facility, health care worker type, demographic and clinical characteristics, co-morbidities, vaccination status, medical interventions, complications, and facility exit outcomes. The sources of data included the COVID-19 national health care worker database, individual patient cards in COVID-19 treatment facilities and the national database of human resources for health.\n\nData was analyzed using (Stata software version 16) (College Station, TX, USA: Stata Corp LLC. Free alternatives to Stata are RStudio or JASP). Countrywide geographic distribution of health care workers infected with COVID-19 was presented graphically per county using QGIS software 3.36.2 (Figure 1).\n\nThe demographic characteristics, clinical characteristics, vaccination status and hospital exit outcomes were summarized using frequencies and percentages. Hospitalization rates for COVID-19 among health care workers were calculated by standardizing the numbers of health care workers hospitalized by year with the total number of health care workers registered in that year and expressed by 1,000 health care workers.\n\nPermission for using the data was obtained from the Ministry of Health of Liberia. National Ethics approval was obtained from the Liberian National Ethics Review Board (Number 23-09-391, dated 27th September 2023) and international approval was received from the Union Ethics Advisory Group of the Center for Operational Research of the International Union against Tuberculosis and Lung Disease, Paris, France (EAG number 18/23, dated 8th September 2023). As we used secondary health facility data, the issue of informed consent did not apply.\n\n\nResults\n\nOf the 424 health care workers hospitalized with COVID-19 in Liberia, the highest number was in 2020 (247 cases) followed by 2021 (149 cases). Hospitalizations showed a linear declining trend from 2020 to 2023 (Table 2, chi-square for linear trend=321, P<0.001).\n\nSimilarly, the rate of hospitalization declined between 2020 and 2023 with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021. There were no deaths in 2022 and 2023.\n\nFigure 1 shows countrywide geographic distribution of health care workers infected with COVID-19 graphically per county. The highest number of hospitalizations were in Montserrado and Lofa counties.\n\nTable 3 shows the type of health cadres hospitalized and their characteristics. Among those hospitalized, the highest proportions were nursing cadres (nurses, midwives, and nursing aids) with 191 (45%) hospitalized, followed by physicians (doctors and physician assistants) with 63 (15%), and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 exposure (presumed source of infection) was the health facility (326, 89%). At the time of hospitalization, COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections.\n\n$ Column percentage.\n\n* Other Health care workers includes vaccinators, drivers, hospital security staff, pharmacists and dispensers.\n\n# Only among those who reported to have been exposed to a person with similar illness.\n\n@ Multiple symptoms are possible. Thus, total does not add up to 424.\n\nBetween one and ten percent of clinical variables related to demographics and clinical features had either missing information and/or unknown information.\n\nTable 4 shows the medical interventions and recorded complications. There were three individuals who received oxygen with oxygen concentrators. Five patients had life-threatening sepsis as a complication but all five were managed in first level-facilities (treatment units). There was one to three percent of missing information in variables related to medical interventions and complications.\n\nOf 424 health care workers hospitalized, 412 (97%) recovered and were discharged, 9 (2%) died and 3 (1%) either left against medical advice or absconded (Table 5). Of the nine who died, none were vaccinated, seven had moderate-to-severe disease and all were hospitalized in non-specialized COVID-19 treatment units. In two deaths, disease severity was not recorded.\n\n\nDiscussion\n\nThis first country-wide study from Liberia on health care worker hospitalizations for COVID-19 showed that clinical and laboratory personnel were the most affected, the main source of infection was the health facility and only 20% of health care workers were vaccinated. The majority (91%) of all hospitalizations were for mild symptomatic infections and this applied as well to the 35% of hospitalizations in specialized centres. Among those who died with moderate to severe infection, none had benefited from hospitalization in specialized centres.\n\nThe study findings are important as they are a clarion call for improving health care worker safety, strengthening infection prevention and control, and offering health care workers priority access to vaccination. In the early part of the pandemic, when vaccines were in short supply and/or equity issues were in play,10 vaccinating health care workers should have been a top-level priority to sustain a ‘fit for purpose’ health workforce. This strategy is akin to “treating the pilots in a plane flying at 30,000 feet before attending to passengers”. However, Liberia like most other African countries did not have sufficient access to COVID-19 vaccines.11 This study also highlights the importance of early institution of triage and referral systems to ensure that individuals with moderate to critical infections and most in need of hospitalized care, are adequately catered for during an outbreak.\n\nThe study strengths are that the research subject was a national operational research priority and thus relevant, and all health facilities in the country were included making it likely that the study was representative of the situation on the ground. We also ensured that data were cross-validated with individual patient cards at all study sites, and we adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.12\n\nOne of the study limitations is that we had missing and/or unknown variables (one to ten percent) in the patient cards, highlighting the need for enhanced oversight for improving the quality of data by the national and county incident management teams. The fact that these teams have already taken corrective steps with health facilities shows the useful synergy developed between operational research and the strengthening of the current monitoring and evaluation system. Another limitation is that we did not know the exact reasons for the observed decline in numbers of hospitalized cases by year and whether this was related to increasing vaccination coverage over time and/or changes in hospitalization practices or the virulence of the circulating SARS-CoV-2 virus strains.\n\nThis study has a number of policy and practice implications. First, clinical and laboratory staff constituted 70% of all hospitalizations and their predominant source of infection was the health facility. This highlights that health facilities were ‘hot spots’ for the acquisition and transmission of infection. The way forward is to ensure regular IPC assessments in all health facilities13 and ensure the availability of on-site ‘safety stocks’ of Personal Protective Equipment (PPE) material as part of the preparedness strategy for future outbreaks. Furthermore, the fact that there were nine health care worker deaths from COVID-19 compounds the already low health care worker density in Liberia and this may have contributed to disruptions in routine health service delivery.\n\nSecond, the fact that the majority of hospitalizations (91%), including a considerable proportion in specialized centres, were for mild symptomatic infections is concerning. It implies that COVID-19 treatment sites largely served as ‘isolation facilities’ rather than treatment centres. From a health system perspective, this is disadvantageous for two reasons: a) available beds get unnecessarily filled and those genuinely meriting hospitalized care may risk being turned away, and b) large numbers of individuals with mild infections hospitalized in health facilities increases the risk of disease transmission to both health care workers and the community at large.\n\nClogging up the health system will also have a crippling effect resulting in those with moderate to severe disease not being promptly identified and referred to higher level health facilities. This seems to have been the case since nine health care workers who died should have been referred to specialized centres but this did not happen. Five individuals identified with complicated sepsis were also not referred to specialized treatment centres. Such shortcomings in the triage and referral system should be corrected for future outbreaks and public health emergencies.\n\nThird, during outbreaks, there is need for data and information in ‘real-time’ to inform and enable decision makers to institute prompt actions that can uphold the capability and accountability of health systems.14 A survey conducted by the WHO in 2022 showed that 92% of all countries were still facing COVID-19 related disruptions which affected all health service delivery platforms.15 In Liberia, as of July 2021, utilization of essential maternal and reproductive health services was lower than pre-pandemic trends. Similarly, there were substantial disruptions in outpatient services (down by 17%), family planning consultations (down by 36%), post-natal care first visit (down by 21%), ante natal care first visit (down by 19%).16 ‘Real-time intelligence’ would help steer the health system out of such trouble as has been demonstrated in some African countries.17,18 The use of mobile phone applications (such as EpiCollect5) and cloud-based data storage can provide a useful adjunct to emergency responses and should be explored in Liberia and neighbouring countries.17,18\n\n\nConclusions\n\nIn conclusion, this country-wide study from Liberia showed that hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia.",
"appendix": "Data availability\n\nRequests to access these data should be sent to the corresponding author who will liaise with the Department of Infectious Diseases and Epidemiology (DIDE) at the National Public Health Institute of Liberia. All requests for access to the dataset will need to be submitted to a data committee of the DIDE.\n\n\nAcknowledgements\n\nThis research was conducted through the Structured Operational Research and Training Initiative (SORT IT), a global partnership led by TDR, the Special Programme for Research and Training in Tropical Diseases hosted at the World Health Organization. The specific SORT IT program that led to this publication is a SORT IT partnership with the WHO Emergency Medical Teams (Geneva), WHO-AFRO (Brazzaville), WHO Country Offices and Ministries of health of Guinea, Liberia, Sierra Leone, and the Democratic Republic of the Congo, the Infectious Diseases Data Repository (IDDO); The International Union Against Tuberculosis and Lung Diseases, Paris, France and South East Asia offices, Delhi, India; The Tuberculosis Research and Prevention Center Non-Governmental Organization, Yerevan, Armenia; I-Tech, Lilongwe, Malawi; Medwise solutions consultancy, Nairobi, Kenya; All India Institute of Medical Sciences, Hyderabad, India; and the National Training and Research Centre in Rural Health, Maferinyah, Guinea.\n\nThere should be no suggestion that WHO endorses any specific organization, products or services. The views expressed in this article are those of the authors and do not necessarily reflect those of their affiliated institutions. The use of the WHO logo is not permitted.\n\n\nReferences\n\nChutiyami M, Bello UM, Salihu D, et al.: COVID-19 pandemic-related mortality, infection, symptoms, complications, comorbidities, and other aspects of physical health among healthcare workers globally: An umbrella review. Int. J. Nurs. Stud. 2022; 129: 104211. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGalanis P, Vraka I, Fragkou D, et al.: Impact of personal protective equipment use on health care workers’ physical health during the COVID-19 pandemic: A systematic review and meta-analysis. Am. J. Infect. Control. 2021; 49(10): 1305–1315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAckah M, Ameyaw L, Salifu MG, et al.: COVID-19 vaccine acceptance among health care workers in Africa: A systematic review and meta-analysis. PLoS One. 2022; 17(5 May): 1–15. Publisher Full Text\n\nWHO: World Health organization. WHO Liberia 2022 Annunal Report: Rebuilding Liberia’s health system.2022.\n\nMOH. Ministry of Health: Government of Liberia. Investment plan for building a resilient health system in Liberia. Ministry of Health; 2015; vol. 12.\n\nMOH/LISGIS: Ministry of Health of Liberia and Institute of Statistics and Geo-Information Services. Liberia: Liberia Demographic and Health Survey; 2019-20. 2019; p.594.\n\nMOH: Ministry of Health. Essential Package for Health Services for Univsersal Health Coverage.2022.\n\nMOH: Ministry of Health and NPHIL. National Public Health Institute of Liberia. Interim guidance on clinical care for patients with COVID-19 in Liberia.2021.\n\nMOH: Ministry of Health. Interim guidance on clinical care for patients with COVID-19 in Liberia. 2022.clinical-care-for-patients-with-covid-19-in-liberia.\n\nVan De Pas R, Widdowson MA, Ravinetto R, et al.: COVID-19 vaccine equity: a health systems and policy perspective. Expert Rev. Vaccines. 2022; 21(1): 25–36. PubMed Abstract | Publisher Full Text\n\nLawal L, Aminu Bello M, Murwira T, et al.: Low coverage of COVID-19 vaccines in Africa: current evidence and the way forward. Hum. Vaccin. Immunother. 2022; 18(1): 1–5.\n\nVon Elm E, Altman DG, Egger M, et al.: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. Bull. World Health Organ. 2007; 85(11): 867–872. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKabego L, Balde T, Barasa D, et al.: Analysing the implementation of infection prevention and control measures in health care facilities during the COVID-19 pandemic in the African Region. BMC Infect. Dis. 2023; 23(1): 1–8.\n\nRujumba J, Byamugisha R: Publishing operational research from “real life” programme data: A better form of accountability. Trop. Med. Int. Heal. 2012; 17(1): 133–134. PubMed Abstract | Publisher Full Text\n\nWHO: Pulse survey on continuity of essential health services during the COVID-19 pandemic. World Health Organization Interim Report; 2020; pp. 1–21.\n\nShapira G, Ahmed T, Drouard SHP, et al.: Disruptions in maternal and child health service utilization during COVID-19: Analysis from eight sub-Saharan African countries. Health Policy Plan. 2021; 36(7): 1140–1151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHarries AD, Thekkur P, Mbithi I, et al.: Real-time operational research: Case studies from the field of tuberculosis and lessons learnt. Trop Med Infect Dis. 2021; 6(2): 1–13. Publisher Full Text\n\nThekkur P, Tweya H, Phiri S, et al.: Assessing the Impact of COVID-19 on TB and HIV. Trop Med. Infect. Dis. 2021; (January 2020); 1211."
}
|
[
{
"id": "316429",
"date": "26 Aug 2024",
"name": "Kenneth Nugent",
"expertise": [
"Reviewer Expertise Critical care medicine"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThese authors have analyzed the healthcare workers in Liberia who had confirmed COVID-19 infection between March 2020 and May 2023. The study extracted routine data from hospitalization forms in 24 designated COVID-19 treatment facilities. In general, they provide a complete overview of these workers and their characteristics. The following results seem important. None of the healthcare workers who died had been vaccinated. Seven of the nine who died had moderate to severe disease but were not referred to specialized treatment centers. Many patients with mild disease were hospitalized, possibly resulting in an unnecessary use of resources. This project provides an outline which other healthcare facilities and/or organizations could use to analyze COVID-19 infections. In addition, it should provide the healthcare authorities in Liberia information to help them plan for the next epidemic.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12305",
"date": "27 Aug 2024",
"name": "Darius B. Lehyen",
"role": "Author Response",
"response": "Thanks so kindly to the reviewer for highlighting the following key points on my submission 1. That the work was clearly and accurately presented and cited the current literature. 2. That the study design was appropriate and the work is technically sound. 3. That there are sufficient details of methods and analysis provided to allow replication by others. 4. That the statistical analysis and its interpretation is appropriate. 5. That all the source data underlying the results are available to ensure full reproducibility and 6. That the conclusions drawn are adequately supported by the results I authorize that I have read the reviewer response to my submission and I believe that he has a suitable level of expertise to confirm that my article is of an acceptable scientific standard."
}
]
},
{
"id": "328861",
"date": "26 Oct 2024",
"name": "Helena C Maltezou",
"expertise": [
"Reviewer Expertise Epidemiology",
"healthcare workers occupational risk",
"vaccination",
"COVID-19"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an interesting study. Please find below my comments:\nAbstract: please provide p-values. It is not clear why HCP were mostly not vaccinated. Were HCP prioritized for COVID-19 vaccination in Liberia? Please clarify. Discussion: The authors should compare their findings with those reported by other researchers. Please move the strengths and limitations paragraph before the conclusion (last) paragraph.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12731",
"date": "14 Nov 2024",
"name": "Darius B. Lehyen",
"role": "Author Response",
"response": "Thanks so very much to the reviewer for highlighting the following key points on my submission Abstract: P-value had been provided in the abstract section of the article It is not clear why HCP were mostly not vaccinated. Were HCP prioritized for COVID-19 vaccination in Liberia? Please clarify. Author response: HCP were not vaccinated because in the early part of the pandemic, vaccines were in short supply and equity issues were in play. Offering health care workers priority access to COVID-19 vaccination was an issue from the onset of the pandemic in Liberia and this is mentioned in the article. Discussion: The authors should compare their findings with those reported by other researchers. Author response: The findings of this article were compared with other researchers findings in the last paragraph in discussion. Author response: The strengths and Limitations were moved to the last paragraph before the conclusion of the article."
}
]
}
] | 1
|
https://f1000research.com/articles/13-656
|
https://f1000research.com/articles/13-1064/v1
|
17 Sep 24
|
{
"type": "Research Article",
"title": "The quality of life in Thai senior table tennis players",
"authors": [
"Oam To-aj",
"Sornpravate Krajangkantamatr",
"Pennapa Saenkla",
"Weerasak Putthasri",
"Navaporn Chanbanchong",
"Apithai Bumrungpanictarworn",
"Oam To-aj",
"Pennapa Saenkla",
"Weerasak Putthasri",
"Navaporn Chanbanchong",
"Apithai Bumrungpanictarworn"
],
"abstract": "Background Table tennis presented a unique and accessible sport for people of all ages, particularly seniors compared to other sports.\n\nMethods This study utilized a quantitative with 136 Table tennis players those who registered for attending in the Thailand Master Table tennis Championships 2024 which hosted in January 2024 at Chiangmai. The questionnaire based on the measurement quality of life, WHOQOL Thai version, and analyzed using Descriptive statistics, Pearson Correlation.\n\nResults Pearson correlation coefficients between the scores of the quality of life in four dimensions and the overall score revealed significant correlations (p < 0.01) with all dimensions, including physical health, psychological health, social relationships, and environmental health.\n\nConclusions Playing Table tennis for senior in the tournament level helped to improve the quality of life in all domains.",
"keywords": [
"Senior",
"Table Tennis",
"Quality of life",
"physical health",
"psychological health"
],
"content": "Introduction\n\nParticipation in sports has been a well-established phenomenon with documented positive influences on quality of life (Peráčková & Peráček, 2020). Engaging in physical activity, a key component of sports participation, yielded a range of benefits for individuals. These included improved brain health, weight management, disease prevention, enhanced bone and muscle strength, and a greater capacity for performing daily activities (Centers for Disease Control and Prevention (CDC), 2023). Importantly, research has also shown that physical activity was highly effective in managing anxiety, depression symptoms, and distress across various elderly populations (Singh et al., 2023).\n\nQuality of life, a multifaceted concept encompassing physical, psychological, social, and environmental well-being (World Health Organization [WHO], 2024), reflects an individual’s perception of their life situation shaped by cultural values, goals, expectations, and concerns (Cai et al., 2021). Research consistently demonstrates a positive link between physical activity and quality of life (Gavala-González et al., 2022). Notably, participation in sports, a specific type of physical activity, offers distinct advantages for both physical and psychological health, as well as social outcomes in adults (Eather et al., 2023). Several instruments exist for measuring quality of life, such as the Quality-of-Life Scale (Flanagan, 1978), the McGill Quality of Life questionnaire – the World Health Organization Quality of Life Instrument (WHO, 2012), the Health-Related Quality of Life Questionnaire (Centers for Disease Control and Prevention [CDC], 2000), and Expanded (Cohen et al., 2019).\n\nTable tennis emerged as a unique and accessible sport for people of all ages, particularly seniors. Compared to other sports, it offered a lower risk of injury, making it suitable for individuals with joint limitations (Killerspin, 2024). Table tennis also provided benefits for youth in various aspects, considering the social ecology, including individual factors, social support networks, and the physical environment where the game is played (Xiao et al., 2020). Additionally, table tennis was relatively inexpensive, required minimal space, and could be played throughout one’s lifespan, making it an attractive option for many (Sportanddev, 2021).\n\nSeveral studies explored the positive effects of table tennis across different age groups. Research by Naderi et al. (2018) suggested that regular table tennis training improved lipid profiles and body composition in aging men. Similarly, Pradas et al. (2021) found that children playing table tennis regularly for two years exhibited better physical fitness and the development of bone, compared to those who didn’t regularly play. The benefits extended beyond physical health. Deprá et al. (2022) demonstrated that a twice-weekly table tennis program could improve agility and balance in physically active seniors. Finally, Olsson et al. (2020) showed that table tennis training was safe and feasible for individuals with Parkinson’s disease, potentially improving balance, well-being, and self-reported physical activity levels.\n\nThis study investigates the quality of life of senior table tennis players in Thailand, particularly focusing on the association between quality-of-life aspects and players characteristics.\n\n\n\n1. To assess the senior Table tennis players’ quality of life in Thailand\n\n2. To study the association of the quality-of-life domains and its players characteristics\n\n\nMethods\n\nThis study utilized a quantitative approach. The quantitative analysis involved using descriptive statistics and Pearson correlation to analyze the data collected from 136 table tennis players who participated in the Thailand Master Table Tennis Championships 2024. The questionnaire used for data collection was based on the WHOQOL measurement of quality of life, which consisted of four dimensions: Physical Health, Psychological Health, Social Relationship, and Environmental Health. The instrument used a five-point Likert scale and was measured using five items. The Pearson correlation coefficients were calculated between the scores of the quality of life in the four dimensions and the overall score, revealing significant correlations (p < 0.01) with all dimensions, including physical health, psychological health, social relationships, and environmental health. The quantitative analysis involved both descriptive statistics to describe the characteristics of the participants and Pearson correlation to examine the relationships between quality-of-life dimensions and overall score. Examples of items include: “How satisfied are you with your current health?” and “How satisfied are you with your sleep quality” (To-aj Oam et al., 2024). This research was ethically approved on 30th November 2023 by the Office of the Committee for Research Ethics (Social Sciences), Faculty of Social Sciences and Humanities, Mahidol University and the approval number is 2023/205.3011. Written consent was obtained from all participants involved in this study. They were clearly instructed about the project and informed that the collected data would be used for publishing the findings. Participants were also given the opportunity to withdraw from the study at any time. However, none of the participants chose to withdraw and they continued until the completion of the study.\n\nThe participants were all Table tennis players (136 Table tennis players) those who registered for attending in the Thailand Master Table tennis Championships 2024 which hosted in January 2024 at Chiang Mai, Thailand. The three experienced researchers have been trained and practiced for the data collection protocol to ensure the research process quality. All the participants were collected the data before the competition began. Each participant spent about 30 minutes for completing the questionnaire (To-aj, Oam et al., 2024). All the participants were closely assisted by the research assistants regarding to the questionnaire explanation. All questionnaires have been proved by the researchers to confirm all items were answered.\n\nThe questionnaire based on the measurement quality of life, WHOQOL which consisted of 4 dimensions: Physical Health, Psychological Health, Social Relationship, and Environmental Health. The instrument was measured using the five-items of the WHOQOL measured on a five-point Likert scale.\n\nDescriptive statistics, Pearson Correlation by using SPSS version 22 (https://www.ibm.com/spss).\n\n\nResults\n\nThe study found that a majority of respondents were male (61.03%). The average age of participants was 51.56 years, with ages ranging from 40 to 76 years old. The largest group (77.94%) fell within the 40-59 age range. Most respondents (58.82%) held a bachelor’s degree. In terms of employment, the majority (44.85%) were self-employed. Notably, a high proportion (87.50%) reported no history of illness. These details were further presented in Table 1.\n\nThe study investigated the quality of life using the WHOQOL-BREF Thai version. The average scores for the four dimensions were: physical health (26.35), psychological health (23.58), social relationships (11.07), and environmental health (29.32). The overall quality of life score was 97.79, suggesting a good quality of life for the participants. Details were presented in Table 2.\n\nThe analysis of Pearson correlation coefficients between the quality-of-life dimension scores and the overall quality of life score revealed significant correlations (p < 0.01) between overall quality of life and all four dimensions measured by the WHOQOL-BREF Thai version: physical health, psychological health, social relationships, and environmental health. These findings were presented in detail in Table 2.\n\nWhen considering the physical health dimension, it was found to be correlated with the psychological health dimension at a statistically significant level of 0.01. The Pearson correlation coefficient (r) was 0.704, indicating a high level of correlation, and they were a direct variation. When considering the social relationship dimension, it was found to be correlated with the environmental health dimension at a statistically significant level of 0.01. The Pearson correlation coefficient (r) was 0.708, indicating a high level of correlation, and they were also a direct variation. They were displayed in Table 3.\n\nWhen considering the individual factors, the respondents working in private sector needed to be focused on. The study revealed that this group of respondents tend to have higher quality of life levels in the psychological health dimension, ranging from moderate to high, compared to other occupational groups with statistical significance (p <0.001***). The study also revealed that the respondents working in private sector tend to have a moderate level of quality of life in the social relationship dimension compared to other occupational groups. On the other hand, civil servants have a higher level of quality of life in the social relationship dimension compared to other occupational groups with statistical significance (p < 0.023*). Moreover, the same group tend to have a moderate and high level of quality of life in the social relationship dimension compared to other occupational groups with statistical significance (p < 0.038*). All details were demonstrated in Table 4.\n\n* Higher value.\n\nFemales had a higher mean (0.069) than males. The mean (0.052) for the 59 or underage group was higher than the 60 or over age group. The master’s degree or over education group (0.169) had a higher mean than both the Secondary school or under group and the Vocational Degree/Bachelor Degree group (0.469). Business owners and others (0.087) had a higher mean than farmers/civil servants (0.172) and company employees/state enterprise employees. Those with no illness (0.157) had a higher mean than those with illness.\n\n\nDiscussion\n\nThe findings of this study align with researches conducted in the past which were as follows;\n\nThe study found that the most of them were self-employed. It is in line of Groessl et al. Results found that the average cost/participant was $1134 and $175 for the physical activity (PA) (Groessl et al., 2009).\n\nOur analysis using the WHOQOL-BREF Thai version revealed the environmental health dimension had the highest average score (29.32) among the four quality of life dimensions. This aligns with Jolanki (2021) on senior housing fulfilling its promise of providing accessible physical and social environments. These environments encourage residents to be independent, physically active, and participate in social activities, ultimately promoting well-being and healthy aging. Similarly, Stenner et al. (2019) highlighted the continued importance of physical activity for some older adults, potentially contributing to improved health and well-being. It’s important to acknowledge risk factors as well. Seangpraw et al. (2020) identified factors like alcohol consumption and illness as significant stressors for the rural Thai elderly population.\n\nThe study investigated quality of life using the WHOQOL-BREF Thai version. Interestingly, the environmental health dimension had the highest average score (29.32). This finding aligns with Jolanki (2021), which suggested that senior housing that provides accessible physical and social environments can encourage residents to be physically active and independent while fostering social connections and a sense of security. Such an environment demonstrably supports well-being and healthy aging. Similarly, Stenner et al. (2019) found that sport can remain important for some older adults and may contribute to improved health and well-being in later years. Furthermore, Seangpraw et al. (2020) identified risk factors such as alcohol consumption and illness as significantly impacting stress levels among the senior population in rural Thailand.\n\nOur analysis revealed a statistically significant correlation (p < 0.01) between the social relationship and environmental health dimensions. The Pearson correlation coefficient (r) of 0.708 displayed a strong positive correlation, suggesting that these dimensions directly vary together. This finding aligns with research by Jia et al. (2023) who identified a significant correlation between living arrangements, preferred living arrangements, and depression in older adults. Similarly, Pei et al. (2022) demonstrated that living arrangements play a crucial role in indirectly predicting depression through social support. Furthermore, Chen (2019) found that preferred living arrangements reflect needs, cultural norms, and current experiences. Their results support the hypothesis that concordance between preferred and actual living arrangements improves subjective well-being (SWB) in older parents, including reducing depressive symptoms and enhancing happiness.\n\nThe study examined individual factors and found that respondents working in the business owner/other tended to have higher quality of life scores in the psychological health dimension, ranging from moderate to high, compared to other occupational groups. This aligns with research by Dirzyte and Patapas (2022) who found that employees in private sector reported greater support, dignity, forgiveness, care, and positive practices, along with higher optimism scores, compared to public sector employees.\n\n\nConclusions\n\nPlaying Table tennis for senior in the tournament level helped to improve the quality of life in all domains. The results can be applied for those stakeholders that relevant to the Table tennis organizations whether the public or private section which were responsible for supporting the senior in the community to exercise and to compete in the Table tennis tournament. The further study would be able to apply with the different participants such as youth players which the research finding would be the benefit for improving their quality of life.\n\nThis research was ethically approved by the Office of the Committee for Research Ethics (Social Sciences), Faculty of Social Sciences and Humanities, Mahidol University with the approval number 2023/205.3011. The Committee of Research Ethics (Social Sciences) is in full compliance with International Guidelines of Human Resource Protection such as declaration of Helsinki, The Belmont Report, and CIOMS guidelines. Written consent was obtained from all participants involved in this study. They were clearly instructed about the project and informed that the collected data would be used for publishing the findings. Participants were also given the opportunity to withdraw from the study at any time. However, none of the participants chose to withdraw and they continued until the completion of the study.",
"appendix": "Data availability\n\nFigshare- Underlying Data - Table Tennis EN.xlsx, https://doi.org/10.6084/m9.figshare.25780110.v2 (To-aj et al., 2024).\n\nThis project contains following dataset:\n\n• Underlying Data_Table Tennis.xlsx\n\n• Blank copy of questionnaire.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nThe authors would like to express their gratitude to QUVAE Research and Publications for their valuable assistance with the deposition of the raw data to the Figshare repository.\n\n\nReferences\n\nCai T, Verze P, Bjerklund Johansen TE: The Quality of Life Definition: Where Are We Going? Uro. 2021; 1(1): 14–22. Publisher Full Text\n\nCenters for Disease Control and Prevention (CDC): Benefits of Physical Activity. [Internet]. 2024 [cited 2024 April 27]. Reference Source\n\nCenters for Disease Control and Prevention (CDC): Measuring healthy days: Population assessment of health-related quality of life. [Internet] 2000 [cited 2024 Apr 4]. Reference Source\n\nChen T: Living arrangement preferences and realities for senior Chinese: implications for subjective wellbeing. Ageing Soc. 2019; 39(8): 1557–1581. Publisher Full Text\n\nCohen SR, Russell LB, Leis A, et al.: More comprehensively measuring quality of life in life-threatening illness: The McGill Quality of Life Questionnaire–Expanded. BMC Palliat. Care. 2019; 18(92): 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDeprá PP, Lopes WA, de Oliveira GH , et al.: Effects of table tennis practice on balance and physical fitness in the senior. Journal of Physical Education (Maringa). 2022; 33(1): e3360. Publisher Full Text\n\nDirzyte A, Patapas A: Positive Organizational Practices, Life Satisfaction, and Psychological Capital in the Public and Private Sectors. Sustainability. 2022; 14(1): 488. Publisher Full Text\n\nEather N, Wade L, Pankowiak A, et al.: The impact of sports participation on mental health and social outcomes in adults: a systematic review and the ‘Mental Health through Sport’ conceptual model. Syst. Rev. 2023; 12: 102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFlanagan JC: A research approach to improving our quality of life. Am. Psychol. 1978; 33(2): 138–147. Publisher Full Text\n\nGavala-González J, Torres-Perez A, Gálvez-Fernández I, et al.: Lifestyle and Self-Perceived Quality of Life in Sports Students: A Case Study. Int. J. Environ. Res. Public Health. 2022; 19(3): 1598. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGroessl EJ, Kaplan RM, Blair SN, et al.: A cost analysis of a physical activity intervention for older adults. J. Phys. Act. Health. 2009; 6(6): 767–774. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJia Q, Duan Y, Gong R, et al.: Living arrangements and depression of the older adults– evidence from the Chinese longitudinal healthy longevity survey. BMC Public Health. 2023; 23: 1870. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJolanki OH: Senior Housing as a Living Environment That Supports Well-Being in Old Age. Front. Public Health. 2021; 8: 589371. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKillerspin: Health Benefits of Table Tennis.[cited 2024 Mar 13]. Reference Source\n\nNaderi A, Zagatto AM, Akbari F, et al.: Body composition and lipid profile of regular recreational table tennis participants: a cross-sectional study of older adult men. Sport Sci. Health. 2018; 14(2): 265–274. Publisher Full Text\n\nOlsson K, Franzén E, Johansson A: A Pilot Study of the Feasibility and Effects of Table Tennis Training in Parkinson Disease. Arch. Rehabil. Res. Clin. Transl. 2020; 2(3): 100064. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPei Z, Hu F, Qin W, et al.: The relationship between living arrangements and depression among older adults in Shandong, China: The mediating role of social support. Front. Psych. 2022; 13: 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeráčková J, Peráček P: Sport for the Subjective Dimensions of Quality of Life. IntechOpen; 2020. Publisher Full Text\n\nPradas F, Ara I, Toro V, et al.: Benefits of Regular Table Tennis Practice in Body Composition and Physical Fitness Compared to Physically Active Children Aged 10-11 Years. Int. J. Environ. Res. Public Health. 2021; 18(6): 2854. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSeangpraw K, Auttama N, Kumar R, et al.: Stress and associated risk factors among the senior: a cross-sectional study from rural area of Thailand. F1000Res. 2020; 8: 655. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingh B, Olds T, Curtis R, et al.: Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews. Br. J. Sports Med. 2023; 57: 1203–1209. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSportanddev: There is something exceptional about table tennis. [Internet]. 2021 [cited 2024 Mar 13]. Reference Source\n\nStenner B, Buckley J, Mosewich A: Reasons why older adults play sport: A systematic review. J. Sport Health Sci. 2019; 9: 530–541. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTo-aj O, Krajangkantamatr S, Saenkla P, et al.: Underlying Data - Table Tennis EN.xlsx. Dataset. figshare. 2024. Publisher Full Text\n\nWHO: WHOQOL: Measuring Quality of Life.[cited 2024 Mar 11]. Reference Source\n\nWorld Health Organization (WHO): WHOQOL: Measuring Quality of Life. [Internet]. 2024 [cited 2024 Mar 11]. https://www.who.int/tools/WHOQOL\n\nWorld Health Organization (WHO): WHOQOL User Manual.[cited 2024 Apr 4]. Reference Source\n\nXiao Y, Huang W, Lu M, et al.: Social-Ecological Analysis of the Factors Influencing Shanghai Adolescents’ Table Tennis Skills: A Cross-Sectional Study. Front. Psychol. 2020; 11: 1372. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "325061",
"date": "20 Sep 2024",
"name": "Johnny Lo",
"expertise": [
"Reviewer Expertise Applied statistics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. The literature review was good, however, it's not clear how this study contributes to new knowledge as the knowledge gaps are no clearly stated. 2. More information is required regarding the WHOQOL-BREF tool, i.e. how each item and domain is scored, and how the overall score is calculated. Furthermore, I believe the overall score should be rescaled to range between 0 and 100. 3. Statistical analysis to assess the association between the WHOQOL-BREF and demographic variables is missing. If Pearson correlation was used, then this would be incorrect. 4. At the very least, the result of the QoL measures for the senior table tennis players should be compared to the general Thai senior population for context. 5. There are too many repeat statements in the paper. I) The statement \"Pearson correlation coefficients were calculated between the scores of the quality of life in the four dimensions and the overall score\" was present in the Methods (should be removed from here) and the Section 2 of the results; II) Paragraphs 2 and 3 in the first section of the Discussions are virtually the same. III) Ethics and consent are provided in the Methods and the end of the paper. 6. The last paragraph of the Results section needs to be more precise. For example, it is stated that 'Females had a higher mean (0.069) than males', but what's actually higher? Also, where does the value 0.069 come from? 7. The discussion has no direct mentions of table tennis, so it's unclear how table tennis is relevant here and why this sub-population is selected. 8. There is no control group, and hence one cannot conclude that playing table tennis help to improve QoL, as suggested in the authors' conclusion. 9. Lastly I don't believe the content of the paper is substantive enough.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "12614",
"date": "18 Oct 2024",
"name": "Sornpravate Krajangkantamatr",
"role": "Author Response",
"response": "We have made the following improvements to the manuscript: We have clarified how our study contributes to new knowledge by addressing specific gaps in existing research on the quality of life of senior table tennis players in Thailand. Additional information on the scoring of the WHOQOL-BREF tool has been provided, explaining how each item and domain is scored. The statistical analysis using Pearson correlation to assess the association between the WHOQOL-BREF, and demographic variables has been elaborated upon. Table 5 showing the association between the WHOQOL-BREF, and demographic variables has been added, demonstrating the relationship between characteristics and quality of life. The Results section has been revised for enhanced precision in communicating the study findings. Repetitive statements have been removed from the paper. We have acknowledged the suggestion for future research to include a comparative analysis of quality-of-life measures for senior table tennis players with the general Thai senior population"
}
]
},
{
"id": "325064",
"date": "01 Oct 2024",
"name": "Yuqi He",
"expertise": [
"Reviewer Expertise Sports Medicine",
"Sports Biomechanics",
"Musculoskeletal Simulation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript entitled “Axial rotation affects the cognitive characteristics of spatial ability” is encouraging research, but there are several questions which lists below. You can revise this paper more properly. 1. The meaning and application of this research should be further and clearly expressed in the introduction section. It will help readers to understand the function and value of this study. Please further explain why have to do this research and the possible benefit of this research to this field. 2. Physical activity is beneficial to quality of life, physical health and mental health, explain how it can be shown that it was due to the sport of table tennis that led to this result? Therefore I suggest adding some specific data or experimental design to demonstrate the specific effect of table tennis exercise on quality of life enhancement.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12801",
"date": "14 Nov 2024",
"name": "Sornpravate Krajangkantamatr",
"role": "Author Response",
"response": "This manuscript entitled \"The quality of life in Thai senior table tennis players\" is encouraging research, but there are several questions which lists below. You can revise this paper more properly. Comment 1 The meaning and application of this research should be further and clearly expressed in the introduction section. It will help readers to understand the function and value of this study. Please further explain why have to do this research and the possible benefit of this research to this field. Answer 1 The last paragraph of the introduction part was revised to this one; The previous reports indicated the positive impacts to quality of life from playing table tennis. However, they had never been assessed in Thailand. Therefore, this study investigates the quality of life of senior table tennis players in Thailand, particularly focusing on the association between quality-of-life aspects and players characteristics. This analysis will provide deeper information on the effect of competing table tennis and quality of life of senior players in Thailand. Comment 2 Physical activity is beneficial to quality of life, physical health and mental health, explain how it can be shown that it was due to the sport of table tennis that led to this result? Therefore, I suggest adding some specific data or experimental design to demonstrate the specific effect of table tennis exercise on quality-of-life enhancement. Answer 2 These sentences have been added to manuscript; Ishiguro & Amano (2022) showed that playing table tennis offered several health benefits, including better muscle strength, physical performance, body composition, and lipid profiles in recreational table tennis players relative to their age-matched counterparts. Zhang and Min (2022) indicated that the mental health of girls has been changed positively after joining the table tennis exercise. I’ve also added these articles on the reference list as follows; References 12 Ishiguro A., Amano T.: Comparisons of cardiorespiratory and thermoregulatory responses to table tennis and cycling at similar perceived levels of effort. Science and Sports. 2022;37(2):143:e141-143.e149. https://doi.org/10.1016/j.scispo.2021.03.005 29 Zhang Z, Min HJ: Effects of Different Physical Exercises on Physical and Mental Health of Female College Students. Journal of Healthcare Engineering. 2022; 7812005. https://doi.org/10.1155/2022/7812005 Best,"
}
]
}
] | 1
|
https://f1000research.com/articles/13-1064
|
https://f1000research.com/articles/13-470/v1
|
09 May 24
|
{
"type": "Systematic Review",
"title": "The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review",
"authors": [
"Muhamad Taufik Ismail",
"Dyah Wulan Anggrahini",
"Sofia Mubarika Haryana",
"Budi Yuli Setianto",
"Dyah Wulan Anggrahini",
"Sofia Mubarika Haryana",
"Budi Yuli Setianto"
],
"abstract": "Background Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease (PAD) and has poor clinical outcomes. Recently, stimulating arteriogenesis has been proposed to improve clinical outcomes. Several studies have shown that miRNAs have beneficial effects on limb ischemia related to arteriogenesis. This study aimed to review the roles of therapeutic miRNAs in the arteriogenesis of limb ischemia.\n\nMethods A systematic search was conducted through July 2021 using the PubMed, Scopus, and ScienceDirect databases. Two authors independently assessed studies that investigated the role of miRNAs in the arteriogenesis of limb ischemia, both in vivo and in clinical studies.\n\nResults All selected studies were in vivo studies, with a total of 36 articles and 28 types of miRNAs. miRNAs potentially regulate arteriogenesis by targeting different targets. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. MiRNA-126 was the most studied miRNA, and SPRED1 was the most common target of microRNA. However, the included studies showed high heterogeneity in terms of inducing hindlimb ischemia, the timing of administration, and the method used for evaluating arteriogenesis. Moreover, most studies presented unclear or high-risk bias.\n\nConclusion MicroRNA application in a preclinical model of hindlimb ischemia has beneficial effects on arteriogenesis. This result indicates that miRNAs might be potentially beneficial in patients with CLTI.\n\nRegistration The review protocol was registered with PROSPERO under registration number CRD42024484988.",
"keywords": [
"Keywords: microRNA",
"arteriogenesis",
"limb ischemia",
"gene target"
],
"content": "Introduction\n\nChronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease (PAD) due to the blockage of blood vessels.1 Its amputation and mortality rates using a conservative approach are still high at 27% and 18% at 12 months after diagnosis, respectively,2 despite being successfully revascularized.3,4 Patients who present with late-onset and severe degree of tissue damage have the highest risk of amputation.4 Therefore, other therapeutic approaches need to be developed.\n\nGenetic or cellular-based therapeutic approaches have been developed to increase neovascularization in the form of arteriogenesis and angiogenesis.1 Unfortunately, angiogenesis is inadequate for replacing occluded or stenotic arteries. Furthermore, the long distance between the stenotic vessel and tissue hypoperfusion makes it more relevant to arteriogenesis than angiogenesis.5 Therefore, patients with CLTI generally require more arteriogenesis than angiogenesis.6\n\nStudies on stem cell therapy for CLTI in clinical studies recently has not yet shown promising outcome.1 It is possibly due to inability of stem cells in the ischemic condition.6 Similar result occurred with the trials of growth factors administration in CLTI patients.7 The expectation of increase neovascularization to compensate the ischemic limb, comes into a failure due to angiogenic signaling resistance. Therefore, the findings of miRNA signaling might be a solution for repairing the angiogenic signaling pathway or its resistance.8\n\nSeveral miRNAs can improve arteriogenesis through different signaling pathways, either by increasing or inhibiting their expression depending on a specific type of miRNA.8 Arteriogenesis consists of two phases: an early inflammatory phase followed by an increase in blood vessel diameter, remodeling, and vessel maturation. Furthermore, several processes including proliferation of endothelial cells, smooth muscle cells, and remodeling of tunica adventitia are also essential for arteriogenesis.9 MicroRNAs can interfere those processes through gene regulation, since several genes are needed, particularly involved in the proliferation of endothelial cells, smooth muscle cells, activation of adhesion molecules, regulation of extracellular matrix, and regulation of growth factors and their receptors.10 Therefore, this study was aimed to review the role of therapeutic microRNAs in arteriogenesis process of limb ischemia.\n\n\nMethods\n\nThe review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42024484988), however the protocol has yet to be published. We performed this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.\n\nWe searched for basic and clinical studies published in the PubMed, Scopus, and ScienceDirect databases on July 25, 2021. The literature is limited to English. We use the PICO strategy to answer this research question. The following terms were used for the literature search: (peripheral arterial disease OR peripheral artery disease OR chronic limb threatening Ischemia OR critical limb ischemia OR hindlimb Ischemia OR hind-limb ischemia OR femoral artery ligation OR hindlimb) AND (microRNA OR microRNAs OR miRNAs OR “micro RNA” OR miRNA OR “micro RNAs”) AND (angiogenesis OR arteriogenesis OR neovascularization OR collateral).\n\nTwo authors (MT and DA) independently assessed the eligibility of the studies. The inclusion criteria were as follows: 1) Explaining the role of miRNAs in the arteriogenesis process of limb ischemia, either in vivo or clinical studies; 2) if in vivo study, inducing limb ischemia in animal models must be clearly described; 3) articles published in full-text journals; 4) Articles in English; and 5) articles assessing arteriogenesis using imaging or staining methods. The exclusion criteria were as follows: 1) the study involved only an in vitro study, 2) there was no control group in an in vivo study, and 3) the study was not conducted as primary research.\n\nTwo authors independently extracted the data from the included studies (MT and DA). The extracted data included the author’s name, publication year, animal models (type of animal, strain, age, how to induce limb ischemia, concomitant conditions, and if any animal gender was also included), type of microRNA, administration method in intervention and control groups, and techniques for evaluating arteriogenesis, including time points of assessment and outcomes. Any disagreements between the authors were resolved through discussion. Owing to the high heterogeneity of the included studies, a meta-analysis could not be conducted. We developed ‘Characteristics of study’ tables to summarize and compare the data above.\n\nThe risk of bias was evaluated by two authors (MT and DA) using the SYRCLE’s risk of bias tool for animal studies. Disagreements were resolved through discussion.\n\n\nResults\n\nA systematic search of several databases identified 1317 relevant papers for this study (PRISMA Flowchart for The Systematic Review).59 A total of 130 articles remained after removing duplicate publications and screening titles and abstracts. Furthermore, 3 articles with no full text available and 91 studies were not included because there was no analysis of miRNA in arteriogenesis. Therefore, 36 articles with 28 types of miRNAs were eligible for further analysis in this systematic review. The selected articles showed substantial heterogeneity, including animal models, intervention approaches, control groups, timing of administration, and methodology used to assess arteriogenesis.\n\nAll the selected studies in Characteristics of Study (Table 1)59 show that strain, animal models, concomitant conditions, and techniques used to induce limb ischemia varied among studies. Almost all of the studies (n=35, 97,2%) used a rodent as a model, of which 33 studies used mice and 2 studies used rats. BALB/c and C57Bl/6 were the most commonly used mouse strains. The two strains used in this study were Fischer and Adult Sprague-Dawley rats. Furthermore, only one study used New Zealand White rabbits. Regarding concomitant conditions, diabetic mice were used in five studies and immunocompromised mice were used in two studies, 2 studies used hypercholesterolemic mice model, and 1 study used aging mice. Three studies used genetically modified mice compared to wild-type mice to determine the effect of a specific type of microRNA on arteriogenesis. Moreover, the techniques used to create hindlimb ischemia vary widely varied.59\n\n\n\n• let-7g enhanced expression of VEGF-A and VEGFR-2 through targeting HIF-3α and TP53. Moreover, let-7g influenced the splicing factor SC35, which consequently increased the alternative splicing of VEGF-A, from VEGF-A165b (anti-angiogenic isoform) to VEGF-A164a (pro-angiogenic isoform).11\n\n\n\n• Inhibition of miR-15a/16 enhanced arteriogenesis and angiogenesis in a mouse model of limb ischemia.12\n\n• Overexpression of miR-15a or-16 decreased Tie2 at the protein level.13\n\n\n\n• VEGF-A and AKT3\n\n• Tie2\n\n\n\n• Inhibition of miR-329, miR-487b, miR-494, and miR-495 led to arteriogenesis and angiogenesis.10\n\n\n\n• Regulating arteriogenesis and angiogenesis via targeting AKT3/eNOS pathway.14\n\n\n\n• Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) contained miR-21 which repaired neovascularization by increasing the activity of HIF-1α by targeting CHIP.15\n\n\n\n• Downregulation of MiR29a and upregulation of ADAM12 in ischemia with hyperglycemia state was impaired. Knocking down miR29a was adequate for fixing ADAM12 upregulation in ischemia with a hyperglycemia state. Hence, improving perfusion and angiogenesis even when vascular endothelial growth factor signaling was impaired.16\n\n\n\n• Inhibition of miR-92a contributed to enhancing angiogenesis and arteriogenesis.17\n\n\n\n• miR-93 impeded interferon regulatory factor-9 to reduce the production of IRG1–itaconic acid, therefore it stimulated M2-like polarization in ischemic muscle. Consequently, it increased angiogenesis, arteriogenesis, and blood perfusion.18 Another study showed that curcumin improved angiogenesis and arteriogenesis by promoting the expression of miR-93.19\n\n• miR-93 increased arteriogenesis and angiogenesis by regulating the expression of multiple genes that coordinated the pathway of apoptosis and cell proliferation.20\n\n• miR-93 inhibited CDKN1A expression at the mRNA and protein expression levels. Hence, promoting arteriogenesis and angiogenesis.21\n\n\n\n• interferon regulatory factor-9 (IRF9) multiple genes\n\n• Cyclin dependent kinase inhibitor 1A (CDKN1A) gene\n\n\n\n• CD34Exo contained high level of miR-126-3p which enhanced arteriogenesis and angiogenesis by suppressing the expression of SPRED1. Hence, modulating severals genes expression (VEGF, angiopoietin 1, angiopoietin 2, MMP9, thrombospondin 1, etc).24\n\n• The sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) enhanced perfusion and angiogenesis by suppressing the expression of SPRED1.25 Another study showed that miR-126 loaded with Bubble liposomes had the same result.26\n\n• Adipose-Derived Stem Cell Therapeutic Factor Concentrate had a high level of miR-126, which increased perfusion and angiogenesis.27\n\n• MiR-126-3p repaired perfusion and angiogenesis by suppressing the expression of SPRED1 and PIK3R2.28\n\nThe therapeutic and timing of administration varied among the included studies. Intramuscular injection was the most commonly used (n=21), followed by tail vein (n=5), intra-arterial (n=2), oral (n=1), retro-orbital (n=1), and not clearly explained (n=1). Meanwhile, there were 3 studies that did not use therapeutic agents (owing to genetic modification). Regarding the timing of administration, 11 studies performed repeated administration at different time points: 10 studies administered agent immediately after ligation, 2 studies administered drug one day before ligation, one study delivered agent 30 min before ligation, one study administered agent on day 1 after ligation, one study gave agent on day 7 after ligation. Unfortunately, 7 studies did not clearly state when the agent was administered.\n\nThe methods used to evaluate arteriogenesis also varied among the included studies. Imaging techniques were the most commonly used among the studies, from which 31 studies used laser Doppler perfusion imaging, one study used high-resolution laser color Doppler imaging, one study used laser speckle perfusion imaging, one study used contrast-enhanced ultrasound (CEU), one study used periCam perfusion speckle imager, two studies used whole-mount vascular casting, one study used postmortem vascular casting, and one study used postmortem angiogram. Staining methods were also used, and α-smooth muscle actin (α-SMA) staining was the most commonly used method, either by immunohistochemistry or immunofluorescence (n=12). Some of the techniques were combined, of which the most common combination was laser Doppler perfusion imaging and α-smooth muscle actin (α-SMA) staining (n=11). The duration of outcome observation varied among the studies from 7 days to 48 days. The observation time points varied during the observation period.\n\nTable 1 shows that, depending on the specific type of miRNA, some miRNAs need to be upregulated or downregulated to enhance arteriogenesis and vice versa. Some of microRNAs need to be upregulated, namely, miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. In contrast, several microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. Several microRNAs were loaded when administered to hindlimb ischemia models, namely microRNA-126 was naturally contained in CD34Exo and adipose-derived stem cell therapeutic factor concentrate. MicroRNA-939-5p was abundant in exosomes from patients with myocardial ischemia (isc-Exo). Furthermore, microRNA-21 is abundant in umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). Finally, curcumin contained a high level of microRNA-93. Table 1 also shows that miR-126 and miR-93 are the most commonly assessed miRNAs in hindlimb ischemia. Regarding the therapeutic target of microRNAs, SPRED1 was the most common, namely miR-126 and -132/212.\n\nSYRCLE’s risk of bias tool for animal studies was used to assess the risk of bias, and the outcomes are shown in Risk of Bias Assessment.59 In most studies, the risk of bias fell into two categories: “unclear” or “high.” In particular, the majority of studies did not specify the adequacy of the generation and application of the allocation sequence, the concealment of allocation to different groups during the experiment, or the random housing or selection of animals for outcome assessment, whether investigators were blinded to the interventions received by each animal, or whether the outcome assessor was blinded.\n\n\nDiscussion\n\nThis study aimed to systematically search and review the literature on the therapeutic potential of microRNAs in limb ischemia. To date, only in vivo studies have evaluated the potential role of miRNAs in arteriogenesis. Depending on the specific type, the expression could lead to enhanced or decreased arteriogenesis. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. These miRNAs have different target sites in arteriogenesis, with miRNA-126 being the most studied (Figure 1). The high heterogeneity among selected studies in terms of microRNA used, techniques for inducing limb ischemia, administration methods in intervention and control groups, and techniques for evaluating arteriogenesis as well as time-points of outcome assessment, hindered the performance of a meta-analysis.\n\nIn this study, mice were the most commonly used limb ischemia models because of their practical aspects and their similarity to humans in terms of neovascularization patterns and genetic aspect.46–48 Moreover the availability of several transgenic mice might be the reason for preferring the use of mice, as shown in these studies. Unfortunately, only two studies were performed in immunocompromised mice, since miRNAs might stimulate immune responses, including macrophages and T cells, and thus might affect the outcome of arteriogenesis.46,49 The technical approach for inducing limb ischemia was also widely varied in this study, which might affect the arteriogenesis outcome. Double ligation of the iliac and femoral arteries causes severe ischemia rather than single ligation. Moreover, the ligation approach is better than electrocoagulation since recoil will not occur.46 Concurrent ligation and excision methods will increase the severity level of ischemia.50 Regarding to sex animal models, most of the selected studies used male due to hinder the effects of estrogen on vascular regrowth.51 Unfortunately, several studies did not clearly declare animal sex, and two studies in rabbits and mice used female sex.\n\nImaging techniques can assess arteriogenesis anatomically or functionally.52 In this study, most studies used a functional approach such as laser doppler perfusion imaging which assesses restoration of tissue perfusion, equivalent to the sign of effective arteriogenesis.52 The anatomical approaches used in this study were whole mount vascular casting, postmortem vascular casting, and postmortem angiogram. A combination of anatomical and functional approaches can provide more insight into both the visual and quantitative extent of circulation formation and its functional effectiveness.52 In this study, miR-199a-5p and miR-146 were assessed using both methods. In addition to imaging methods, histological staining has also been used to assess arteriogenesis.53 Unfortunately, none of these studies used a combination of anatomical, functional imaging, and histological staining. Such a combination may yield more reliable results.\n\nIn general, the arteriogenesis process requires endothelial and smooth muscle cell proliferation, in which growth factor is crucial to proliferate smooth muscle cells. In the later process, adventitia remodeling through activation and proliferation of fibroblast caused enlargement of lumen vessels.9 Nevertheless, the exact molecular mechanisms involved in all multifactorial arteriogenesis process is still not fully understood.54 However, recent evidence showed that microRNA is involved in signaling pathways related to arteriogenesis.8 As shown in this study, microRNAs affect several pathways related to arteriogenesis, such as Ras-MAPK, TGF-β1/p21, AKT3/eNOS, and JAK-STAT signaling pathway. Table 1 also shows that miRNAs can lead to arteriogenesis by directly targeting several genes and proteins.\n\nVEGF-A is essential for endothelial proliferation by binding to VEGFR-2 to stimulate intracellular signaling process.55 That evidence is supported in this study, in which promoting mir126 and letting 7 g as well as inhibiting mir 15a/16 activate VEGF, leading to arteriogenesis. Another study showed that an increase in miR-139-5p expression in diabetic mice led to downregulation of VEGF, consequently decreasing arteriogenesis. Moreover, miR-223, 100, and 93 also affect cell proliferation by binding to their respective targets, ultimately affecting arteriogenesis.\n\nMacrophage recruitment is essential for arteriogenesis. Activated macrophages produce TNF-α, growth factor, and chemokines and recruit more monocytes, thereby promoting arteriogenesis.9 Those results were supported by the results of the present study, in which miRNAs 199a-5p, 146a, and 155 had a role in macrophage recruitment. Moreover, macrophage polarization to an anti-inflammatory macrophage type 2 in ischemic muscle, shown by miR-93, is essential during post-ischemic vascular injury and repair, since M2 macrophages are pro-angiogenic.56\n\nIn this study, the delivery approach varied; however, most of them used intramuscular injections. However, all delivery approaches, including tail vein, intravenous injection, oral, retro-orbital, and intra-arterial, showed positive results related to arteriogenesis. These results suggested that miRNAs have systemic effects. Depending on the specific type of microRNA, all studies that used concomitant conditions such as diabetic and hypercholesterolemic mice showed positive results in arteriogenesis. These results might suitably explain the use of microRNAs in humans, since CLTI is strongly associated with cardiovascular risk factors, such as diabetes mellitus and dyslipidemia.57 Aging mice might also be analogous to patients with CLTI due to the increasing number of CLTI in the older population.58\n\nThe application of SYRCLE’s risk of bias tool to assess animal studies revealed a prevalent “unclear” or “high” risk of bias across the majority of cases. These studies exhibited deficiencies in essential aspects, such as the generation and application of allocation sequences, allocation concealment, randomization of housing, selection for outcome assessment, and blinding of investigators and outcome assessors. Therefore, these results should be cautiously interpreted.\n\nOur systematic review had several limitations. First, we reviewed only studies published in English. Second, all research conducted in animal models had high heterogeneity related to inducing hindlimb ischemia, intervention, and outcome assessment methods. Therefore, clinical studies in humans are required to verify the effect of miRNA modulation using mimic and/or inhibitor miRNAs in patients with chronic limb-threatening ischemia.\n\n\nConclusion\n\nTaken together, our review identifies several miRNAs in preclinical models that show potential for therapeutic purposes to enhance arteriogenesis in patients with chronic limb-threatening ischemia. Hence, a study involving patients with chronic limb-threatening ischemia is required.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nFigshare: The Role of Therapeutic MicroRNA in Arteriogenesis Process in Limb Ischemia: A Systematic Review. DOI: https://doi.org/10.6084/m9.figshare.25036163.v3. 59\n\nThis project contains the following extended data:\n\n• PRISMA Flowchart for The Systematic Review\n\n• Table 1. Characteristics of Study\n\n• Risk of Bias Assessment\n\n• Completed PRISMA checklist\n\nData are available under the terms of the Creative Commons Zero CC0.\n\n\nAcknowledgements\n\nWe thank Hariadi, Yohanes William, Tinanda Tarigan, Afif Ramadhan, and Jessica Eve from Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing Gadjah Mada University, Sleman, Indonesia for their technical support, all of whom approved their inclusion.\n\n\nReferences\n\nConte MS, Bradbury AW, Kolh P, et al.: Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur. J. Vasc. Endovasc. Surg. 2019; 58(1): S1–S109.e33. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan Reijen NS , Hensing T, Santema TKB, et al.: Outcomes of conservative treatment in patients with chronic limb threatening ischaemia: A systematic review and meta-analysis. Eur. J. Vasc. Endovasc. Surg. 2021; 62(2): 214–224. 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PubMed Abstract | Publisher Full Text\n\nHeuslein JL, Gorick CM, McDonnell SP, et al.: Exposure of endothelium to biomimetic flow waveforms yields identification of miR-199a-5p as a potent regulator of arteriogenesis. Mol. Ther. Nucleic Acids. 2018; 12: 829–844. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang J, Rao G, Qiu J, et al.: MicroRNA-210 improves perfusion recovery following hindlimb ischemia via suppressing reactive oxygen species. Exp. Ther. Med. 2020; 20(6): 231–236. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShi L, Fisslthaler B, Zippel N, et al.: MicroRNA-223 antagonizes angiogenesis by targeting β1 integrin and preventing growth factor signaling in endothelial cells. Circ. Res. 2013; 113(12): 1320–1330. PubMed Abstract | Publisher Full Text\n\nGuan Y, Cai B, Wu X, et al.: MicroRNA-352 regulates collateral vessel growth induced by elevated fluid shear stress in the rat hind limb. Sci. Rep. 2017; 7(1): 6643. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCaporali A, Meloni M, Völlenkle C, et al.: Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation. 2011 January 25; 123(3): 282–291. PubMed Abstract | Publisher Full Text\n\nIcli B, Wu W, Ozdemir D, et al.: MicroRNA-615-5p regulates angiogenesis and tissue repair by targeting Akt/eNOS (protein kinase B/endothelial nitric oxide synthase) signaling in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2019; 39(7): 1458–1474. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHan C, Zhou J, Liu B, et al.: Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb. Mater. Sci. Eng. C. 2019; 99: 322–332. 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PubMed Abstract | Publisher Full Text\n\nIsmail MT, Anggrahini DA Haryana SM, Setianto BY: Data from: The role of therapeutic microRNA in arteriogenesis process in limb ischemia: A systematic review. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "326630",
"date": "29 Oct 2024",
"name": "Brian H Annex",
"expertise": [
"Reviewer Expertise Human and experimental peripheral arterial disease including but not limited to non-coding RNAs."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript by Asmail et al. is a systematic/literature review of micro-RNA reported to be related to peripheral arterial disease. In general, the limitations of such reviews are well known but the benefits are in providing a single go-to source of information. Before this reviewer lists a series of relatively minor comments/areas that require clarification, one request for additional (new) data will be listed.\n1) Often in a study that focuses on a microRNA, other microRNAs are also examined. If a publication focused on miR-A (letter intentionally used to avoid confusion) were other miRs that ultimately ended in this report also studied? For example, if in the study of miR-A, miR-B and miR-C (where miR-B and miR-C ultimately made this report) were also found to differentially regulated, that would provide a validation. If several reports of course even better. It of course could turn out that study of the regulation miR-B in teh report on miR-A could be different. That would be valuable as well. Likely, in many, this may not be possible but this could expand the value of the review.\nMore minor comments: 1) Introduction, paragraph 2, last sentence. Given that no agent has definitely driven angiogiogenesis in CLTI, this sentence may not be completely accurate.\n\nTo make the statement one would need an agent that promoted angiogenesis, not arteriogenesis, and had no therapeuitc effect.\n2) Introduction, paragraph 3, miRs do not signal unless the authors are referring to miR-protein interactions.\n3) Methods, when the two \"selectors\" disagreed initially on inclusion -- how often was the agreement for and how often against inclusion.\n4) Curcumin was mentioned. Was this referring to the dietary supplement? Would a miR be stable through the GI track?\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No",
"responses": [
{
"c_id": "12807",
"date": "14 Nov 2024",
"name": "Muhamad Taufik Ismail",
"role": "Author Response",
"response": "Dear Brian H Annex, thank you for your time and insightful comments. In our study, of the 36 studies reviewed, 35 directly employed specific miRs or agents containing/enriched with/affecting specific miRs, and therefore did not assess other miRs. One study by Li did examine additional miRs using microarray technology; however, only the miRs with a significant role in arteriogenesis were reported. Some studies validate each other due to shared regulatory pathways, such as with miR-93 and miR-126. No studies presented conflicting findings. Here is the response for addressing minor comments: 1. Our aim was to emphasize the general importance of arteriogenesis over angiogenesis in CLTI, as highlighted by Caicedo et al. According to the 2019 ESVS guidelines on CLTI, agents such as stem cells have been shown in clinical trials to enhance angiogenesis, however, they have yet to yield clinical benefits in terms of reducing amputation rates or mortality. This finding underscores the need to prioritize arteriogenesis rather than angiogenesis in this context. 2. We sincerely appreciate your insightful comments and suggestions for revising the paper. We have revised the sentence to clarify the role of miRNAs in influencing signaling pathways rather than directly \"signaling.\" This revision aims to reflect the regulatory role of miRNAs in modulating pathway activity without implying direct signaling. 3. Thank you for your question. In cases where the two reviewers (MT and DA) initially disagreed on inclusion, an additional review by senior reviewers (BY and SM) was conducted to reach a consensus. In 80% of the journals, both reviewers shared the same inclusion criteria, while in 20% of cases, differing opinions required a final decision from the senior reviewers. 4. Based on the article, curcumin is categorized as a dietary supplement because it is a naturally occurring compound derived from turmeric and was administered orally, similar to the typical consumption of dietary supplements. In this study, curcumin is used to investigate its therapeutic effects, showing that while curcumin does not contain miRNAs necessary for arteriogenesis, it modulates the expression of endogenous miRNAs to impact molecular pathways, specifically targeting miRNA pathways within cells. I will incorporate these points in revising the manuscript. It is well-established that many naked miRNAs degrade in the gastrointestinal (GI) tract due to exposure to enzymes, stomach acidity, and intestinal nucleases."
}
]
}
] | 1
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https://f1000research.com/articles/13-470
|
https://f1000research.com/articles/12-1554/v1
|
04 Dec 23
|
{
"type": "Research Article",
"title": "Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study",
"authors": [
"Yasser K. Al-Rubiay",
"Najah K. Mohammad",
"Najah K. Mohammad"
],
"abstract": "Background: Central serous chorioretinopathy (CSCR) is a common retinal condition with an increased risk of recurrence. Traditional approaches have made choroidal visualization challenging, but recent advances in optical coherence tomography (OCT) innovation have permitted the collection of more accurate choroidal visualizations. This study aimed to measure choroidal thickness in eyes with active CSCR as well as in the unaffected opposite eyes of these same individuals. Methods: This research was conducted at the ophthalmology division in Ghazi Al-Hariri hospital from the 1st of October 2019 until the 31th of March 2020. A total of 49 people, corresponding to 65 eyes, were included in the study. Among these participants, 16 individuals presented with central serous chorioretinopathy (CSCR), affecting a total of 32 eyes. The CSCR individuals were further split into two groups: \"group A\" consisted of 20 eyes with active CSCR, and \"group B\" encompassed the remaining 12 unaffected opposite eyes. Additionally, 33 individuals who were age and gender-matched served as controls assigned as \"group C\". Results: The choroid exhibited a substantial rise in thickness across each of the nine sectors in group A as compared to group C. Similarly, group B showed a significant increase in choroidal thickness in relation to group C. The mean subfoveal choroidal thickness (SFCT) was measured as follows: 474.55μm, 437.5μm, and 292.03μm among groups A, B, and C, correspondingly. These differences were identified as clinically significant for both A vs. C and B vs. C. Conclusions: This study's findings indicate a thickening of the choroid in both eyes exhibiting active CSCR, as well as in the unaffected opposite eyes of those with the disease.",
"keywords": [
"Central Serous Chorioretinopathy",
"Choroidal Thickness",
"Swept Source Optical Coherence Tomography",
"Retina",
"Ophthalmology"
],
"content": "Introduction\n\nCentral serous chorioretinopathy (CSCR) typically affects men of working age, according to Kitzmann et al. (2008).1 The estimated incidence rate for males is 10 cases per 100,000, while for women it is 2 cases per 100,000.2 The presence of neuroretinal separation, produced by the buildup of serous subretinal fluid (SRF), distinguishes clinical central serous chorioretinopathy.3 This buildup is caused by a malfunctioning retinal pigment epithelium (RPE), as well as increased permeability and thickness of the underlying choroid. The condition is characterized by the degradation of central vision, the existence of a central scotoma, and the presence of micropsia or metamorphopsia.4 CSCR is a retinal disorder that can be identifiable by the separation of the neurosensory layer of the retina.5 The disease is commonly categorized into two types: acute central serous chorioretinopathy, which usually heals on its own around a period of 4 months, and chronic CSCR.6 The categorization of these types is determined by the duration it takes for the subretinal fluid to subside.7 At present, a definitive consensus regarding the precise period differentiating the acute and chronic forms is lacking.8\n\nIn a previous study, the occurrence of both side’s appearance was estimated to be 14%,9 while a different study disclosed it to be 34%.10 This variation can be attributed, in particular, because of the lack of a standardized clinical categorization system for central serous chorioretinopathy among experienced retina professionals.11\n\nThe etiology of central serous chorioretinopathy remains incompletely elucidated. Over the past several decades, there has been a transition concerning previous theories that primarily emphasized the involvement of retinal pigment epithelium (RPE),12 either by the occurrence of localized RPE leaks or a reverse of RPE cell polarity leading to the release of fluid to the subretinal space.13 More recent hypotheses have emerged, highlighting the choroid’s significance in the etiology of CSCR.14\n\nIndocyanine green angiography (ICGA) research studies have demonstrated the presence of extensive and multifocal regions of choroidal hyperpermeability surrounding active retinal pigment epithelium leaking.15\n\nLiu et al. conducted a comprehensive review and meta-analysis, which yielded findings suggesting that several factors, including elevated blood pressure, infection with Helicobacter pylori, steroid medication consumption, sleeping disorder, immune-mediated illness, psychopharmacologic intake, and Type-A personality, may be associated with an increased risk of developing central serous chorioretinopathy.16 A recent study conducted by Jia Yu et al. has established a correlation between various factors, including being pregnant, obstructive sleep apnea, transplantation of organs, kidney failure, and a history of methylenedioxymethamphetamine (MDMA), commonly referred to as ecstasy addiction, and the development of the illness as mentioned earlier.17\n\nIt is hypothesized that an elevation in choroidal vascular permeability may result from arterial vascular spasm induced by adrenaline, which is further intensified by the presence of steroid hormones.18 This process eventually results in choroidal ischemia and a rise in vascular hyper-permeability. Consequently, the level of oncotic pressure within the choroidal space rises, and when paired with the malfunction of the retinal pigment epithelium, the fluid accumulates in the sub-retinal space.19\n\nThe objective of this study is to assess the choroidal thickness in eyes exhibiting active central serous chorioretinopathy along with comparing it with the uninfluenced opposite eyes of the exact same participants, as well as with the regards of a control group consisting of healthy individuals.\n\n\nMethods\n\nOn May 1, 2019, the research proposal, assigned to Research No. 24 and Approval No. 119, was granted approval by the research ethics committee of the Iraqi Board of Ophthalmology. Following a thorough discussion of the study objectives, every participant officially provided written informed consent. The personal information of individuals involved in the study was maintained anonymously.\n\nThe present research was an observational case-control study carried out on a group of Iraqi individuals who were looking for medical care at the retina clinic, which is a part of the ophthalmology division at Ghazi Al-Hariri Hospital for Surgical Specialties within the Medical City Complex in Baghdad, Iraq. The data collection period for this study ran from October 1, 2019, to March 31, 2020. At the completion of the data acquisition process, 49 individuals were successfully included, resulting in a sample size of 65 eyes.\n\nThe recruited cases consisted of confirmed cases of active central serous chorioretinopathy, which is defined as the presence of subretinal fluid on swept-source OCT imaging. A time frame of six months from the onset of signs was determined as the threshold for distinguishing between acute and chronic central serous chorioretinopathy cases.\n\nAny patient presenting with one or more of the following conditions was excluded from the study, refractive errors characterized by a spherical equivalent exceeding 1 diopter, hypertension that is not under control characterized by elevated systolic blood pressure exceeding 139 mmHg and/or alternatively, diastolic blood pressure exceeding 89 mmHg, the patient has a history of receiving intravitreal injections of anti-vascular endothelial growth factor agents, the patient has a history of prior intraocular surgery, the presence of cataracts and media opacities can lead to a decline in image quality, a preceding photodynamic therapy, glaucoma, diabetes type 1 or 2, the history of uveitis or trauma.\n\nThe determination and computation of the sample size were conducted using the software application G*Power 3.1.9.7 (RRID: SCR 013726). The minimum sample size observed in this study was 42 individuals. The effect size was determined to be 0.5, with a power of 95% at a two-tailed alpha level of 0.05. Additionally, a 95% confidence interval was calculated for the observed effect size. A total of 49 participants were chosen for the study, while the remaining individuals met the criteria for exclusion as presented in Figure 1.\n\nGroup A consisted of 20 eyes diagnosed with active central serous chorioretinopathy. It is worth noting that four individuals in this set had both sides of active disease, resulting in the inclusion of each of their retinas in the analysis.\n\nGroup B comprised 12 contralateral unaffected eyes belonging to patients with active central serous chorioretinopathy.\n\nGroup C comprised 33 eyes that were included in the study as healthy controls.\n\nOne of the most successful techniques used by researchers to mitigate sampling bias is simple random sampling, when samples are selected purely based on chance. This research ensured that each member of the population had an equal probability of being selected as a participant.\n\nDuring the study period, individuals who had been diagnosed with central serous chorioretinopathy were recruited from a specialized medical retina clinic. These patients had already undergone fundus fluorescein angiography and provided informed consent. Subsequently, they were referred to the assessment unit, where they underwent a thorough evaluation conducted by a specialized ophthalmologist. The participants were paired according to their ages and sex. The control group was comprised of people who were chosen from the population of family members accompanying patients to the ophthalmology department for problems that were not connected to central serous chorioretinopathy. The procedure included the collection of patient medical records by direct interaction and the performance of a comprehensive examination while the patient was sitting. In order to minimize any diurnal variations in choroidal thickness, all measurements were performed only in the morning, precisely between the hours of 9:00 AM and 12:00 PM. The procedures conducted in this study encompassed various components, including interviews pertaining to the aforementioned aspects. Additionally, a sequential approach was followed for the measurements, commencing with the assessment of visual acuity using a Snellen chart. Subsequently, refraction was determined using an autorefractor, followed by the measurement of intraocular pressure (IOPA) utilizing an air puff tonometer. Furthermore, an evaluation of the anterior segment was performed, and subsequently, one drop of 1% Tropicamide was administered to induce pupil dilation. This facilitated the examination of the posterior segments of the eye using a slit lamp and a +78 diopter condensing lens. Moreover, images of the fundus were captured employing a fundus camera. Additionally, the participant’s height and weight were recorded to facilitate the calculation of their body mass index (BMI). Lastly, arterial pressure was measured in a seated position utilizing a mercury sphygmomanometer. The assessment of choroidal thickness was conducted using the deep-range imaging swept-source optical coherence tomography (SS-OCT) equipment developed by Topcon Corp. in Tokyo, Japan utilizing the default configurations. Each assessment was done by a single trained person using the provided software (version 10.0x). The results were shown using an Early Treatment Diabetic Retinopathy Study (ETDRS) graphic. The measurement of choroidal thickness was conducted in nine distinct sectors located inside the posterior pole, as seen in Figure 2. A summary of the equipment used during the study has been included in Table 1.\n\nThe inner circle has a diameter of 1 mm, the middle circle has a diameter of 3 mm, and the outer circle has a diameter of 6 mm (TOM: temporal outer macula, SOM: superior outer macula, NOM: nasal outer macula, IOM: inferior outer macula, TIM: temporal inner macula, SIM: superior inner macula, NIM: nasal inner macula, IIM: inferior inner macula, SFCT: sub foveal choroidal thickness).\n\nThe statistical process was conducted with SPSS version 23 (RRID:SCR_002865). All data were presented as mean±standard deviation. We employed the independent samples t-test and Fisher’s exact test for analyzing demographic information among our various study groups. To assess the differences in choroidal thickness throughout the study groups, we utilized the Kruskal-Wallis test with Dunn-Bonferroni pairwise comparisons. Significance levels were set at p<0.05 and p<0.001, denoting statistical significance and high statistical significance, respectively.\n\n\nResults\n\nThe current research study included a total of 49 individuals, corresponding to 65 eyes.20 Among these participants, there were 16 individuals diagnosed with central serous chorioretinopathy, accounting for 32 eyes. More precisely, eight participants had acute type, while the remaining eight were chronic cases. The average age of the patients was 38.38 years, with 14 males and two females included in this group. Additionally, there were 33 healthy subjects included in the study, with only one eye per subject being analyzed, resulting in a total of 33 eyes serving as a control group. The average age of the healthy participants was 36.36 years, with 28 males and five females included in this group. The best-corrected visual acuity (BCVA) observed among individuals with central serous chorioretinopathy varied from 6/6 to 6/24, whereas the whole group of control subjects exhibited a BCVA of 6/6.\n\nTable 2 demonstrates that there were no statistically significant differences observed among patients with central serous chorioretinopathy and the control group in terms of age, sex, body mass index, or spherical equivalent.\n\n* Independent samples T-test.\n\n** Fisher’s Exact Test.\n\nIn statistical terms, significant disparities in choroidal thicknesses were observed across every sector whenever comparing group A to group C, and also when comparing group B to group C, despite controlling for variables such as age, sex, body mass index, and spherical equivalent. Furthermore, the choroid exhibited greater thickness in all sectors within group A compared to group B, although this discrepancy did not reach statistical significance, as can be seen in Table 3.\n\n* Kruskal-Walli’s test with Dunn-Bonferroni pairwise comparisons, P-values: group A vs group C/group B vs group C.\n\n\nDiscussion\n\nThe evaluation of the choroid has historically posed difficulties when using conventional imaging methods, such as indocyanine green angiography and B-scan ultrasound imaging. Nevertheless, the advent of optical coherence tomography has enabled the in vivo visualization of the choroid in a manner comparable to retinal imaging, thus providing a more comprehensive inspection.21 Estimating choroidal thickness has presented novel opportunities for investigating various pathologies affecting the choroid.22 One limitation of SD-OCT is its inability to effectively image the sclera-choroidal junction within some eyes, particularly in individuals with media opacities. In contrast, SS-OCT enables the clear imaging of both the retina and the sclera-choroidal junction in such cases.23\n\nThe current research revealed a substantial rise in choroidal thickness throughout all evaluated eye regions exhibiting active central serous chorioretinopathy. Specifically, the subfoveal choroidal thickness was determined to be 474.55 μm in CSCR eyes, whereas it was 292.03 μm in the control group. These findings align with previous investigations utilizing indocyanine green angiography, demonstrating choroidal vessel congestion and heightened permeability of vascular walls (as evidenced by raised choroidal thickness) in CSCR cases.15,24\n\nJirarattanasopa et al. disclosed comparable findings, indicating that the subfoveal choroidal thickness measured 374.3 μm, whereas healthy eyes exhibited an average value of 248.4 μm. It is worth noting that their study employed a prototype swept-source optical coherence tomography device and using traditional measurement techniques, which may account for the observed disparities in comparison to our own measures.25\n\nIn a research project conducted by Cano-Hidalgo et al. in Mexico, it was noted the fact that the average choroidal thickness in the influenced eyes was measured to be 435 μm, similar to the aforementioned study, measurements performed by hand were employed, and the study participants consisted of an older patient group with an average age of 44.23 years±11.57 years. Furthermore, the researchers observed a negative correlation between choroidal thickness and age among patients with central serous chorioretinopathy.26\n\nThe findings of this study indicate that the choroidal thickness in the unaffected eyes of individuals with central serous chorioretinopathy was noticeably greater compared to that observed in control eyes. Specifically, the subfoveal choroidal thickness measured 437.55 μm in CSCR patients’ unaffected eyes, while it measured 292.03 μm in control eyes. This finding was also corroborated by Cano-Hidalgo et al., as well as by other studies utilizing enhanced depth imaging optical coherence tomography.27,28\n\nNumerous studies have demonstrated that eyes afflicted with active central serous chorioretinopathy exhibit a greater thickness of the choroid in comparison to their unaffected counterpart eyes.26,28 The present study yielded comparable findings; however, it did not attain statistical significance, potentially attributable to the limited size of the sample.\n\nThe observed elevation in choroidal thickness in the unaffected fellow eyes implies that the disorder under investigation may have systemic implications, particularly regarding the malfunction of the choroidal vasculature due to abnormalities in the mineralocorticoid receptor pathway among affected individuals.14 This hypothesis is further reinforced by the identified risk factors for central serous chorioretinopathy, including sex, anxieties, steroid consumption, and pregnancy, as well as the susceptibility of choroidal vessels to systemic factors due to their lack of autoregulation.\n\nA number of the limitations that accompany this study pertain to the relatively small sample size employed, which hindered our ability to conduct a comparative analysis of choroidal thickness between acute and chronic central serous chorioretinopathy.\n\n\nConclusion\n\nThe findings of the present research indicate that the choroid exhibits thickening not solely in eyes displaying active central serous chorioretinopathy, but also in the unaffected contra lateral eyes of the same individuals. It is recommended that future research endeavors employ a greater number of participants in order to conduct further investigations utilizing fluorescein angiography as a means to establish associations between choroidal thickness and angiographic findings.",
"appendix": "Data availability\n\nZenodo: Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study. https://doi.org/10.5281/zenodo.8174730. 20\n\nThis project contained the following underlying data:\n\n• Full data.xlsx (Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nKitzmann AS, Pulido JS, Diehl NN, et al.: The Incidence of Central Serous Chorioretinopathy in Olmsted County, Minnesota, 1980–2002. Ophthalmology. 2008; 115(1): 169–173. PubMed Abstract | Publisher Full Text\n\nLotery A: Can we classify central serous chorioretinopathy better? Yes we can. Eye. 2022; 36(3): 487. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMohabati D, Boon CJF, Yzer S: Risk of recurrence and transition to chronic disease in acute central serous chorioretinopathy. Clin. Ophthalmol. 2020; 14: 1165–1175. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaye R, Chandra S, Sheth J, et al.: Central serous chorioretinopathy: an update on risk factors, pathophysiology and imaging modalities. Prog. Retin. Eye Res. 2020; 79: 100865. PubMed Abstract | Publisher Full Text\n\nLee L-C, Wu T-J, Huang K-H, et al.: Increased risk for central serous chorioretinopathy in nephrotic syndrome patients: A population-based cohort study. J. Chin. Med. Assoc. 2021; 84(11): 1060–1069. PubMed Abstract | Publisher Full Text\n\nVan Rijssen TJ, Van Dijk EH, Yzer S, et al.: Central serous chorioretinopathy: towards an evidence-based treatment guideline. Prog. Retin. Eye Res. 2019; 73: 100770. PubMed Abstract | Publisher Full Text\n\nAltun A, Atmaca F, Icagasioglu A, et al.: Central Serous Chorioretinopathy And Selective Serotonin Reuptake Inhibitors.2020.\n\nJoo J-H, Choi JH, Moon SW: Usefulness of Fast Oscillation Electrooculography in Chronic Central Serous Chorioretinopathy. J. Retin. 2020; 5(2): 149–156. Publisher Full Text\n\nGilbert CM, Owens SL, Smith PD, et al.: Long-term follow-up of central serous chorioretinopathy. Br. J. Ophthalmol. 1984; 68(11): 815–820. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJamil AZ, Mirza KA, Qazi ZUA, et al.: Features of central serous chorioretinopathy presenting at a tertiary care hospital in Lahore. J. Pak. Med. Assoc. 2013; 63(4): 478–482. PubMed Abstract\n\nSingh SR, Matet A, Van Dijk EHC, et al.: Discrepancy in current central serous chorioretinopathy classification. Br. J. Ophthalmol. 2019; 103(6): 737–742. Publisher Full Text\n\nMarmor MF: New hypotheses on the pathogenesis and treatment of serous retinal detachment. Graefes Arch. Clin. Exp. Ophthalmol. 1988; 226(6): 548–552. PubMed Abstract | Publisher Full Text\n\nSpitznas M: Pathogenesis of central serous retinopathy: a new working hypothesis. Graefes Arch. Clin. Exp. Ophthalmol. 1986; 224: 321–324. PubMed Abstract | Publisher Full Text\n\nDaruich A, Matet A, Dirani A, et al.: Central serous chorioretinopathy: recent findings and new physiopathology hypothesis. Prog. Retin. Eye Res. 2015; 48: 82–118. PubMed Abstract | Publisher Full Text\n\nGemenetzi M, De Salvo G, Lotery AJ: Central serous chorioretinopathy: an update on pathogenesis and treatment. Eye. 2010; 24(12): 1743–1756. Publisher Full Text\n\nLiu B, Deng T, Zhang J: RISK FACTORS FOR CENTRAL SEROUS CHORIORETINOPATHY: A Systematic Review and Meta-Analysis. Retina. 2016; 36(1): 9–19. Publisher Full Text\n\nYu J, Xu G, Chang Q, et al.: Risk factors for persistent or recurrent central serous chorioretinopathy. J. Ophthalmol. 2019; 2019: 1–6. Publisher Full Text\n\nJampol LM, Weinreb R, Yannuzzi L: Involvement of corticosteroids and catecholamines in the pathogenesis of central serous chorioretinopathy: a rationale for new treatment strategies. Ophthalmology. 2002; 109(10): 1765–1766. PubMed Abstract | Publisher Full Text\n\nPrünte C, Flammer J: Choroidal capillary and venous congestion in central serous chorioretinopathy. Am J. Ophthalmol. 1996; 121(1): 26–34. PubMed Abstract | Publisher Full Text\n\nAl-Rubiay YK: Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study.2023. Publisher Full Text\n\nMontero JA, Ruiz-Moreno JM: Optical coherence tomography characterisation of idiopathic central serous chorioretinopathy. Br. J. Ophthalmol. 2005; 89(5): 562–564. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSezer T, Altınışık M, Koytak İA, et al.: The choroid and optical coherence tomography. Turk. J. Ophthalmol. 2016; 46(1): 30–37. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlibhai A, Or C, Witkin A: Swept Source Optical Coherence Tomography: a Review. Curr. Ophthalmol. Rep. 2018; 6: 7–16. Publisher Full Text\n\nPiccolino FC, Borgia L, Zinicola E, et al.: Indocyanine green angiographic findings in central serous chorioretinopathy. Eye. 1995; 9(3): 324–332. Publisher Full Text\n\nJirarattanasopa P, Ooto S, Tsujikawa A, et al.: Assessment of macular choroidal thickness by optical coherence tomography and angiographic changes in central serous chorioretinopathy. Ophthalmology. 2012; 119(8): 1666–1678. Publisher Full Text\n\nCano-Hidalgo RA, Urrea-Victoria T: Pachychoroid as a biomarker using optical coherence tomography–swept-source in central serous choroidopathy. Latin Am. J. Ophthalmol. 2019; 2: 3. Publisher Full Text\n\nImamura Y, Fujiwara T, Margolis RON, et al.: Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009; 29(10): 1469–1473. Publisher Full Text\n\nKim YT, Kang SW, Bai KH: Choroidal thickness in both eyes of patients with unilaterally active central serous chorioretinopathy. Eye. 2011; 25(12): 1635–1640. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "245534",
"date": "24 Feb 2024",
"name": "Punita K. Sodhi",
"expertise": [
"Reviewer Expertise I have sufficient experience in central serous chorio-retinopathy and have also published and presented work in this field."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1) The division of subjects between three groups should be clearly described. The distribution of subjects among three groups is not clear.\n2) The inclusion criteria is not right, as all subjects with sub-retinal fluid do not have CSCR. The language needs considerable improvement. Study design is not clear. Exclusion criteria generally exclude subjects who have refractive error of about 3 D. 3) The details of methods are not so clear, for example division of subjects among three groups is not clear. 4) For statistical part, a qualified statistician is required to be consulted.\n5) The conclusion that affected individuals and fellow unaffected eyes of affected individuals have thicker choroid is supported with results.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12768",
"date": "14 Nov 2024",
"name": "Yasser K. Al-Rubiay",
"role": "Author Response",
"response": "Dear Colleague I'm greatly thankful for your effort in reading and reviewing my article, I agree with most of the changes you have suggested and I've made these changes and resubmitted the article, kindly find individual responses to your queries: 1) The division of subjects between three groups should be clearly described. The distribution of subjects among the three groups is not clear. This was re-written to be more clear The total patients included were 49, 16 patients with CSCR, 33 controls Of the 16 patients, 4 had bilateral active CSCR, and 12 had unilateral. Groups Group A 20 eyes active CSCR Group B 12 eyes contralateral unaffected eyes of CSCR patients. Group C 33 Right eyes of healthy individuals as controls. 2) The inclusion criteria is not right, as all subjects with sub-retinal fluid do not have CSCR. The language needs considerable improvement. The study design is not clear. Exclusion criteria generally exclude subjects who have a refractive error of about 3 D. We didn’t only use subretinal fluid on OCT as a marker for diagnosis, clinical examination and FFA was used id necessary as per the diagnosing consultant, the study design will be explained better, we selected 1 diopter cut-off value to minimize the effects, this has affected the sample size, and will be mentioned as a study limitation. 3) The details of methods are not so clear, for example division of subjects among three groups is not clear. This is re written to be more clear. The total patients included were 49, 16 patients with CSCR, 33 controls Form the 16 patients, 4 had bilateral active CSCR, 12 had unilateral. Groups Group A 20 eyes active CSCR Group B 12 eyes contralateral unaffected eyes of CSCR patients. Group C 33 Right eyes of healthy individuals as controls. 4) For the statistical part, a qualified statistician is required to be consulted.? The statistics of this study were already done by a doctor with great experience in statistics 5) The conclusion that affected individuals and fellow unaffected eyes of affected individuals have thicker choroid is supported with results.? The conclusion has been re written to make it more understandable."
}
]
},
{
"id": "245535",
"date": "14 Mar 2024",
"name": "Weihua Yang",
"expertise": [
"Reviewer Expertise ophthalmology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe innovative aspect of this study should be explicitly highlighted. For instance, detailing any novel methodological approaches, specific advancements in OCT technology, or unique aspects of the study population that set it apart from previous work would enhance the understanding of its contribution to the field. The statement, \"Group C comprised 33 eyes that were included in the study as healthy controls,\" does not specify which eyes from the control group were included. Clarity is needed on whether both eyes of each control participant were considered or if only one eye was randomly selected for inclusion in the study. The study's comparison between \"group A\" (eyes with active CSCR) and \"group B\" (unaffected opposite eyes) is crucial for understanding the bilateral effects of CSCR. The statistical comparisons between these two groups (A vs. C and B vs. C) require in-depth analysis and discussion. It would be beneficial to include p-values and confidence intervals to convey the strength of the observed differences and their clinical significance. Additionally, exploring potential correlations between choroidal thickness and clinical parameters within each group could provide further insights. To enhance the credibility and completeness of the study, it is essential to discuss potential limitations. For example, addressing any selection biases, the representativeness of the study population, and the generalizability of the findings would strengthen the overall interpretation. Additionally, consider mentioning any challenges faced during data collection, potential confounding variables, or limitations associated with the chosen measurement techniques. Providing these details will help readers critically assess the study's validity and applicability to broader clinical contexts.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12769",
"date": "14 Nov 2024",
"name": "Yasser K. Al-Rubiay",
"role": "Author Response",
"response": "Dear Colleague Thank you for reviewing my article, I'm very grateful, I'll try to make all the changes you have kindly suggested, please find individual answers to the points you have raised. I've also uploaded a new corrected version of the article. 1-The innovative aspect of this study should be explicitly highlighted. For instance, detailing any novel methodological approaches, specific advancements in OCT technology, or unique aspects of the study population that set it apart from previous work would enhance the understanding of its contribution to the field. -The main innovative aspect of the study is the new swept source OCT machine, the first swept-source OCT was used, which at the time of the study was state of the art. 2-The statement, \"Group C comprised 33 eyes that were included in the study as healthy controls,\" does not specify which eyes from the control group were included. Clarity is needed on whether both eyes of each control participant were considered or if only one eye was randomly selected for inclusion in the study. -Right eye for all controls. 3-The study's comparison between \"group A\" (eyes with active CSCR) and \"group B\" (unaffected opposite eyes) is crucial for understanding the bilateral effects of CSCR. The statistical comparisons between these two groups (A vs. C and B vs. C) require in-depth analysis and discussion. It would be beneficial to include p-values and confidence intervals to convey the strength of the observed differences and their clinical significance. Additionally, exploring potential correlations between choroidal thickness and clinical parameters within each group could provide further insights.? -P values are already there for A vs C and B vs C, but no confidence intervals, We also specifically controlled for clinical parameters that might affect choroidal thickness between patients and controls, including refractive errors, and there was no significant difference in patient demographics. 4-To enhance the credibility and completeness of the study, it is essential to discuss potential limitations. For example, addressing any selection biases, the representativeness of the study population, and the generalizability of the findings would strengthen the overall interpretation. Additionally, consider mentioning any challenges faced during data collection, potential confounding variables, or limitations associated with the chosen measurement techniques. Providing these details will help readers critically assess the study's validity and applicability to broader clinical contexts. -Regarding limitations, the sample size was an issue, but this was because of the incidence of the disease, the study location is a tertiary hospital in the capital city of the country and people are referred from different cities to the hospital, people from low socioeconomic background might be under-represented in this study because of the cost of transport for example, also access to FFA was not always available, additionally these controls are not a representative sample of the population, because we controlled for refractive errors and hypertension for example"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1554
|
https://f1000research.com/articles/13-1364/v1
|
14 Nov 24
|
{
"type": "Review",
"title": "Digital and Financial Literacy for Uplifting Women and Achieving Sustainable Development Goals",
"authors": [
"Deepak Mishra",
"Vinay Kandpal",
"Naveen Agarwal",
"Rakesh Kumar",
"Rajesh singh",
"Neeraj Priyadarshi",
"Bhekisipho Twala",
"Deepak Mishra",
"Naveen Agarwal",
"Rakesh Kumar",
"Rajesh singh",
"Neeraj Priyadarshi",
"Bhekisipho Twala"
],
"abstract": "Digital and financial literacy are changing the landscape of the globe in terms of its approach to development. These two literacies also help to achieve women’s empowerment and, consequently, the sustainable development goals (SDGs) more quickly. This systematic literature review looks at the two literacies and their effects, focusing on women’s participation and showing how digital literacy not only increases women’s access to knowledge and connectivity but is also a door to women’s entrepreneurship and financial independence. Likewise, financial literacy, when coupled with digital skills, can be a breakthrough to the traditional socioeconomic barrier – poverty – by assisting women in making informed economic decisions, increasing their financial independence and resilience in the face of a global crisis. Empirical realities that still hinder women’s education, such as cultural norms, infrastructural deficiencies and educational gaps, still exist. However, the paper points out that to have a more equal world based on the SDGs, the double literacy strategy for women’s empowerment should not be negotiable.",
"keywords": [
"Digital literacy",
"financial literacy",
"Women's empowerment",
"Sustainable development goals",
"Economic independence",
"Entrepreneurial amenities",
"Socioeconomic barriers"
],
"content": "1. Introduction\n\nThe modern digital world is quite different from the world we would have known only a few decades ago. Significant developments in technology and digital transformation have already transformed several industries and aspects of our lives in significant ways. Globally, the factors that reflect a country’s development and progress includes financial inclusion, literacy, and female workforce participation (Duflo, 2012). Nonetheless, this also involves women in household financial decisions, which results in better financial health (Haque & Zulfiqar, 2016).\n\nThere is already evidence that greater female financial independence leads to more spending on families, resulting in broad societal benefits such as greater health and education (Doepke et al., 2011). There is also evidence that greater female employment and earnings correlate with better economic growth and lower gender wage gaps (Goldin, 2014). For women in settings with societal or regulatory barriers, digital platforms currently offer greater opportunities than ever before for earning and learning (World Bank, 2016) and building cross-regional networks and collaborations to break down the insider silos of the past (Huyer, 2016). Identifying the cross-cutting power of women’s empowerment (SDG 5) on other SDGs (e.g., reduced poverty, SDG 1; improved health, SDG 3; and others) is critical (UNDP, 2016). In addition, the positive connections between financial and digital literacy and SDGs such as Quality Education (SDG 4) and Decent Work (SDG 8) are emerging (UNESCO, 2017), and more detailed insights into the nexus of literacy, women’s empowerment, and SDGs can facilitate more focused, targeted, and effective policy interventions (World Bank, 2018).\n\nFinancial literacy positively relates to intelligence, where meta-analyses report moderate to large effect sizes. Studies show that financial literacy has become more important over time due to increased responsibility for personal retirement planning, growing access to financial goods, the rise of the gig economy, and innovations in fintech services. Financial literacy has also become more relevant amid the recession caused by the COVID-19 pandemic, as individuals face higher levels of financial distress. A recent analysis using survey data spanning 2015-2020 from the US Federal Reserve Board reveals that Americans’ sentiment about their financial lives had significantly improved prior to COVID-19. However, financial stress showed an overall increase following the pandemic, which also caused unemployment rates to soar (Morgan et al., 2019; Walker et al., 2023).\n\nIn recent years, some scholars have seen growing interest in examining the impact of financial literacy on people’s economic decisions. Simultaneously, there has been an increasing provision for understanding and measuring the concept of financial literacy. Today, financial literacy learning has become an essential self-management skill for people living in a family and business activities (Vieira et al., 2020). Rapid changes in the global economy require financial literacy to adapt to new financial models (Demirguc-Kunt et al., 2018). It is seen as a predictor of individual differences in investor attitudes. Cryptocurrencies are negatively associated with higher levels of intelligence after controlling for financial literacy and narcissism, potentially due to the mechanism of cynicism.\n\nThe rationale for researching digital and financial literacy in relation to women’s empowerment and the SDGs is based on the premise that the empowerment of women is a condition not only of social equity but also of the innovation and efficacy of approaches aimed at attaining ever more ambitious and transformative development goals. In the 21st century, digital and financial literacy will be the key to ensuring that the individuals and communities of today and tomorrow have the capacity to adapt, innovate and prosper. This review will set out how digital and financial literacy affect women’s empowerment and the extent to which women’s empowerment, in turn, affects the framing and delivery of the SDGs. We will map out the literacies’ direct and indirect impacts, highlight successful global initiatives, highlight current challenges, and develop recommendations that can inform policy and strategy for women’s empowerment through improved literacy.\n\n\n2. Literature review\n\nFinancial well-being is the state of satisfying all of one’s current and ongoing financial obligations, feeling secure about one’s financial future, and making life-enhancing decisions (Hudson et al., 2022). More specifically, an individual’s financial well-being corresponds to the extent to which the individual feels that he or she (1) has control over day-to-day and month-to-month finances, (2) can absorb a financial shock, (3) is on track to meet his or her financial goals, and (4) has the financial independence to make the decisions that permit one to appreciate life (Weida et al., 2020). Although specific goals and visions of a good life vary from person to person, these four elements reflect two common and consistent themes: security and freedom of choice in the present and for the future. Retirees display high financial literacy, and together with debt anxiety, this is significantly correlated with resource allocation preferences. Financial literacy reduces debt anxiety in men, increases women’s risk tolerance, and is associated with a higher priority for KiwiSaver. Greater debt anxiety is associated with debt repayment, and debt avoidance in old age is critical to long-term well-being (Noviarini et al., 2023).\n\nFinancial literacy refers to the comprehension and awareness of financial principles and potential hazards, along with the abilities, drive, and self-assurance to utilize this knowledge and understanding to make sound choices within diverse financial situations. Its objective is to enhance the financial well-being of individuals and society and promote active involvement in economic activities (Méndez Prado et al., 2022). As in the definition of any PISA domain, the first part of the definition concerns reasoning and behavioral traits that ‘are characteristic of the domain,’ and the second part focuses on why literacy in that specific domain was defined. We find a positive relationship between people with higher levels of financial literacy and persons inclined to Socially Responsible (SR) financial investments, and people inclined to SR financial investments are more likely to favor SR financial intermediaries. Compelling evidence of our result emerges by using different numbers of neighbors. SR investors or those with a higher level of financial literacy are more likely to favor SR financial intermediaries. This implies that in order to attract financially literate customers or SRI retail investors, financial companies must do more than offer traditional and SRI products. In order to become sustainable intermediaries, they need to adopt environmental, social and governance (ESG) strategies (Cucinelli & Soana, 2023).\n\nThere is a plethora of studies that have examined the link between financial inclusion, financial literacy, and sustainable development and how they are mutually enhanced. However, there is a dearth of literature that explicitly explores this link from the lens of rural agrarian communities, which require development opportunities in finance rather than financial literacy (Akande et al., 2023), and where a more important emphasis should be placed on the role of financial literacy in influencing and improving financial behavior. This link between financial literacy and financial behavior has important implications. The role of limited attention in explaining the positive association between financial literacy and formal bank account ownership, financial market participation, commercial insurance, pension plan ownership and credit card ownership supports the view that individuals with higher levels of financial literacy are more likely to benefit from such counsel due to the ability of greater financial literacy to improve access to specific financial information (Xu et al., 2022). Therefore, we reason that ceteris paribus, individuals with higher financial literacy are more likely to engage in the pursuit of such counsel actively. Furthermore, the extant literature reveals that there is a positive correlation between financial literacy and financial behavior, and specifically, those requiring financial counseling with greater levels of financial literacy are more likely to utilize financial counsel (Liu & Lu, 2023).\n\nThe ability to use digital technologies in an effective and responsible manner is referred to as digital literacy. It is inextricably tied to the specific skills, knowledge, and attitudes that lead to utilizing digital devices, applications, and online platforms for communicating, finding information, critiquing, problem-solving, innovating, and creating. The use of Industry 4.0 technologies, such as financial technology (Fintech) and the strategic utilization of organizational resources are major drivers of long-term sustainability and operational efficiency in firms (Siddik et al., 2023).\n\nFinancial literacy refers to its knowledge, skills, and understanding of financial ideas and principles to make informed choices about financial resources. In the concept of financial literacy, we can find several issues connected with personal finance, including budgeting, savings, investment, borrowing, and debt management. Financial literacy links with the knowledge and understanding of available financial products and services, such as bank accounts, loans, credit cards, insurance, and investments. It also refers to the knowledge of financial information, including statements, budgets, and other documents needed to manage finances, and the ability to analyze what the financial information is delivering for the individual. It also concerns smart decision-making about finances to enable the accomplishment of some short- and long-term financial goals (Lusardi & Mitchell, 2014). Financial capabilities work as a mediator between financial literacy, digital financial literacy, and financial decision-making. DFL is a new concept, and it has received less attention in the field of academic papers. So far, fewer empirical papers have explored the direct effect of DFL on financial decision-making. Skills in the specific domain had a direct impact on decisions made about investing and, consequently, on perceptions of financial well-being. Digital financial literacy, being an indicator of financial decision-making, also emerged as a direct predictor and mediator. The impact of financial aptitude and autonomy as mediators of financial decision-making and well-being is clearer. On the other hand, the influence of impulsivity is almost insignificant in relation to financial decision-making (Kumar et al., 2023).\n\nThe idea of women’s empowerment is about enabling and increasing women’s social, economic, political, and personal resources and capabilities; the concept includes creating an environment in which women are free to make choices and decisions about their lives and work with equality. The advancement of women’s empowerment yields advantages not only for women themselves but also for the broader societal framework. Women’s empowerment enables them to contribute more effectively to various aspects, such as economic growth, poverty reduction, sustainable development, and social progress. This phenomenon fosters a societal environment characterized by inclusivity and equity when the rights and capabilities of every individual are acknowledged and esteemed. Women’s empowerment refers to the systematic progression through which women attain authority and autonomy, enabling them to exercise deliberate decision-making. It is suggested that there is a need for more targeted policies that can effectively address the existing gender gap to promote comprehensive financial inclusion (Ghosh, 2022).\n\nThe emergence and contribution of women entrepreneurs to the national economy have played a crucial role in the development of a burgeoning nation. Women have commenced making contributions to economic development through their distinct professional endeavors. Women have transitioned from their traditional roles as homemakers to become influential business leaders with the skills and determination to manage a firm and overcome obstacles for their advantage effectively. The increasing IT environment has created extra opportunities for women entrepreneurs to enhance the growth and success of their companies. One crucial aspect that is widely acknowledged as significant in decision-making and organizational activities is the ability to conceptualize and benchmark work. The promotion of positive behavior in women’s entrepreneurship within a specific cultural and societal context serves to enhance empowerment (Andriamahery & Qamruzzaman, 2022).\n\nThe terms “resilience” and “resiliency” have gained significant prominence in discourse since the onset of the mortgage meltdown and subsequent financial crisis. Financial resilience refers to an individual’s capacity to endure and recover from life circumstances that harm their income or assets. The longer-term perspective pertains to one’s connection with finances. Financial inclusion initiatives aim to improve the accessibility of financial services for vulnerable populations, fostering greater inclusivity and financial resilience within societies. The rise of the fintech industry and digital means of payment, coupled with the fact that more than two-thirds of the world’s population now own a mobile phone, all indicate how digital financial literacy is now taking hold in societies worldwide. In response to this shift, it is time to reimagine financial literacy by blending it with digital literacy – something that has important implications for countries aspiring to adopt either a dual-track or a combination approach to improving the long-run resilience of households (Kass-Hanna et al., 2022).\n\nIndia has the highest percentage of inactive bank accounts in the world, at 35 percent (Dhanamalar et al., 2020). According to the Findex survey, 2021, more than 32 percent of women-owned bank accounts in the country are inactive. The country shows the highest gender gap in inactivity, with a difference of 12 percentage points. Surprisingly, fewer than one in five banked women save formally with the bank (World Bank, 2021).\n\n\n3. Methods\n\nWe present systematic literature review (SLR) methods to provide an overall analysis and constructive evaluation that investigate, identify, and offer rectification for possible issues for future research. According to Massaro et al. (2016), SLR is a systematic approach to analyzing scholarly literature to identify insights, provide critical reflections, offer new research directions, and ask research questions.\n\nThe SLR method collects all the articles on a particular research question and examines it in a systematic manner (Mukherjee et al., 2017). It helps make the review impartial and transparent. It is exhaustive and not as casual as a traditional review (Bryman, 2012; Choong, 2014). This study first searched, found and reviewed the financial inclusion and sustainable development literature published from 2013 to 2023 using key terms such as ‘digital and financial literacy,’ ‘financial well-being’, ‘financial resilience’, ‘financial decision making’, ‘investment behavior’, ‘women’s empowerment’, and combines them into the subject level. The papers were then filtered after setting the scope of the review by using the scientific qualification type such as ‘empirical, review papers’, etc. Articles were investigated first and sieved from high-quality and high-impact journals, which are listed in electronic databases such as Scopus, Web of Science (WoS) /Social Science Citation Index (SSCI)/Journal Citation Report, which holds the list of academic journals with an IF. This search helps to find possible sources of review (Paul et al., 2017). Literature search must be extensive and use as much database as possible. It is advisable to use many databases with a risk of getting duplicate articles, but it minimizes the chance of missing a significant publication (Vieira & Gomes, 2009). The initial stage of the literature search identified 1045 research articles. Further work was done to refine 85 papers, which were studied and scrutinized for the review type and classification of research, and to categorize them by type of study primarily focusing on India and emerging economies. Conference proceedings and book chapters were excluded from the research work. Extractions from Scopus and WOS for this study were made on December 30, 2023. The articles selected were analyzed and understood thoroughly, considering the topic’s relevance. The research also included secondary data sources such as reports published by institutions such as the World Bank, Asian Development Bank, UNESCO, and ILO.\n\n\n4. Discussion\n\nThe 2030 Agenda for Sustainable Development advocates for a novel and transformative vision. It outlines 17 linked and indivisible Sustainable Development Goals (SDGs), prioritizing gender equality. Gender equality and women’s empowerment are explicitly prioritized through stand-alone Goal 5 and are integrated throughout the Sustainable Development Goals (SDGs). The UN 2030 Agenda acknowledges multidimensional inequality both inside and within nations, committing to the principle of “leaving no one behind.”\n\nThe Asian Development Bank (ADB) and the UN Women’s Regional Office for Asia and the Pacific collaboratively conducted the inaugural extensive assessment of gender equality and women’s empowerment in the Asia and Pacific region within the context of the Sustainable Development Goals framework (The Asian Development Bank & UN Women, 2018). Financial inclusion is regarded as a vital metric of progress and is recognized as a facilitator for at least eight of the 17 Sustainable Development Goals (SDGs). Access to bank accounts, loans, insurance, and other financial services directly enhances health, education, and employment results.\n\nIn turn, such progress helps achieve the collective goals of eradicating poverty, promoting inclusive growth, and reducing inequality. Every transformation initiative delineates crucial investments and regulatory obstacles, necessitating coordinated efforts from certain government entities in collaboration with the private sector and civil society. Hence, it is possible to implement transformations inside governmental frameworks while acknowledging the significant interconnections among the 17 Sustainable Development Goals (SDGs) (Sachs et al., 2019).\n\nMapping emergent opportunities for digital and financial literacies could be likened to the interlacing of two strands of thread. Each strand both complements and strengthens the other and, depending on how much it is intertwined, the combination yields a stronger, more dynamic whole. The sum of these two literacies together is greater than the two components on their own. The integration of digital and financial literacies can improve favorable outcomes by the following:\n\nIncreased access and outreach: Digital democratization of financial knowledge has the potential to increase access and outreach by providing members of the public access to a wider range of financial education materials, tools, and services via the Internet. One of the major benefits of the digital age has been the democratization of financial knowledge, which has allowed many people, irrespective of where they live or what their economic status is, to have access to this information via online courses, apps, or websites.\n\nBetter financial decision-making: The digitally savvy person can use a range of online tools, such as budget trackers, investment apps, and online banking, to help make sound financial decisions. Organizations can quickly assess, evaluate, and act on their financial data, thus making better use of their financial information and, as a result, having better financial governance.\n\nEmpowerment due to Information: Information is widely available on the Internet, and people can use it to become empowered. Women now have access to information on their rights, benefits, and opportunities via the Internet, which helps them earn more money and be more independent.\n\nBetter economic participation: Digital technologies enable women to gain better economic participation by taking advantage of the gig economy, e-commerce or other online ventures with digital financial literacy, thereby improving their economic status.\n\nSecurity and transparency: As long as someone has a good understanding of the process involved, digital financial transactions can be more transparent and secure than more traditional methods. In places where women’s access to funds may be restricted, women must be able to exercise covert control over their resources.\n\nBroader networks and horizons: Digital literacy means access to networks, communities and markets beyond the geographic area, providing opportunities and potential for growth. With connectivity, alongside financial literacy, greater entrepreneurial opportunities and the possibility of forming mutually productive partnerships could come.\n\nPersonalized digital financial solutions: Through advanced digital financial platforms enabled by AI and ML technologies, users can receive personalized digital financial recommendations to enhance their financial well-being. Users with sufficient digital literacy skills can explore and access these personalized recommendations to their advantage.\n\nPromotion of Sustainable Finance: Although the goals of sustainability are gaining ground at an international level, it is still incumbent upon digital platforms to promote sustainable finance so that people can make the right investment decisions. Digital literacy helps in procuring and utilizing the information and analysis available regarding ethical investments and sustainability-focused financial goals. People with digital literacy can match their financial strategy to the goals of global sustainability.\n\nWomen can use green microfinance to increase their financial literacy and become more empowered, thanks to their local knowledge and experience. In this case, the indigenous knowledge came from the women’s adherence to the ancestral worship tradition for their Marapu deities. The study aimed to understand if strengthening the pro-literacy (SDG 4) policy could help the government at the local level achieve its goals related to gender equality (SDG 5) and climate change (SDG 13) (Pathak et al., 2022).\n\nDigital literacy provides access to a vast digital space with tremendous opportunities, while financial literacy provides the necessary understanding to make the best use of the space. Together, they provide an enabling environment for individuals, especially those who are disadvantaged, such as women, to get access to resources, make informed choices, and build a resilient economic life. The integration process is not only to help people develop their agency but also to promote the growth of the overall economy and stability and further the goal of building a community with a shared future for mankind, a community of shared destiny that is inclusive, fair, and rich. There is a persistent inequality in the access, use, and benefits of digital financial services between genders and socioeconomic statuses and between urban and rural areas in developing countries. By the time we finished the study, we made several recommendations. Most of them were related to better digital infrastructure, simplifying the complex nature of conventional banking, and promoting the importance of financial education, all to support the development of digital financial inclusion in the world (Tay et al., 2022).\n\nPatriarchy as a structural barrier, psychological barriers, low income/wage, low financial literacy, lack of financial access, and ethnicity are a few of the barriers that were identified as hindering women’s empowerment. Our extensive literature survey further identified six well-evidenced interventions that were brought about by the government and corporate sector, namely: government/corporate programmes and policies, microfinance, formal savings accounts and services, cash and asset transfer programmes, self-help groups, and digital inclusion. To conclude, although ample research has been conducted in this area, still the literature has excessive gaps, which need to be explored further.\n\nThe present study investigates two crucial theories. The theory of planned behavior (TPB) and the technology acceptance model (TAM) are two prominent theoretical frameworks that have significantly contributed to the comprehension of human behavior, particularly in relation to the acceptance and utilization of technology.\n\nThe theory of planned behavior suggests that individuals adopt a very rational decision-making process where they weigh up the pros and cons of their chosen course of action. The theory of reasoned action and the theory of planned behavior both apply to situations where there are arguments for choosing to act or arguments for not choosing to act. According to the theory of planned behavior, the intention is the main determinant of behavior – and what we intend to do is to either do or not do a particular thing. Three aspects of preferences influence the formation of intentions: (i) attitude, that is, one’s evaluation of whether to do or not do a particular thing; (ii) subjective norm or one’s perception of whether other people think that one ought to do, or not do, a particular thing; and (iii) perceived behavioral control or one’s perception of how able or unable one is to do the thing in question.\n\nThe Theory of Planned Behaviour, one of the most popular theories in social psychology, has been extended by adding perceived behavioral control to offer a complete account of people’s behavioral intentions. General, specific, and situational goals, acting together with measures of behavioral control beliefs, allow for precise predictions of diverse behavioral intentions. Goals plus behavioral control beliefs can account for the range of actual behavior. Together with attitudes and subjective norms, perceived behavioral controls are associated with distinct sets of salient behavioral, normative, and control beliefs, which are specific to the target behavior under consideration. However, the exact nature of these relations remains to be specified. The theory identifies and draws upon three distinct groups of factors.\n\n1) Perspectives or dispositions\n\n2) Subjective norms and prescriptive influence\n\nPerceptions of behavioral control refer to a person’s belief that he or she can perform a behavior or task adequately, which recognizes the many factors (internal and external) that can affect the person’s capacity for action.\n\n1) The Impact of Attitudes on Financial Decision Making:\n\nAn attitude is a predisposition, affective orientation, or learned tendency to respond favorably or unfavorably towards an idea, individual, or instance. It constitutes the enduring mental framework an individual employs in their interpretation and evaluation of a concept, entity, person, or situation (Vargas-Sánchez et al., 2016). There is also evidence suggesting that financial attitude and financial literacy are positively correlated with the choice of financial instrument, and financial behavior serves as a mediating factor. Rai et al., (2019) investigated whether financial attitude can enhance decision-making and whether financial behavior can mediate this process. The results provide a solid basis for their belief that financial attitude and financial literacy have a positive influence on financial behavior.\n\n2) Effects of perceived subjective norms and prescriptive influence on financial decision-making :\n\nWayne, (2022) addressed whether or not the respondent felt that society would approve or disapprove of certain actions. This pertains to an individual’s contemplation of the perceptions of their peers and individuals of significance toward their potential involvement in a particular behavior. Vyvyan et al., (2014) examined the impact of several factors on financial decision-making and effectiveness. The study’s findings indicated that learning behaviors exhibited within the familial context were perceived as influential in shaping individuals’ future financial behavior.\n\n3) The impact of perceived behavioral control on financial decision-making :\n\nPerceived behavioral control pertains to an individual’s subjective assessment of ease or difficulty associated with engaging in certain behaviors. The level of self-assurance that somebody possesses in their capability to perform a task substantially influences their subsequent actions. Self-efficacy is crucial in elucidating the connections among beliefs, attitudes, intentions, and behavior. Financial self-efficacy has been identified as a significant determinant of consumer financial decision-making power, as stated by Xiao et al. (2015). Similarly, it was also discovered that the perception of financial decision-making capabilities tends to rise with advancing age.\n\nIn the face of these technological advancements and the fact that the aim of digital literacy is more or less aligned with the 2030 Agenda under the goal of women’s empowerment (and other sustainable development goals, or SDGs), the digital-financial space seems an appropriate context in which to apply the TPB, the TAM and other important models, and to test and refine them for broader applicability. This review of behaviors and technology adoption in this inter-integrated context should help us discern both the flexibility and the limitations of these models. Thinking about ‘perceived behavioral control’ in the context of digital financial literacy might also require a redefinition: perhaps when linked to digital finance, it would be appropriate to consider the existence of underlying social norms or even infrastructure constraints that might transform this construct considerably. In the TAM, we have ‘perceived usefulness’ related to the goal of digital finance, which refers less to the fact that the task is being completed than to more general life goals, such as empowerment and sustainability.\n\nThe integration of digital instruments into financial decision-making allows for the examination of the interplay between the TPB and TAM constructs. For instance, how does behavioral intention, as proposed by the theory of planned behavior (TPB), impact the usefulness of the technology acceptance model (TAM)? Findings could start to lay the framework for a unified model. Moreover, an analysis of cultural differences might help develop culturally adapted theoretical models, which are vital for global applicability. The environment may be different, hence generating the discovery of important new constructs or dimensions that are not incorporated in the existing theories. Community might be one of the influential factors that emerges in the acceptance of digital financial literacy. This review paper explores the interplay among digital and financial literacies, women’s emancipation, and sustainable development goals (SDGs), aiming to develop more holistic and situation-based frameworks consistent with current global challenges and expectations.\n\n\n5. Conclusion\n\nThis article reviews the role of digital and financial literacy and women’s empowerment in their contribution to the Sustainable Development Goals (SDGs). Our findings show that there is a strong two-way causality between women’s digital and financial literacy and their empowerment. It also confirms that improving women’s literacy holistically not only empowers women but also facilitates the achievement of many SDGs. Digital and financial literacy are not only tools but also vehicles. They are bridges that take women across established social boundaries and connections towards other groups around the globe and more fully into the economy. We have seen that empowering women is pivotal to their countries’ sustainable growth, poverty alleviation and equal societies.\n\nLarge literacy gaps – most notably in Africa and Asia – involve challenges as well as opportunities. Smart investments in literacy in these areas promise to add a multiplicative effect and deliver payoffs in health, education and welfare. Many case studies and projects mentioned show that the route to women’s empowerment through digital and financial literacy, however difficult, is navigable and worthwhile. From grassroots initiatives to global campaigns, governments, nongovernmental organizations, and the corporate sector can work together to create an atmosphere favorable to learning and empowerment. There is a significant gender disparity in financial resilience, whereby men exhibit greater levels of financial resilience behaviors than women. A positive correlation exists between women who are employed and women who have attained higher levels of education and their ability to exhibit enhanced financial resilience (Zeka & Alhassan, 2023).\n\n\n6. Scope for future research\n\nDigital and financial literacy and issues of gender – as they are associated with improved women’s empowerment and the fulfillment of sustainable development goals (SDGs) – is in itself a wide and fast-expanding field. The shifts and transformations we have observed over the past decade already highlight the vastness of potential vistas, the richest to be further explored by both academics and practitioners. A holistic, global framework, however, can only scratch the surface of what it takes to advance the field and create the best conditions for all women to become fully included in the gains of the digital and financial worlds. As much as the socioeconomic indicators aggregate on the surface, complexities inherent in regional scenarios and diversity require more granular analysis. It is justifiably helpful to deepen the insights from the variations of digital and gender societies in more specific contexts, such as the Southeast Asian landscape, where fast urbanization and cultural factors create an interesting dynamic, or in the Middle East, where sociopolitical factors strongly influence women’s trajectory in both digital and financial spheres. Even within regions, differences can be significant. In Africa, for instance, the gap between the pastoral settlements in the Sahel and the urban settings in South Africa can be radical, each presenting its own set of challenges and opportunities.\n\nWe also need to understand the growing digital divide: while urban areas – as well as the industrialized parts of the world – are moving towards a hyper-connected future, many people, especially women in rural areas, are left behind, without even basic digital infrastructure. Solutions to close the gap, from low-tech digital interventions to community-level initiatives, need to be researched. The role of the private sector, particularly large technology, and financial companies is also worth investigating. Linking other identity components, such as ethnicity, socioeconomic status or age, to gender offers another avenue to a richer, more nuanced understanding.\n\n\n7. Policy implications\n\nThe findings of the digital and financial literacy paradigm of women’s empowerment and the achievement of the SDGs have implications for all strata of people, which creates disruptive changes at the individual and societal levels. The implications at the policy frontier is far-reaching. Policymakers have a data-driven paradigm to guide them to develop new evidence-based approaches to advancing gender-equitable empowerment in new spaces. The findings highlight the need to teach digital and financial literacy in existing academic curriculums and for education institutions to evolve into knowledge spaces that foster not just the delivery of the requisite skills to navigate contemporary society but also their development. The implications of the study of digital and financial literacies, women’s empowerment, and their SDGs transcend academic endeavors and are relevant in the policymaking, NGO efforts, technology company mission, and global development strategy space. These implications are particularly pertinent to the synergies between digital and financial literacies, women’s empowerment and the SDGs.",
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}
|
[
{
"id": "341083",
"date": "02 Dec 2024",
"name": "Nurul Hidayana Mohd Noor",
"expertise": [
"Reviewer Expertise Women and gender studies",
"entrepreneurship",
"youth studies",
"and organizational management."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is an exciting topic, yet several suggestions exist for improving the current paper. The recommendations are as follows:\nMost of the citations in the introduction part are obsolete. Please replace them with the recent ones. More sentences should be added to the introduction to highlight the issues faced by women (lack of financial literacy and digital financial literacy). Please provide evidence and statistics. In the LR section, some sections are irrelevant (e.g., financial resilience and women empowerment). Perhaps you can combine these two sections into one section, such as The Challenges faced by Women in Achieving Financial Well-Being. Thus, under this one section, the authors can discuss the financial well-being concept, financial constraints, and strategies to empower women to achieve financial well-being. Then, follow with the financial literacy section and digital financial literacy section. Please make sure all citations are at the latest (2019-2024). And please diversify your citations. The SLR technique is not straightforward in the methodology section because the authors do not determine the method used. For example, ROSES or PRISMA. It would be better if the researchers could provide diagrams for conducting SLR. For example, the PRISMA flow diagram (please check on it). The inclusion and exclusion criteria for articles need to be clearly stated. Discussion- rename it into findings and discussion The most critical flaw in this article is your findings/discussion part, where the researchers are encouraged to organize it into research objectives. Because the readers are not clear from the introduction section. For example, in the introduction section, the authors need to list out the sub-objectives of their paper. For example:\n\nTo identify the impact of financial literacy To assess the importance of digital financial literacy For instance, the current trends of research in financial and financial digital literacy (i.e., the theory underpinning and methodological aspects) Xxxx\nThus, organizing your findings and discussion will be more apparent because you can discuss your SLR findings based on the objective. The current content is confusing and not clear. After you have presented your findings. You can consult the theoretical, policy, or practical contributions and close the manuscript with the conclusion section.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nIs the review written in accessible language? Partly\n\nAre the conclusions drawn appropriate in the context of the current research literature? Partly",
"responses": [
{
"c_id": "12960",
"date": "17 Dec 2024",
"name": "Vinay Kandpal",
"role": "Author Response",
"response": "The recommendations are as follows: Most of the citations in the introduction part are obsolete. Please replace them with the recent ones.- Literature updated in Introduction and LR More sentences should be added to the introduction to highlight the issues faced by women (lack of financial literacy and digital financial literacy). Please provide evidence and statistics. Literature and supporting statistics updated in Introduction and LR In the LR section, some sections are irrelevant (e.g., financial resilience and women empowerment). Perhaps you can combine these two sections into one section, such as The Challenges faced by Women in Achieving Financial Well-Being. Thus, under this one section, the authors can discuss the financial well-being concept, financial constraints, and strategies to empower women to achieve financial well-being. Then, follow with the financial literacy section and digital financial literacy section. Please make sure all citations are at the latest (2019-2024). And please diversify your citations. Diversified citations included. The suggested two sections clubbed into one section The SLR technique is not straightforward in the methodology section because the authors do not determine the method used. For example, ROSES or PRISMA. PRISMA included in Research Methods It would be better if the researchers could provide diagrams for conducting SLR. For example, the PRISMA flow diagram (please check on it). The inclusion and exclusion criteria for articles need to be clearly stated. PRISMA included in Research Methods stating the inclusion and exclusion. Discussion- rename it into findings and discussion: Suggested Changes made in the revised paper. The most critical flaw in this article is your findings/discussion part, where the researchers are encouraged to organize it into research objectives. Because the readers are not clear from the introduction section. For example, in the introduction section, the authors need to list out the sub-objectives of their paper. For example: To identify the impact of financial literacy To assess the importance of digital financial literacy For instance, the current trends of research in financial and financial digital literacy (i.e., the theory underpinning and methodological aspects Thus, organizing your findings and discussion will be more apparent because you can discuss your SLR findings based on the objective. The current content is confusing and not clear. After you have presented your findings. You can consult the theoretical, policy, or practical contributions and close the manuscript with the conclusion section. Suggested Changes incorporated in revised Version of paper."
}
]
},
{
"id": "348865",
"date": "17 Dec 2024",
"name": "Maria Alzira Pimenta Dinis",
"expertise": [
"Reviewer Expertise Sustainability"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is unclear the region addressed in the title or if global scope The abstract would need to clarify the specific findings as further practical implications The Introduction needs to cite more recent references as connecting paragraphs. This is applied to the entire piece of text The literature review reveals some expressive similarity, which is also present I the methods section and the discussion section (there seems to be no results section…) All the content mentioned here needs references, as it resulted from the literature review: “4.1 Synergy between digital, financial literacy, women’s empowerment and SDGs” It is not clear to me why this is the point two of the “discussion”: “4.2 Underpinning theories” This part needs references again and further connection “4.4. Theoretical contributions” The conclusions section could address context and methods, findings and implications, limitations and future prospects, all here. The entire articles needs to address full cohesion and streamlining Authors needs to highlight novelty and relevance, compared to existing studies. All older references should be revised As presented, the text is just too descriptive, missing the necessary tables and graphics or schemes\n\nIs the topic of the review discussed comprehensively in the context of the current literature? No\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nIs the review written in accessible language? Partly\n\nAre the conclusions drawn appropriate in the context of the current research literature? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1364
|
https://f1000research.com/articles/13-1363/v1
|
14 Nov 24
|
{
"type": "Research Article",
"title": "Teaching Self-efficacy and Teaching Methods in the Aquatic Environment",
"authors": [
"Rita Fonseca-Pinto",
"Juan Antonio Moreno-Murcia",
"Juan Antonio Moreno-Murcia"
],
"abstract": "Background Studies have shown that perceived self-efficacy can influence teachers’ emotional state, thoughts and behaviours, and students’ learning. It’s also an important referential of professional satisfaction. In turn, teaching methodologies influence motor learning, as well as psychological, cognitive and social learning, with different impacts on human development and learning retention, levels of intrinsic motivation and continuity of practice in order to support a healthy lifestyle. Research on aquatic educators and teaching methodologies is scarce and at the same time necessary according to the view that aquatic literacy is an integral part of physical literacy and the only possibility of being more able to interact with this environment.\n\nMethods In this study we used an online questionnaire, aimed at aquatic professionals, which was answered voluntarily and anonymously to measure the prevalence of the use of different teaching methodologies, the comprehensive aquatic method and the perception of teacher self-efficacy. It has been deposited and can be consulted at https://doi.org/10.6084/m9.figshare.27316242.v1.\n\nResults All methods can generate a feeling of self-efficacy in teachers despite having different results, with the methodologies that involve students more actively (cognitivist and constructivist) being those that generate a greater feeling of self-efficacy in teachers. MAC is a method that is more closely related to methodologies focused on active student participation and, consequently, it is a method that generates a high perception of self-efficacy in teachers.\n\nConclusions Levels of self-efficacy influence professional satisfaction, teacher physical, mental and emotional health, as well as student learning. Is recommended that aquatic professionals give prevalence to the cognitivist and constructivist teaching methodologies being MAC a privileged methodological approach for promoting active lifestyle habits throughout life.",
"keywords": [
"methods",
"aquatic literacy",
"teaching",
"self-efficacy"
],
"content": "Introduction\n\nConsidering aquatic literacy as an integral part of physical literacy (Albarracín & Moreno-Murcia, 2018), allows to increase the vision on the contents and impact of school physical education. The development of aquatic literacy, as part of a larger concept called water competence, in the school-aged population can contribute to the reduction of physical inactivity and is certainly determinant for the prevention of drowning not only at school age but also in the adult future. In order to reach as many children and youth as possible, it is necessary to make the practice accessible to all, and only the school has this inclusive opportunity. But it is not enough the content that can be offered to the students, it is important to value how this content is shared considering the benefits for the teacher, for the student and the retention not only of the learning but more than anything else of the enjoyment of an active lifestyle, which finds in the aquatic activities one more way to stay active in the long term. In this sense, the study of teacher self-efficacy, considered as a key element for professional satisfaction, motivation (Ortan et al., 2021) and emotional self-regulation of the professional (Shahzad & Naureen, 2017), has been considered a priority in the field of the specificity of the professionals responsible for the aquatic education of school children. According to Bandura’s (1977, 1997) theory, self-efficacy refers to people’s beliefs about their abilities to successfully carry out the actions necessary to complete a specific task. In turn, and according to the view of, Ainley & Carstens (2018) define self-efficacy as “the beliefs that teachers have about their ability to implement certain teaching behaviours that influence students’ educational outcomes, such as achievement, interest and motivation”. These beliefs are influenced by experience and, more specifically in education, are reflected in teachers’ beliefs that they can perform behaviours that produce results or outcomes. These types of personal beliefs tend to be rigid (Ortan et al., 2021). So, from a theoretical perspective, teacher self-efficacy is a multi-faceted affective construct (Zakariya 2020).\n\nPeople with a high sense of self-efficacy tend to see themselves in a successful situation, which is a positive incentive in their performance (Schwarzer et al., 2000), are more confident and have greater pro-activity in task solving (Peng & Mao, 2015). In contrast, people with a low sense of self-efficacy are more prone to depression, anxiety (Bandura, 1997) and to have more problems with student discipline and behaviour (Ortan et al., 2021). Perceived teacher self-efficacy is an essential element that can influence teachers’ thoughts, behaviours and emotions (Bandura, 1997; Pendergast et al., 2011; Poulou et al., 2019), the receptiveness to experiment new methods in an attempt to meet the needs of the learners (Shahzad & Naureen, 2017), as well as student learning (Dellinger et al., 2008). However, most studies on teacher self-efficacy seem to focus predominantly on job satisfaction (Zakariya, 2020).\n\nFor several decades, attempts have been made to discover those teaching characteristics that best demonstrate high effectiveness in professional work (Korthagen, 2004; Koster et al., 2005), in order to configure an effective teaching style and thus make it possible to link teaching variables with self-efficacy (Avalos, 2011).\n\nTschannen-Mora & Woolfolk Hoy (2001) review all the sources in which the construct of teacher efficacy appears, concluding that teacher self-efficacy is not only related to student outcomes in terms of performance, motivation and self-efficacy, but is also to some extend linked to the behaviours that students display in the classroom as a result of the teacher’s methodological intervention. In this sense, relating information on the characteristics of teaching methodology (from more behaviourist to more constructivist perspectives) and teacher self-efficacy could help to determine which practices lead to greater benefits.\n\nA diverse range of teaching methodologies exists in educational contexts, often categorized as autonomy-supportive or controlling. The teacher’s approach significantly influences student learning outcomes, determining whether students succeed or struggle academically (Shahzad & Naureen, 2017; Woolfolk, 1998). Research indicates that teaching methodologies in sports not only affect technical, tactical, and physical skills but also psychological and social dimensions (Emmanouel et al., 1992). For instance, in aquatic skill instruction, the teacher’s influence extends beyond motor skills, impacting levels of intrinsic motivation.\n\nHealthy variability in teaching (Mosston & Ashworth, 2002) offers multiple, non-exclusive interaction options between teacher and student, emphasizing the importance of decision-making skills (Hein et al., 2015). One method is the reproductive methodology, characterized by a strictly teacher-directed approach where students merely replicate tasks. This behaviorist model relies on environmental reinforcement and leads to rote, repetitive learning based on stimulus-response dynamics (Hein et al., 2012).\n\nIn contrast, the productive, learner-centered methodology (Bechter et al., 2019) focuses on knowledge acquisition through creating mental structures and understanding learning processes (Dyson et al., 2004). Here, learners actively engage in problem-solving, evaluating alternatives based on their knowledge (Hein et al., 2012).\n\nThe constructivist methodology shifts the focus to students, allowing them to set learning objectives, select content, and choose assessment methods (Barker et al., 2014; Kirk & Macdonald, 1998). This approach fosters active participation, enabling students to solve problems with teacher support, thereby constructing their own understanding of the subject matter (Nuñez & Oliver, 2020; Goodyear & Dudley, 2015).\n\nA fourth approach, known as laissez-faire, involves minimal teacher intervention, where the teacher only organizes equipment and manages time and space without engaging with students during activities (Hein et al., 2012).\n\nThe evolution of pedagogy reflects a shift from instructional to constructivist methodologies, demonstrating that student-centered approaches yield significant benefits (Barker et al., 2014; Bechter et al., 2019; Walseth et al., 2018). More passive teaching methods, characterized by authoritative directives, can hinder athletes’ autonomy, leading to anxiety, boredom, and indiscipline (Reeve & Tseng, 2011). Such methods often focus on isolated, non-contextualized tasks that fail to engage students as active learners, diminishing their learning outcomes (Blomquist et al., 2001).\n\nConversely, active involvement methods encourage students to become creative, social learners who construct their own knowledge and identify areas for improvement (Dyson et al., 2004). These approaches emphasize the simultaneous development of technical skills, tactical understanding, and decision-making through real-game situations and problem-solving, exemplified by Teaching Games for Understanding (TGfU) and the Comprehensive Aquatic Method (MAC) (Moreno-Murcia & Ruiz, 2019).\n\nIntroduced by Moreno and Gutiérrez in 1998, the MAC is a constructivist approach that centers on student interests and needs, promoting autonomy and interaction. It employs play as a medium, with the educator fostering a positive, varied learning environment (Moreno-Murcia & González, 2022). This methodology encourages problem-solving and exploration in aquatic environments, developing knowledge, skills, and attitudes that contribute to student autonomy and personal growth (De Paula & Moreno-Murcia, 2018). Such models facilitate opportunities for all students to solve problems, make decisions, and demonstrate leadership (Metzler, 2011), equipping them with essential competencies for various life stages and contexts.\n\nUtilizing cognitive and constructivist methods in sport education can enhance information retention and enjoyment (Batez et al., 2021). This focus is crucial for increasing youth engagement in regular physical activity, especially considering that many students would opt out of physical education if given the choice, with over 50% of 10th and 11th graders expressing disinterest in the current curriculum (Ha, Johns & Shiu, 2003). Addressing challenges in identifying relevant PE content, actively engaging students, and building self-efficacy among educators and learners is essential for fostering health and social well-being through physical activity, with aquatic activities playing a critical role in drowning prevention.\n\n\nTeaching self-efficacy and teaching methods\n\nSelf-efficacy is a construct that has been analysed in the field of education in general and in specific contexts, such as school physical education and physical-sport activity (Balaguer et al., 1995) and is one of the most widely used theories in sport teaching and motor performance (Feltz, 1995). An extensive number of studies have accumulated over decades on the basis of Bandura’s (1986) social cognitive theory, especially in relation to people’s beliefs about their abilities, i.e., about self-efficacy evaluations and achievement behaviours in sport (Beauchamp et al., 2019). For example, the study by Moritz et al. (2000) found that self-efficacy is a consistent correlate of performance in sport. In this sense, the nature and direction of the efficacy-performance relationships differ depending on whether intrapersonal or interpersonal effects are considered (Beattie et al., 2016; Vancouver, 2018). That is, while athletes who display high self-efficacy beliefs in relation to others may be more likely to show better outcomes and performance, the nature of the efficacy-performance relationship may differ markedly when intra-individual effects are examined.\n\nSome studies (Vancouver & Purl, 2017) have shown that when task-related information and feedback are ambiguous, within-person effects tend to be negative, but when such information and feedback are unambiguous, within-person effects tend to be positive. When participants are provided with performance feedback, higher levels of self-efficacy are related to better subsequent performance, and when feedback is not available, the self-efficacy-performance relationship is negative (Beattie et al., 2016). This suggests that the way of teaching (teaching method) used by the teacher can help participants to achieve their present and subsequent achievements. The methodology implemented by the teacher can help to facilitate the construction of particular self-efficacy beliefs, as long as individuals have sufficient information on which to base their judgements of ability (Beauchamp et al., 2023) and in continuity self-efficacy allows the teacher to optimise and adjust the teaching method, but also the teacher-student, teacher-family interactions, cooperation between the elements of the educational team, decision-making and the atmosphere in the educational environment (Chacón, 2005; Ortan et al., 2021).\n\nTherefore, self-efficacy is based on a person’s beliefs about his or her own ability to plan, organise and execute the actions necessary to reach a certain achievement (Bandura, 1997). Specifically, in teaching action, this is an intrapersonal motivational variable that helps to increase students’ persistence, commitment and enthusiasm for practices (Skaalvik & Skaalvik, 2007). Beliefs about teaching effectiveness are constructed on the basis of two elements of the teaching-learning process: the task and the context (Chao et al., 2017). In this sense, the effective teacher should master different teaching methodologies and know how to adjust them to the needs of each context.\n\nEvidence indicates that, in general, teachers with higher self-efficacy are more likely to manage the classroom effectively (Tschannen-Moran & Woolfolk Hoy, 2007), to use more constructivist and higher quality instruction (Holzberger et al., 2013; Suprayogi et al., 2017), developing challenging approaches (Deemer, 2004), using creativity-focused instruction and comprehensive and meaningful learning (Deemer, 2004), encouraging learner autonomy and keeping learners motivated on task (Chao et al., 2017; Miller et al., 2017). Also, high self-efficacy values are associated with professionals who are more passionate about their teaching mission (Fernet et al., 2014), with greater control over their emotions, and even have less tendency to show anger or rage in front of their students’ behaviour (Shahzad & Naureen, 2017). It is very clear that the perception of teacher self-efficacy influences their professional practice with determining results in the learning processes of students (Pan, 2014) in the generality of educational processes where physical education is an important part, as it has a direct relationship with the promotion of active lifestyle habits and can influence the rate of personal aquatic competence from childhood through the practice of physical activity in the aquatic environment guided by professionals committed to their mission.\n\nIn order to analyse the methodologies chosen most frequently by aquatic educators, it is important to know their self-efficacy belief system (what I feel confident about doing, what I think the students’ role should be in class, how to act so that they learn, how to act to control/avoid indiscipline, etc.), as this is the main basis for the professional’s decision making when planning and directing the activity. There is a tendency to choose the activities in which one feels more confident to the detriment of those in which one feels less competent.\n\nTeacher self-efficacy is a critical factor that variably influences (positively and negatively) student performance, being more significant than class size, socio-economic status or the starting level with which the student arrives (Darling-Hammond & Youngs, 2002; Hindman & Stronge, 2009; Klassen & Tze, 2014; Staiger & Rockoff, 2010). There are numerous studies on self-efficacy in the context of Physical Education (Curran & Standage, 2017; De Meyer et al., 2016; Leo et al., 2020), however, there are few studies that relate teachers’ self-efficacy beliefs in practices and how they actually use these practices in their classroom (Poulou et al., 2019). Furthermore, we have not found research that verified the relationship between teaching methodologies and teacher self-efficacy in teaching in the aquatic environment.\n\nFor this reason, we consider answering the following questions related to the aquatic professionals’ belief system on teaching methodologies and self-efficacy from the teaching perspective: What is the aquatic professional’s perception of self-efficacy? What teaching methodologies does the most effective professional use?\n\nThe main objective of this study was to analyse the relationship between teaching methodologies, the comprehensive aquatic method and teaching self-efficacy, as well as to check which type of teaching methodology (cognitive, constructivist, behaviourist or laissez-faire) predicted the comprehensive aquatic method. Considering the results of the previously mentioned research, it is expected to find a predictive model where methodologies that actively involve students will positively predict the comprehensive aquatic method in aquatic educators. It is also expected that teacher self-efficacy will be predicted by the most learner-involving methodologies (constructive, cognitive and MAC).\n\n\nMethods\n\nA total of 607 aquatic educators (305 males and 302 females) aged between 18 and 61 years (M = 36.58, SD = 13.02) participated in this research and during february and april from 2024 the data analysis was done. The selection criteria for the sample were that they were at least 18 years old, with at least 6 months of teaching experience in the aquatic environment and that they were in possession of a qualification. By age, they were classified into three groups: under 25 years old (n = 162), between 25 and 40 years old (n = 197) and over 40 years old (n = 248). The educators’ training was as follows: graduates in Physical Activity and Sport Sciences (n = 147), Physical Education Teachers (n = 285), Sports Technicians (n = 102) and other qualifications (n = 73). According to the years of experience of the aquatic educators, they had the following values: less than 1 year (n = 75), between 1-5 years (n = 75), between 6-10 years (n = 277) and more than 10 years (n = 92). The aquatic educators who participated in the study were teaching students aged 0-6 years (n = 126), 7-12 years (n = 117), 13-18 years (n = 41), over 18 years (n = 36) and all ages (n = 287).\n\nThis study used three questionnaires from different authors and content that together address the issues in question, and their use has been possible with permission obtained from all authors of wich type of tool.\n\nComprehensive aquatic method (MAC). The scale validated by Castañón-Rubio et al. (2022) was used with permission obtained from the authors to use these tool, to measure the use of the comprehensive aquatic method in aquatic educators. This scale consisted of 26 items divided into 3 subscales as follows: a) way of teaching, consisting of 10 items (e.g. “In each class I evaluate the objectives”); b) game, consisting of 9 items (e.g. “I adapt the games taking into account the resource and characteristics of the aquatic installation”); c) the way of teaching, consisting of 10 items (e.g. “I offer possibilities of choice (groupings, materials, etc.) to participants.”). Responses were recorded on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). The internal consistency obtained for each of the dimensions was .93, .88, .87, respectively, and .91 for the global MAC, considering the three dimensions as one.\n\nTeaching methodologies. In order to analyse the teachers’ perception of the use of their methodology, the adaptation of the Teaching-Learning Methods Scale in Physical Education (TLMS-PE; Leo et al., 2020) was used with permission obtained from the authors. This questionnaire is composed of the introductory sentence (e.g., “In my classes…”), followed by 19 items organised in five dimensions: 5 items to assess the reproductive methodology (e.g., “I determine at all times the activity they should practice”), 5 items to assess productive methodology (e.g., “I make them look for and evaluate different answers and solutions to the tasks I set”), 6 items to assess the constructivist methodology (e.g., “I give participation to the students so that they can decide what they want to learn”) and 3 items to assess letting them do during the classes (e.g., “I spend time intervening at the beginning and end of the class distributing the material for them to play with”). The response format used is Likert-type with a 5-point response range from 1 (strongly disagree) to 5 (strongly agree). Reliability analysis showed how the items belonging to these variables were reliable for constructivist (.78), productive (.83), reproductive (.74) and laissez-faire (.70) methodology.\n\nTeacher self-efficacy. In order to assess teaching self-efficacy, was used an adapted version of the Teachers’ Sense of Efficacy Scale by Tschannen-Moran and Woolfolk (2001) with permission obtained from the authors to use these tool. The 12 items of this scale measure perceived teacher self-efficacy in three dimensions: a) perceived efficacy in optimising one’s own instruction (4 items); b) perceived efficacy in classroom management (4 items) and c) efficacy in involving students in learning (4 items). The reliability of the total scale was .92, while by dimensions it was .81, .86 and .81, respectively.\n\nThe present research has the approval of the relevant University Human Research Committee with the reference DCD.JMM.01.22, as well as all the scales used have obtained the respective permissions from their original authors. In order to carry out the data collection, different aquatic centres were contacted to request their collaboration in the study. The research team subsequently administered the questionnaire in an online format, which was answered voluntarily and anonymously. The researchers were also available to answer any questions that arose during the process of completing the questionnaire. The questionnaire took between 15-20 minutes to complete.\n\nDescriptive statistics (means and standard deviations) and bivariate correlations were calculated for all the variables under study. Cronbach’s alpha coefficient was used to determine the internal consistency of each of the dimensions. Also, the predictive power of the teaching methodologies on Comprehensive Aquatic Method (MAC) was tested by means of a stepwise multiple linear regression analysis. A significance level of p < .05 was used for the statistics obtained in the different analyses, which were carried out using the R Project for statics computing (R Core Team, 2023).\n\n\nResults\n\nThe most valued variable in the MAC was the autonomy-supportive teaching style, followed by the teaching style and play. In relation to teaching self-efficacy, the most important dimension was instruction, followed by strategies for involving students in learning and classroom management. Regarding teaching methodologies, cognitive methodologies were the most valued, followed by behavioural, constructivist and laissez-faire ( Table 1). Correlation analysis revealed the existence of a positive and significant relationship between all the dimensions (p < .01), except between the game and behaviourist dimensions (p < .01), which was negative and significant. No significant correlations were found between the dimensions way of teaching and interpersonal style and behavioural methodologies and letting do, and between play and letting do (p > .05).\n\nA stepwise linear regression analysis was undertaken to find out how the different methodologies used predicted the MAC. According to the last step in the linear regression analysis, the different methodologies used predicted MAC with an explained variance of 12% ( Table 2). The methodologies that positively predicted MAC were cognitive (ß = .29, p < .01) and constructivist (ß = .13, p < .05), while behaviourist (ß = -.12, p < .05) and let-do (ß = -.14, p < .05) methodologies predicted it negatively.\n\n* p < .05.\n\n** p < .01.\n\nA stepwise linear regression analysis was conducted to test which variables (teaching methodologies and MAC) best explained teaching self-efficacy. According to the last step in the linear regression analysis, cognitive (ß = .35, p < .01), behavioural (ß = .16, p < .01), and MAC (ß = .18, p < .01) methodologies positively predicted teaching self-efficacy with a total explained variance of 23% ( Table 3).\n\n* p < .05.\n\n** p < .01.\n\n\nDiscussion\n\nFull confidence in one’s own efficacy is needed in order to begin and sustain the effort to achieve success (Mone et al., 1995). Therefore, teacher self-efficacy may be essential for classroom success, as evidence (Miller et al., 2017) shows its relationship with teaching quality, student achievement and job satisfaction (Toropova et al., 2021). Most of the studies that analyse the relationships between different methodologies and general self-efficacy have focused on students and other contexts, so this research is a first approach to the study of these variables jointly on teachers in the aquatic education environment. With this in mind, the main objective of the study was to analyse the relationship between teaching methods, the MAC, and the teaching self-efficacy perceived by aquatic educators. In general terms, the results confirm our initial hypotheses, the MAC is more related to methodologies that actively involve students and is positively predicted by cognitive and constructivist methodologies. Furthermore, teacher self-efficacy is predicted by the methodologies that most actively involve the learner (constructivist, cognitive and MAC). These references are in line with Guskey’s (1988) study where the more effective teachers showed greater confidence and diversity of teaching strategies with creative and interesting pedagogical approaches in the classroom, contrary to the tendency of the less effective teachers to choose more traditional methods. The assessment of the development of water competence in physical education curricula can be considered as an innovative pedagogical proposal that more effective teachers are more inclined to consider and which we believe will have a positive effect on the future water competence index of society in general. Achieving this will depend on the high degree of flexibility needed to generate and adapt to new scenarios, where both teachers and pupils benefit (Shahzad & Naureen, 2017; Pan, 2014). This is essential, recognising the importance of benefiting pupils and teachers in the development and promotion of a more active and consequently healthier lifestyle.\n\nIn our study, all methods (constructivist, behavioural, cognitive, laissez-faire and MAC) have shown a positive relationship with the perception of self-efficacy in aquatic professionals. In general, science has identified that the use of more learner-centred methodologies generate a greater sense of teacher self-efficacy than the others, but with all of them it is possible to generate a sense of self-efficacy, although at different levels. Consequently, lower levels of self-efficacy are predictors of teacher burnout and stress (Dicke et al., 2014; Zhu et al., 2018) and lower student achievement (Sharma et al., 2012). Although teachers do not perceive different methods to be equally effective in all teaching situations (it depends on the task and context), it is the cognitive and constructivist methodologies that generate the most self-efficacy perceptions (Chao et al., 2017; Miller et al., 2017; Suprayogi et al., 2017). A constructivist view sees learning as a process of adapting and fitting into an ever-changing world and the aquatic environment, in its broadest expression, something is learned beyond what is practised in a pool or controlled environment. Interaction with the aquatic environment occurs through neuroception, perception, motor action and senses, so we build through the perception that the body gets from the experience (Light, 2008). In this sense and analysing the strong correlation of MAC with these methodologies focused on the students (for their autonomy and transfer of competences) and their needs, it is possible to affirm that MAC, due to its proximity to cognitivist and constructivist methodologies, when used, teachers will feel more self-effective and well succeeded in their role of contributing to the development of water competences and promoting students’ intrinsic motivation for physical activity through water activities.\n\nA dualistic view of the human being as mind and body (separation of self and action) is still common from a social point of view, and in this sense, following the approaches of behaviourist methodologies, the emphasis is still exclusively on the use of feedback and reward systems to alter and modify behaviour. But as Light (2008) points out, in a holistic view, the body and sensation are equally important in learning. So for lifelong use, the choice of the methodology to be used for better learning and retention will depend on the content to be covered, the age of the learner, their degree of autonomy and the effects expected.\n\nThere are several reasons that may explain the use of certain teaching methodologies, such as, for example, the development of motor skills and the improvement of sport-specific skills (Dudley et al. 2011; Hardman, 2008). There is often a tendency to use more behavioural teaching styles designed to help students develop correct technique while providing maximum practice time (Chatoupis & Vagenas, 2017; Goldberger, 1984, 1992), but teaching motivation must go beyond the intention of developing motor competence in participants or teaching competitive sporting activities (Chatoupis, 2018). It is not only about influencing children and young people in a certain content or set of contents focused on how to do, but that this perception of teaching self-efficacy can extrapolate its scope to the development of personal and social skills (areas of to know and to be, individually and in groups), through active learning on the part of the students, involved in an attractive way in the process (Ledertoug and Paarup, 2021).\n\nWe interpret that the use of behaviourist models leading to a perception of teacher self-efficacy may be due to: (a) the need for the aquatic educator to guarantee the safety of the students, as the aquatic environment has a possible risk of drowning built into it; (b) by tradition, as they have historically learnt this in their sports training centres and have not had the possibility of learning about other more efficient models; (c) by the pattern followed by technical models centred on sporting skill, which emphasise knowing how to do and reproduce, where deciding or thinking is not a necessity.\n\nIn the light of the contributions of this study, it is important to emphasise the role played by teachers in the design of their classes. In general, teachers feel more effective when their methodologies involve active learning, making students the protagonists of the process, giving them responsibility and autonomy, encouraging their creativity instead of meaningless memorisation, and teaching them to think in order to successfully solve the problems they face. But according to the study by Lubans et al. (2017) they are not reaching their potential and in order for the sessions to have a greater effect on the level of physical activity and physical literacy of young people it is essential to consider the quality of the tasks and for that it is important to design tasks with methodologies that actively involve the learner, in order to get the learner to focus more on mastery. This would be possible by giving more importance to aspects of self-improvement and learning, contributing to a perception of personal progress in a more effective way, feeling autonomous, competent and assuming a modifiable belief in their ability. These factors will allow them to overcome intrinsically motivated tasks, resulting in a positive psychological balance that can generate greater enjoyment and less boredom on the part of the students, as the enjoyment experienced in classes can be an important variable for greater learning. Extending the traditional to do approach into to know and to be may be one of the possible and decisive strategies, since in order to learn the brain needs to be excited and validated as meaningful. In terms of interaction with the aquatic environment, the development of this kind of knowledge is fundamental to make transfers of knowledge from educational environments to real environments more probable. The role of aquatic education as an integral part of school physical education can clearly make a difference, as it would imply learning by professionals who are aware, committed and competent about their mission.\n\nDespite the strengths of the study, there are a number of limitations to be taken into account when interpreting the results. Firstly, the teaching-learning methodologies are assessed from the point of view of the teacher and not the students, which may not reflect the true methodology used. Secondly, being a correlational study, the results do not indicate the existence of a cause-effect relationship between the variables considered. In relation to future prospects, it would be interesting to analyse the effect of the different methodologies in an intervention and to check whether the relationship presented in this study is confirmed in practice. In addition, it could be relevant to establish experimental studies with different groups with different methodologies and to analyse the benefits or consequences of each of them. Given the potential of self-efficacy beliefs to both enhance and impair performance, future research on self-efficacy could assess associations within individuals by analysing high quality feedback or information related to task performance and the methodology that has been used to generate goal achievement.\n\nThe intention professional who teaches aquatic education, independent of the educational setting, is that their students learn as much as possible regardless of the methodology they use. Their decisions are based on personal beliefs built up over time and influenced by some learning theories, which are rarely questioned (Rink, 2001). As the study by Toropova et al. (2021) indicates, this perception of self-efficacy varies with years of experience, being lower in less experienced professionals and declining in pre-retirement teachers.\n\nThis has been building cultural behaviours in the teaching methodology of the teacher in the aquatic context, which we can partly see reflected in this first study. In the search for true learning, evidence is needed in this regard, and it is challenging for trainees to implement more constructivist perspectives (Rovegno, 1998), as the starting point is to consciously question beliefs and relate them to the assumptions of learning (Davis & Sumara, 2003). It is necessary to understand learning theory and be aware of personal beliefs about the assumptions of what it means to be “‘water competent’” (Fonseca-Pinto & Moreno-Murcia, 2023). In this way, aquatic educators’ decisions should be adapted to the needs of the learner and the context.\n\n\nPedagogical implications\n\nOne of the main approaches to combat physical inactivity emphasises the need to improve the quality of activities, making them highly active and engaging (Hills et al., 2015). To encourage lifelong physical activity, counteracting current levels of inactivity, it is crucial to raise the levels of intrinsic motivation of practitioners. A multi-sectoral and multi-systemic approach is recommended, where both in-school and out-of-school programmes promote physical activity even outside the school environment (Lubans et al., 2017). However, in reality, the full potential of these programmes has not been fully realised. What are the possible contributions of this study?\n\nAware that there is still much to explore, given that the evidence is limited from both teacher and student perspectives, and that there is a two-way relationship that should not be neglected, this study presents cross-cutting aspects to other published studies, reinforcing the idea that these results can have direct implications for the teaching function, either in the field of school physical education, sports or extracurricular physical activities.\n\nIn this study, a relationship is observed between teaching methodologies and the level of self-efficacy perceived by the teacher. Cognitive and constructivist methodologies are the ones that best explain teacher self-efficacy. Although it is possible that teachers perceive themselves to be self-efficacious with all teaching methodologies, it is noteworthy that the values are higher when predominantly cognitivist and constructivist methodologies are chosen. There is a strong relationship between teacher self-efficacy, student self-efficacy, learning outcomes, job satisfaction and retention in the teaching career, indicating that teachers who wish to feel more effective should predominantly opt for these practices. However, it is important to note that the choice of teaching methodology is influenced by context, timing and learner needs.\n\nHigher teacher self-efficacy and the flexibility to manage the class with different methodologies and strategies allow for active student participation during the learning process, with positive effects on student motivation and learning climate (Pan, 2014). We recommend that future studies assess levels of personal motivation, enjoyment of physical activity in general or in specific sports, the influence of student motivation in the subject of physical education, and the teacher behaviours that most influence students’ intrinsic motivation to consider an active life by practising aquatic activities throughout life.\n\nAccording to the MAC methodology, the most highly valued variable was the teaching style of supporting autonomy and play. These teaching strategies are directly related to cognitivist and constructivist methodologies, also associated with higher values of perceived teacher self-efficacy. In summary, if the teacher seeks a greater positive impact on their students from an ecological and holistic perspective of pedagogy, and wishes to feel more self-effective, they should choose MAC as a methodology that is present and active in their teaching role.\n\nThere is no infallible method, but there is the ability to adjust methodologies to the circumstances. The MAC, as an example of a constructivist methodology, together with cognitivist and even, in some cases, behaviourist methodologies, can fulfil the function of the learning moment considering the student as the protagonist. To achieve this, lessons should be oriented with an educational and competence development objective, considering equally important to know, to do, know and to be Ledertoug and Paarup (2021), with an emphasis on aquatic activities due to the effect they can have on drowning prevention. It is crucial that the practitioner, whether in the context of school, sports or extracurricular activities, considers these indications because of the importance of decision-making and knowledge transfer to other settings. This transfer perspective also considers the lifelong practice of physical activity, which is essential to maintain high levels of personal water competence when aquatic activities are part of a more active lifestyle.\n\nIn addition to what is considered in this study and based on the evidence presented, we highlight that the perception of self-efficacy varies according to years of experience (Toropova et al., 2021). It is important to value specialised and highly complex continuous training to deepen knowledge about teaching and learning in the educational context (Catalano et al., 2020). The specificity of physical education, and in particular the protective role of water competence in drowning prevention, underlines the importance of this development in teachers’ professional and personal development.\n\nGiven that teacher self-efficacy is key to both professional motivation and emotional self-regulation of teachers, high levels of self-efficacy will positively influence the reduction of the likelihood of burnout processes (Ortan et al., 2021), thus preserving the physical, emotional and mental health of the professional, and directly benefiting the learner and learning.\n\n\nConclusions\n\nLevels of self-efficacy influence professional satisfaction, teacher physical, mental and emotional health, as well as student learning. Because of the positive and transversal impact that teaching intervention in school physical education classes or as a physical activity (extracurricular practice) can have on the personal water competence index, it is important to ensure high levels of teacher self-efficacy in aquatic education. All methods can generate a feeling of self-efficacy in teachers despite having different results, with the methodologies that involve students more actively (cognitivist and constructivist) being those that generate a greater feeling of self-efficacy in teachers, so is recommended that professional give preference to these methodologies. MAC is a method that is more closely related to methodologies focused on active student participation and, consequently, it is a method that generates a high perception of self-efficacy in teachers. And since the personal water competence index is socially important, we recommend, based on the data obtained, that MAC be considered a privileged methodological approach for promoting active lifestyle habits throughout life.\n\nThis study is part of a doctoral thesis organised into three parts related to aquatic competence and teaching methodologies. Specifically, this study addresses the issue of teaching methodologies in aquatic activities and the perception of self-efficacy by aquatic professionals. The University’s Ethics Committee has had access to the study project as a whole, which has been approved by the Miguel Hernández Ethical Committee with the DCD.JMM.01.22 code on 6 of February of 2024. All the participants in this study are adults and before started to answer the survey provided a written informed consent by agreeing to participate saying yes to the first question and respond to the complete questionnaire.",
"appendix": "Data availability\n\nFonseca-Pinto, R., & Moreno-Murcia, J.A. (2024b). Teaching self-efficacy and teaching methods in the aquatic environment. [Dataset]. Figshare. Online. http://doi.org/10.6084/m9.figshare.27310473\n\nThe project contains the following underlying data:\n\n• Data.xlsx. (anonymised answers to questionnaires)\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFonseca-Pinto, R., & Moreno-Murcia, J. A. (2024a). (Survey) Teaching Methods in Aquatic Education. [Dataset]. Figshare. Online. https://doi.org/10.6084/m9.figshare.27316242.v1\n\nThe project contains the following extended data:\n\n• Teaching methods in aquatic education (survey questionnaire).\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAinley J, Carstens R: Teaching and Learning International Survey (TALIS) Conceptual Framework. OECD Working Papers. 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Publisher Full Text\n\nLubans D, Lonsdale C, Cohen K, et al.: Framework for the design and delivery of organized physical activity sessions for children and adolescents: rationale and description of the ‘SAAFE’ teaching principles. Int. J. Behav. Nutr. Phys. Act. 2017; 14(24): 24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMetzler M: Instructional Models for Physical Education. 3ed ed.Scottsdale, AZ: Holcomb Hathaway; 2011.\n\nMiller A, Ramirez E, Murdock T: The influence of teachers’ self-efficacy on perceptions: Perceived teacher competence and respect and student effort and achieve- ment. Teach. Teach. Educ. 2017; 64: 260–269. Publisher Full Text\n\nMone M, Baker D, Jeffries F: Predictive validity and time dependency of self-efficacy, self-steem, personal goals, and academic performance. Educ. Psychol. Meas. 1995; 55: 716–727. Publisher Full Text\n\nMoreno-Murcia JA, González JM: La motivación en el Método Acuático Comprensivo.Moreno-Murcia JA, Albarracín A, De Paula L , editors. Aportes pedagógicos acuáticos. Sb editorial; 2022; pp. 97–104.\n\nMoreno-Murcia JA, Ruiz LM: Cómo lograr la competencia acuática. Sb Editorial; 2019.\n\nMoreno JA, Gutiérrez M: Bases metodológicas para la enseñanza de las actividades acuáticas educativas. Inde; 1998.\n\nMoritz S, Feltz D, Fahrbach K, et al.: The relation of self-efficacy measures to sport performance: a meta-analytic review. Res. Q. Exerc. Sport. 2000; 71: 280–294. PubMed Abstract | Publisher Full Text\n\nMosston M, Ashworth S: Teaching physical education. 5th ed.Boston: Benjamin Cummings; 2002.\n\nNuñez O, Oliver K: The collision of two worlds’: When a teacher-centered facilitator meets a student-centered pedagogy. Sport Educ. Soc. 2020; 26: 459–470. Publisher Full Text\n\nOrtan F, Simut C, Simut R: Self-Efficacy, Job Satisfaction and Teacher Well-Being in the K-12 Educational System. Int. J. Environ. Res. Public Health. 2021; 18(23): 1–32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPan Y: Relationships Among Teachers’ Self-Efficacy and Students’ Motivation, Atmosphere, and Satisfaction in Physical Education. J. Teach. Phys. Educ. 2014; 33: 68–92. Publisher Full Text\n\nPendergast D, Garvis S, Keogh J: Pre-service student-teacher self-efficacy beliefs: An insight into the making of teachers. Aust. J. Teach. Educ. 2011; 36(12): 46–57. Publisher Full Text\n\nPeng Y, Mao C: The Impact of Person–Job Fit on Job Satisfaction: The Mediator Role of Self Efficacy. Soc. Indic. Res. 2015; 121(3): 805–813. Publisher Full Text\n\nPoulou M, Reddy L, Dudek C: Relation of teacher self-efficacy and classroom practices: A preliminary investigation. Sch. Psychol. Int. 2019; 40(1): 25–48. Publisher Full Text\n\nR Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2023. Reference Source\n\nReeve J, Tseng C: Cortisol reactivity to a teacher’s motivating style: the biology of being controlled versus supporting autonomy. Motiv. Emot. 2011; 35: 63–74. Publisher Full Text\n\nRink J: Investigating the assumptions of pedagogy. J. Teach. Phys. Educ. 2001; 20: 112–128. Publisher Full Text\n\nRovegno I: The development of in-service teachers’ knowledge of a constructivist approach to physical education: Teaching beyond activities. Res. Q. Exerc. Sport. 1998; 69: 147–162. PubMed Abstract | Publisher Full Text\n\nSchwarzer R, Schmitz G, Tang C: Teacher burnout in Hong Kong and Germany: A cross-cultural validation of the maslach burnout inventory. Anxiety Stress Coping. 2000; 13(3): 309–326. Publisher Full Text\n\nSharma U, Loreman T, Forlin C: Measuring teacher efficacy to imple- ment inclusive practices. J. Res. Spec. Educ. Needs. 2012; 12(1): 12–21. Publisher Full Text\n\nShahzad K, Naureen S: Impact of Teacher Self-Efficacy on Secondary School Stufents Academic Achivement. Journal of Education and Educational Development. 2017; 4(1): 48–72. Publisher Full Text\n\nSkaalvik E, Skaalvik S: Dimensions of teacher self-efficacy and relations with strain factors, perceived collective teacher efficacy, and teacher burnout. J. Educ. Psychol. 2007; 99: 611–625. Publisher Full Text\n\nStaiger D, Rockoff J: Searching for effective teachers with imperfect information. J. Econ. Perspect. 2010; 24: 97–118. Publisher Full Text\n\nSuprayogi M, Valcke M, Godwin R: Teachers and their implementation of differentiated instruction in the classroom. Teach. Teach. Educ. 2017; 67: 291–301. Publisher Full Text\n\nToropova A, Myrberg E, Johansson S: Teacher job satisfaction: the importance of school working conditions and teacher characteristics. Educ. Rev. 2021; 73: 71–97. Publisher Full Text\n\nTschannen-Moran M, Woolfolk Hoy A: The differential antecedents of self- efficacy beliefs of novice and experienced teachers. Teach. Teach. Educ. 2007; 23(6): 944–956. Publisher Full Text\n\nTschannen-Moran M, Woolfolk Hoy A: Teacher efficacy: capturing an elusive construct. Teach. Teach. Educ. 2001; 17: 783–805. Publisher Full Text\n\nVancouver JB: Self-efficacy’s role in unifying self-regulation theories.Elliot AJ, editor. Advances in Motivational Science. Vol. 5. . Elsevier; 2018; pp. 203–230. Publisher Full Text\n\nVancouver JB, Purl J: A computational model of self-efficacy’s various effects on performance: moving the debate forward. J. Appl. Psychol. 2017; 102(4): 599–616. PubMed Abstract | Publisher Full Text\n\nWalseth K, Engebretsen B, Elvebakk L: Meaningful experiences in PE for all students: An activist research approach. Phys. Educ. Sport Pedagog. 2018; 23: 235–249. Publisher Full Text\n\nWoolfolk AE: Educational psychology. 7th ed.Boston: Allyn & Baker; 1998.\n\nZakariya Y: Effects of school climate and teacher self- efficacy on job satisfaction of mostly STEM teachers: a structural multigroup invariance approach. Int. J. STEM Educ. 2020; 7(10). Publisher Full Text\n\nZhu M, Liu Q, Fu Y, et al.: The relationship between teacher self-concept, teacher efficacy and burnout. Teach. Teach. 2018; 24(7): 788–801. Publisher Full Text"
}
|
[
{
"id": "341216",
"date": "09 Dec 2024",
"name": "Qi Tian",
"expertise": [
"Reviewer Expertise Educational psychology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper explores the relationship between teachers' self-efficacy and teaching methods through an extensive review of the literature. The conclusions drawn from the study are credible and provide valuable insights for enhancing both teachers’self-efficacy and their teaching practices. However, the article has two notable issues that need to be addressed: firstly, Insufficient Recent Literature: The paper cites a limited amount of literature from the past five years, comprising only 17.2% (15 out of 87) of the total references. This raises concerns about the relevance of the supporting evidence to current teaching contexts. Secondly, Statistical Scoring Conversion: The teacher self-efficacy scale differs from the other two scales in that it is not based on a 5-point scale. The article does not provide a clear explanation of how the scores from this scale were converted for statistical analysis, which could affect the reliability of the findings. To address these concerns, it is recommended that the authors update their references to include more recent studies, particularly from the last five years, to ensure the literature review reflects current trends and developments. Additionally, a detailed description of the methodology used for converting the teacher self-efficacy scores into a format compatible with statistical analysis should be included. These revisions will enhance the article's rigor and comprehensiveness. Suggestion: With these improvements, the article can be revised and considered for approval.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "341212",
"date": "14 Dec 2024",
"name": "Carolina Burnay",
"expertise": [
"Reviewer Expertise Child Motor Development."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article investigates the relationship between teaching methodologies and self-efficacy in aquatic educators. Key findings include:\nConstructivist and cognitive approaches, which emphasize active student participation, are most effective in enhancing teacher self-efficacy. The Comprehensive Aquatic Method (MAC), rooted in constructivist approach, is also positively linked to teacher self-efficacy. Behaviorist approach and laissez-faire methodologies are less effective in building teacher self-efficacy.\nBased on responses from 607 aquatic educators, the authors report that active, student-centered methodologies positively correlated with teacher self-efficacy, while passive approaches showed weaker associations. The study advocates for adopting cognitive and constructivist teaching approaches, more specifically, the MAC methodology, in aquatic education to improve teacher confidence and encourage healthier, more active lifestyles among students.\nHowever, some areas would benefit from further explanation or clarification.\n1. The authors reference developmental and learning theories such as constructivism, cognitivism, and behaviorism, treating them as though they were teaching methodologies. Teaching methodologies, like the cited MAC, can be developed using strategies underpinned by these theories. However, it is important to note that constructivism, cognitivism, and behaviorism are theoretical frameworks, not methodologies. By conflating these theories with methodologies, the authors claim to be investigating which methodology promotes higher levels of self-efficacy in teachers. This distinction between theories and methodologies should be clarified to ensure accuracy and alignment with the study's objectives.\n2. It is unclear which methodologies the authors are analyzing in relation to teachers' self-efficacy. In the Introduction (Teaching Methodologies) and Methodologies sections, the authors refer to:\nReproductive methodology – teacher direct approach Productive/learner centered methodology – problem solving, underpinned by the constructivist theory Constructivist methodology - active participation, enabling students to solve problems with teacher support Laissez-faire - teacher only organizes equipment and manages time and space without engaging with students during activities\nBut in the last paragraph of Introduction and in the Results sessions, when stating the main goals of the study, the authors refer to:\ncognitive, constructivist, behaviourist laissez-faire\nTo improve clarity and consistency, it is crucial to explicitly define the variables under analysis and use the same terms consistently throughout the manuscript. This alignment will help avoid confusion and ensure the study's findings are clearly communicated.\n3. While the Comprehensive Aquatic Method (MAC) is highlighted as effective, the manuscript provides limited quantitative comparisons between MAC and other methodologies. The authors describe the MAC as “a constructivist approach that centers on student interests and needs.” However, the results suggest that MAC methodology promotes higher self-efficacy in teachers than constructivist methodologies. This creates confusion regarding the definition and distinction of teaching methodologies, which requires clearer explanation and better conceptual alignment.\n4. In the Methods/Measures section, the authors mention that three questionnaires were used, but only one is available online. Additionally, in the last sentence of the Procedures section, the authors refer to “the questionnaire,” making it unclear whether participants were asked to complete three separate questionnaires or a single questionnaire that combines questions from the three mentioned in the Methods/Measures section. This ambiguity needs clarification to ensure the methodology is fully understood.\nTherefore, while the study provides valuable insights into the relationship between teaching methodologies and self-efficacy in aquatic education, addressing the identified issues of conceptual clarity, methodological consistency, and writing quality would significantly enhance the manuscript's overall impact and readability.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "341215",
"date": "18 Dec 2024",
"name": "Ana Rita Matias",
"expertise": [
"Reviewer Expertise Aquatic therapy",
"child development",
"learning development"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors, Thank you for submitting to the F1000Research such an interesting manuscript. Generally, some concepts need to be clarified, and also some English parts should be reviewed. After a careful reading, I have a few questions and suggestions, which I hope will help to improve your manuscript.\nABSTRACT BACKGROUND\nI suggest rewriting the following paragraph: “In turn, teaching methodologies influence motor learning, as well as psychological, cognitive and social learning, with different impacts on human development and learning retention, levels of intrinsic motivation and continuity of practice in order to support a healthy lifestyle.” Suggestion: Teaching methodologies influence learning, human development, motivation levels and, consequently, continuity of practice in favour of a healthy lifestyle. “… aquatic literacy is an integral part of physical literacy and the only possibility of being more able to interact with this environment.? – This sentence's meaning is unclear. At the end of this section, the two main objectives should be pointed out: 1. Assess the professionals' self-efficacy and 2) identify the methodology used by teachers who perceive themselves as most effective. These objectives should be aligned with the research questions on page 5 (5th paragraph).\nMETHODS MAC abbreviation should be introduced the first time it is mentioned.\nCONCLUSIONS The abstract should be aligned with the background, methods, and conclusions.\n\nINTRODUCTION P.3 “Healthy variability in teaching” does not clearly explain the meaning of this concept. It probably could be replaced by “There are different approaches regarding the interaction between teacher and student…”\nP.4 3rd paragraph “athletes” - It is suggested to use the same word throughout the text: student, subjects, athletes…\n6th paragraph “…especially considering that many students would opt out of physical education if given the choice, with over 50% of 10th and 11th graders expressing disinterest in the current curriculum” - This sentence's meaning is partly unclear.\n“…used by the teacher can help participants to achieve their present and subsequent achievements.” – This sentence's meaning is partly unclear.\nP.5 6th paragraph This paragraph should be rewritten to keep the goal of this study simple.\nMEASURES The authors should mention in which county the questionnaires were administrated and whether they needed to be translated.\nTeaching-Learning Methods Scale in Physical Education: The authors mention five dimensions but only present four.\nDISCUSSION It seems that all statistical procedures were correctly chosen.\n_________________\nFINAL REMARKS Despite being an article with a pertinent theme for the field, it needs some improvement. Apart from the above-mentioned suggestions, I suggest removing the data relating to the application of the MAC instrument. This study should focus on two objectives: 1) assessing teachers' perceived self-efficacy by applying the Teachers’ Sense of Efficacy Scale and 2) identifying which methodology is used by teachers who perceive themselves to be more effective, using the TLMS-PE.\nMAC’s data should be integrated into a second article.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1363
|
https://f1000research.com/articles/13-1362/v1
|
14 Nov 24
|
{
"type": "Research Article",
"title": "The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes",
"authors": [
"Cosphiadi Irawan",
"Findy Prasetyawaty",
"Findy Prasetyawaty"
],
"abstract": "Background Understanding the demographics, tumor characteristics, genetic mutations, and immune scores in colorectal cancer (CRC) patients may aid in tailoring treatment and predicting survival.\n\nMethods This retrospective cohort study assessed clinical parameters, immune scores, and their relationship with survival in patients with CRC.\n\nResults The study included 74 patients, mean age 53.7 years, mostly male (53.3%) and aged 41-70 (77.3%). Common comorbidities included cardiovascular diseases (29.3%) and hypertension (21.3%). Adenocarcinoma (74%) primarily affects the colon (73%). KRAS mutations and Microsatellite instability-High (MSI-H)/deficient mismatch repair (dMMR) were found in 1.3% and 16% of patients, respectively. Stage IV (77.3%) and liver metastases (52.7%) were prevalent. Immune score was influenced by cancer stage (p = 0.04) and metastasis (p=0.05). The immune score was not associated with survival (p = 0.181). Patients with comorbidities had lower one- (p = 0.027) and two-year survival rates (p = 0.037) survival rates. Cardiovascular comorbidities negatively impacted one-year survival (p = 0.047) and two-year survival (p = 0.037). The mean survival time was shorter for males (2.047±0.288 vs. 2.781±0.195 years, p = 0.041), patients with comorbidities (1.772±0.371 vs. 2.702±0.188 years, p = 0.017), and cardiovascular comorbidities (1.558±0.316 vs. 2.685±0.207 years, p = 0.038). Comorbidities (unadjusted hazard ratio [HR] 2.948, p = 0.023) and cardiovascular comorbidities (unadjusted HR 2.695, p = 0.046) were initially associated with survival but lost significance after adjusting for confounding variables.\n\nConclusions This study provides insights into CRC patient demographics and their interplay with the immune score and survival.",
"keywords": [
"colorectal cancer",
"demographics",
"tumor characteristics",
"immune score",
"survival"
],
"content": "1. Introduction\n\nAccording to GLOBOCAN 2020, colorectal cancer (CRC) stands as the third most predominant cancer globally, adding 10% of new cases in 2020, totalling over 1.9 million instances. Despite its ranking, CRC ranks second in terms of mortality rate, claiming 935,000 lives in 2020. It primarily affects the colon and the rectum. Geographic disparities in incidence and mortality rates are notable, with Europe and Australia/New Zealand reporting the highest incidence rates, whereas Eastern Europe experienced the highest mortality rates. Incidence rates are approximately four times higher in fully developed countries than in transitioning nations, although mortality rates exhibit less variability owing to increased fatalities in transitioning countries.1\n\nCRC often remains asymptomatic until its advanced stages, but its frequent symptoms include diarrhea, constipation, bloody stools, abdominal discomfort, unexplained weight loss, fatigue, and iron deficiency. Generally, affecting people over the age of 50 years, risk factors comprise a family history of CRC, Lynch syndrome, familial adenomatous polyposis (FAP), previous CRC diagnosis, or certain types of polyps. Lifestyle choices, such as eating habits rich in processed meats, low fruit and vegetable intake, smoking, obesity, sedentary behavior, and excessive alcohol consumption, further elevate the risk. This underscores the importance of adopting a healthy lifestyle and undergoing regular screenings, particularly for individuals over 50 years old or with a family history, to mitigate CRC risk.1\n\nUnderstanding the demographics of patients with CRC is crucial for identifying high-risk individuals and customizing screening and prevention strategies. Furthermore, delving into histopathology, tumor staging, location, and metastasis offers valuable insights for treatment planning and prognosis in CRC cases. Additionally, investigating genetic mutations in KRAS, NRAS, and BRAF is essential for guiding targeted therapy administration, predicting treatment responses, and determining prognosis.2 Assessing the prevalence of Microsatellite Instability-High (MSI-H)/Deficient Mismatch Repair (dMMR) or Microsatellite Stable (MSS)/Proficient Mismatch Repair (pMMR) is crucial for predicting responses to immunotherapy and prognosis.3 Understanding the percentage of patients receiving surgical treatment, targeted therapy, chemotherapy, and immunotherapy is essential for identifying areas in which therapeutic approaches can be improved.\n\nThe American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system is the primary method for classifying CRC, but lacks immune-based parameters, despite the known impact of the immune system on patient survival. However, the most up-to-date edition of Digestive System Tumors by the WHO emphasizes the importance of immune response in CRC diagnosis, highlighting the prognostic power of the immune score assay.4 This standardized scoring system, determined by the concentration of CD3+ and CD8+ T cells in both the tumor core and the surrounding invasive margin, offers a more clinically significant prognostic value than TNM staging alone.5 It helps estimate recurrence risk, guide treatment decisions, and assess responses to immunotherapies.6 Immune score may aid in selecting patients for adjuvant chemotherapy, identifying candidates for neoadjuvant therapy, and predicting outcomes more accurately.7 Notably, it categorizes patients into prognostic groups, indicating their risk of relapse and offering the potential for tailored treatment strategies in patients with CRC.8\n\nThe objective of this study was to investigate the demographic and clinical characteristics of CRC patients, including age, sex, body mass index (BMI), comorbidities, tumor location, tumor side, KRAS, NRAS, BRAF mutation status, microsatellite instability, immune score, disease stage, presence of metastasis, and targeted therapy use. Additionally, this study aimed to investigate the relationship between patient characteristics and immune scores, as well as patient characteristics and survival.\n\n\n2. Methods\n\nThis study was carried out at a tertiary care cancer facility, utilizing data from the Siloam Hospital database spanning 2020-2022. The dataset encompassed demographics, histopathology, tumor characteristics, staging, mutation status, treatment, comorbidities, and metastasis details. The study included adult patients (aged 18 years or older) with a confirmed diagnosis of CRC, with available clinical data from 2020 to 2022, and information on immune score and/or survival outcomes. Patients with other cancers or incomplete treatment records from outside the study period or different institutions were excluded. All CRC patients diagnosed and treated at the hospital between 2020 and 2022 were considered for inclusion. Given the limited number of CRC patients (n=75) during this period, all eligible patients who met the inclusion criteria were selected. The predefined follow-up period for the study was 3 years from the date of diagnosis or initiation of treatment. Survival outcomes were tracked through medical records, with regular follow-up visits documented in the hospital database. CRC diagnosis was confirmed via biopsy and histopathology with staging based on the American Joint Committee on Cancer (AJCC) Staging System 8th edition. KRAS, NRAS, and BRAF mutations were identified using polymerase chain reaction (PCR). To assess the Immunoscore, two consecutive slides from formalin-fixed, paraffin-embedded tumor samples were stained with anti-CD3 and anti-CD8 antibodies and counterstained with hematoxylin. The slides were digitized and specialized software was used to measure the abundance of CD3+ and CD8+ T cells in the tumor core (CT) and invasive margin (IM). The software identified the tissue, delineated the CT area, and displayed the IM. The classification of CT and IM was validated by a pathologist, and the software excluded necrotic or artifact areas. A histogram validates the staining quality and serves as an internal quality control. The intensity of CD3CT, CD3IM, CD8CT, and CD8IM cells were translated into percentiles, and the mean of these percentiles formed the immunoscore.6 The hospital's medical record team managed the database to ensure accurate and updated information. The study size was determined based on an expected 3-year overall survival (OS) rate of 75%, with a 10% margin of error and a 95% confidence level. Using a standard sample size calculation for proportions, the minimum required sample size was estimated to be 72 patients. Descriptive analysis, Kolmogorov-Smirnov tests for data normality, chi-square tests, Fisher’s Exact Test, and Kaplan-Meier Analysis were performed using SPSS software to explore the demographic and clinical characteristics of CRC patients. Cox regression was used to identify unadjusted and adjusted hazard ratios. This study was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia.\n\n\n3. Results\n\nA total of 74 patients with CRC were treated at Siloam Hospital between 2020-2022 ( Table 1). The mean age at diagnosis was 53.7 years with the majority (77.3%) being 41-70 years old, and a slight majority being male (53.3%). Body Mass Index (BMI) analysis revealed that 38.7% of patients had a normal weight (18.5–22.9 kg/m2) according to the WHO classification for Asia-Pacific. Notably, 33.3% were obese (≥25 kg/m2), 16% were underweight (<18.5 kg/m2), and 10.7% were overweight (23–24.9 kg/m2). Comorbidities were present in 36% of the patients, with cardiovascular diseases being the most prevalent (29.3%), and hypertension present in 21.3% of patients. Other cardiovascular diseases included diabetes mellitus type 2, coronary arterial disease, dyslipidemia, hypertensive heart disease, and arrhythmia. Additionally, a few patients had other comorbidities such as benign prostate hyperplasia, hepatitis B, and asthma.\n\nRegarding the site of CRC, the colon was the most commonly affected area, affecting 54 patients (73%), followed by the rectum (27.4%). Locations of CRC in the colon area were observed in the sigmoid colon (24.0%), rectosigmoid (21.3%), and descending colon (10.7%), ascending colon (6.7%), cecum (2.7%), hepatic flexure (1.3%), anal region (1.3%), transverse region (1.3%), and anorectal region (1.3%). Histopathological examination revealed that adenocarcinoma as the predominant subtype (74%), followed by mucinous adenocarcinoma (9.5%). Most tumors were located on the left side(86.7%). Of the left-sided tumors, 53.1% were male. The proportion of female and male patients with right-sided tumors was equal. Among left-sided CRC patients, 88.5% of them had exhibited adenocarcinoma and 11.5% had mucinous adenocarcinoma. Among right-sided CRC patients, 85.7% presented with adenocarcinoma, and only 14.3% had mucinous adenocarcinoma.\n\nKRAS mutations were detected in 1.3% of patients and absent in 68% of patients. NRAS mutations were absent in 66.7% of patients, and BRAF mutations were absent in 57.3% of cases. Overall, the prevalence was 16%, while MSS/pMMR prevalence was 37.3%. Notably, 33.3% of patients had a high immune score, 9.3% had an intermediate score, and 4% had a low score. Most patients were diagnosed with stage IV (77.3%), followed by 14.6% with stage III. The study found that 77.3% of patients had metastasis, primarily observed in the liver (52.7%), lungs (21.6%), and peritoneum (10,8%). Metastasis was also observed in the bone, ovarium, perineum, mesentery, pelvis, peritoneum, soft tissue perianal, bladder, omentum, uterus, vagina, bone, and para-aortic lymph nodes.\n\nMost participants underwent laparotomy resection of the tumor. Chemotherapy was administered to most of the patients. The most commonly used regimens were FOLFOXIRI, XELOX, and FOLFOX. Targeted therapy was administered to 42.7% of patients, while 50.7% did not receive targeted therapy. The targeted therapies included Bevacizumab, Cetuximab, Regorafenib, and Ramucirumab. Immunotherapy was not administered to any of the patients in this study.\n\nForty-three patients (58.1%) had KRAS wildtype and left-sided tumors. Among them, 25.6% received cetuximab as targeted therapy, while 51.2% of them did not receive targeted therapy. MSS/pMMR was present in 37.8% of patients, and all of them received chemotherapy.\n\nThere were significant relationships between cancer stage and immune score (p = 0.04), as well as between metastasis and immune score (p = 0.05). Age, sex, body mass index, comorbidities, cardiovascular comorbidities, tumor location, tumor side, microsatellite instability (MSI), and KRAS mutations were not significantly associated with immune score. A detailed breakdown of the relationship between clinical parameters and immune scores is provided in Table 2.\n\n* To determine the p-value, the immune score was classified into two categories: Low+Intermediate and High.\n\na Fisher’s Exact Test\n\nb Chi-Square Test For Independence.\n\nThe relationship between patient characteristics and survival indicated that overall comorbidities and cardiovascular comorbidities significantly affected the survival rates ( Table 3). For patients with comorbidities, the one-year survival rate was 56.3% compared with 87.5% in those without comorbidities (p = 0.027), and the two-year survival rate was 18.8% compared with 50.0% in those without comorbidities (p = 0.037). The mean survival time of patients exhibiting overall comorbidities was 1.772 ± 0.371 years, which was significantly lower than 2.702 ± 0.188 years) (p = 0.017). Similarly, patients with cardiovascular comorbidities had a one-year survival rate of 53.8% in comparison to 85.7% in those without cardiovascular comorbidities (p = 0.047), and a two-year survival rate of 15.4% compared to 48.6% in those without cardiovascular comorbidities (p = 0.037). The mean survival time of patients with cardiovascular comorbidities was 1.558 ± 0.316 years, which was significantly lower than 2.685 ± 0.207 years) (p = 0.038). Furthermore, survival was significantly linked to sex, with mean survival times of 2.047 ± 0.288 years for males and 2.781 ± 0.195 years for females (p = 0.041). There was no significant correlation between survival and variables, such as age, BMI, tumor location, tumor side, MSI, stage, metastasis, or immune score.\n\na Calculated by Fisher’s Exact Test and Chi-Square Test for Independence.\n\nb Calculated by log-rank test (Mantel-Cox).\n\nThe survival curve indicated that CRC patients with elevated immune scores exhibited a less steep survival curve compared to those with low or intermediate immune scores ( Figure 1), indicating a higher survival rate at higher immune scores. However, there was no significant association between immune score and survival (p = 0.181, Table 3).\n\nIn the analysis of unadjusted and adjusted hazard ratios (HR) for mortality using Cox regression, several patient characteristics that were significantly associated with survival were examined ( Table 4). The analysis also included the immune score and variables previously shown to significantly influence the immune score. For patients with comorbidities, the unadjusted HR for mortality was 2.948 (95% CI: 1.165-7.462, p = 0.023), indicating a significantly higher risk compared to those without comorbidities. However, this association was not significant after adjusting for other variables. Similarly, patients with cardiovascular comorbidities had an unadjusted HR of 2.695 (95% CI: 1.018-7.132, p = 0.046), but this significance was not observed in the adjusted analysis. No significant associations were found for sex, immune score, stage, or metastasis in either unadjusted or adjusted HR analyses. These findings suggest that, while comorbidities and cardiovascular comorbidities initially appear to influence mortality, their effects are not significant when other factors are considered simultaneously.\n\n* Adjusted HR for metastasis was not obtained because of multicollinearity with the stage variable.\n\n\n4. Discussion\n\nCRC is increasingly being diagnosed at earlier ages and more advanced stages, despite ongoing declines in overall incidence rates.9 The majority of our patients diagnosed with CRC were below 70 years old (90.7%), with the highest at 40-69 years old. On the other hand, Rawla et al. stated that the majority of CRC are likely to be diagnosed over 65 years of age.10 However, the number of cases has risen among people under 55 years old over the years, rising from 11% in 1995 to 20% in 2019.9 This is a reversal of the trend of disease diagnosis at earlier stages, as seen from 1995 to 2005.\n\nDespite the spread of early diagnosis in developed countries, the incidence of newly diagnosed cases were in advanced stages (60%) in 2019, whereas before the screening era, 52% of cases were diagnosed in advanced stages in the mid-2000s, and 57% in 1995.9 This is in line with our study, in which all of our CRC patients were diagnosed at stage IV (78.4%).\n\nThe surge in CRC cases among younger individuals and the detection of more advanced stages reflects lifestyle and dietary shifts. Attributes such as increased ingestion of animal-based foods, sedentary habits, and obesity are independently linked to CRC risk. Lifestyle habits such as smoking, alcohol consumption, and intake of processed or red meat also contribute to this risk.9 Conversely, diets rich in high-fiber foods, whole grains, dairy products, and calcium supplements are associated with a reduced risk of CRC.11\n\nNearly half of our patients were classified as overweight (12.2%) or obese (32.4%) according to the Asian-Pacific BMI standards. Obesity is associated with a higher risk of CRC.12–14 Obesity is caused by a positive energy imbalance, which is characterized by an overall increase in caloric intake and a reduction in physical activity due to a sedentary lifestyle, in addition to hereditary predisposition.\n\nA dose-response meta-analysis revealed that every 10 kg increase correlated with an 8% increase in CRC risk.15,16 Early life obesity predisposes individuals to a heightened risk of CRC in adulthood.12,15 This aligns with the existing literature highlighting elevated BMI (characterized by overweight and obesity) as a significant risk factor for CRC, although the precise molecular mechanisms remain elusive. Obesity triggers dysregulated lipid metabolism, altered adipokines and hormonal profiles, persistent inflammation, gut flora imbalances, and dysregulated bile acid equilibrium, all of which potentially fuel CRC carcinogenesis.17 Notably, obesity triggers ongoing low-level inflammation through proinflammatory and anti-inflammatory cytokines originating from adipose tissue, such as IL-6, TNF-α, and PAI-1.18 This chronic inflammation serves as a primary connection between obesity and the CRC tumor microenvironment,13 activating pathways that drive proliferation, migration, and metastasis.19,20\n\nAmong our patients, 35.1% had comorbidities. The most common comorbidity was cardiovascular disease (28.4%), with hypertension being the most prevalent (20.3%). Other comorbidities included diabetes mellitus type 2 (8.1%), coronary arterial disease (5.4%), dyslipidemia (2.7%), hypertensive heart disease (1.4%), and arrhythmia (1.4%). Our results align with information obtained from the South Asia Cancer Registry, which showed that the most prevalent comorbidities of CRC are hyperlipidemia, hypertension, and diabetes.21 CRC is typically prevalent in older individuals who often have chronic illnesses such as diabetes and cardiovascular diseases (CVDs).22 Comorbidity rates are notably elevated among CRC survivors, ranging from 46% to 62%,23,24 surpassing those of control patients without cancer, which range from 11% to 50%.25 Comorbidities exacerbate health challenges for cancer survivors, leading to increased symptom burden, reduced quality of life, elevated mortality rates, and heightened healthcare expenses compared with individuals without cancer.26 Therefore, it is essential to implement specific actions and strategies for managing CRC because the prevalence of comorbidities is high among patients with CRC.\n\nThe Indonesian national guidelines recommend screening for CRC based on individual risk, personal preferences, and access. For those at moderate risk, screening should commence at age 50, incorporating rectal examination and a range of diagnostic modalities, including yearly fecal tests, such as fecal occult blood test (FOBT) or fecal immunochemical test (FIT). Colonoscopy, flexible sigmoidoscopy, CT colonography, and double-contrast barium enema should all be performed every five years. Patients with a history of polyps in previous colonoscopy, previous family history of CRC, and patients with a diagnosis of Hereditary Nonpolyposis Colon Cancer (HNPCC), Familial Adenomatous Polyposis (FAP), or Inflammatory Bowel Disease (IBD) were considered at high risk and should be recommended for colonoscopy based on the determined interval or time.26 However, the CRC screening program in Indonesia has not been implemented across the entire population because of limited healthcare access and the lack of coverage for diagnostic procedures by the National Health Insurance for individuals with low to moderate risk. Primary prevention of CRC through screening remains key to reducing the burden of CRC. Screening of a large population cannot be achieved because of the significant cost of colonoscopy and other diagnostic procedures. Evidence suggests the use of guaiac fecal occult blood test (gFOBT) and fecal immunochemical tests as affordable and less invasive screening methods that can be implemented in Indonesia.1,27\n\nWe found that the majority of the patients were male (52.7%) slightly higher than females (47.3%). However, data from GLOBOCAN 2018 stated that the majority of CRC patients were male (1.5-fold higher than females).5 In 2020, the global CRC incidence rate in males was 1,065,960, which is higher than that in females at 865,630.28\n\nA higher prevalence of left-sided tumors (86.5%) was observed compared to right-sided tumors (10.8%),29 with tumor location playing a crucial role in disease progression, prognosis, and treatment strategies. Right-sided CRC, originating from the cecum, ascending colon, hepatic flexure, or transverse colon, exhibits distinct molecular characteristics and histology from left-sided CRC, which arises in the splenic flexure, descending colon, or sigmoid colon.29 Disparities between the two sides of the colon are evident across physiological, molecular, and therapeutic domains. Notably, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology underline variations in therapeutic responsiveness, particularly with EGFR inhibitors, such as cetuximab and panitumumab, which demonstrate greater efficacy as a first-line regimen for metastatic disease in left-sided CRC.30 Additionally, patients with tumors on the right side often present with advanced tumor stages, larger tumor sizes, and more frequently poorly differentiated tumors, along with higher rates of lymphovascular invasion compared to those with left-sided CRC.31 Systematic reviews and meta-analyses have associated right-sided CRC with poorer prognosis and decreased overall survival.32\n\nTumors on the right side frequently possess mutations in the DNA mismatch correction mechanism, particularly in the microsatellite unstable group (MSI), and typically manifest flat histology.29,33 Despite this, the majority of patients with right-sided CRC in our study presented with adenocarcinoma histology (88.5%). Conversely, left-sided tumors are characterized by genetic alterations within the chromosomal volatility pathway, implicating genes, such as p53, BRAF, PIK3CA, APC, and KRAS. Patients with left-sided CRC derive greater benefit from adjuvant chemotherapies, such as 5-fluorouracil (5-FU)-based regimens, and targeted therapies, such as anti-epidermal growth factor receptor (EGFR) therapy, which contribute to a more favorable prognosis. In contrast, right-sided CRCs often exhibit poor responses to chemotherapy, but show more encouraging outcomes with immunotherapies, likely attributable to the heightened antigenic burden of these tumors. Recognizing right- and left-sided tumors as separate entities and tailoring treatment regimens is crucial for maximizing therapy effectiveness.29,33\n\nColonoscopy screening facilitates early detection of left-sided CRC, particularly in the form of small adenomas. Right-sided CRC can still be detected in the early stages; however, it is more challenging than left-sided CRC tumors because of their flat morphology.34,35 Therefore, right-sided tumors are more frequently identified in later stages than LCRC tumors. The majority of our patients had left-sided CRC (88.5%), however a large proportion of them were diagnosed with a late stage of disease, with 78.4% at stage IV and 14.9% at stage III. Notably, metastasis was present in the majority of patients, accounting for 78.4%). This is reflected in the low screening rate and poor early diagnosis of patients. This should be addressed to reduce the morbidity, mortality, and cost of CRC patients in our region.\n\nThe liver (52.7%), lung (21.6%), and peritoneum (10.8%) were the predominant sites of metastasis in CRC cases, consistent with findings from the Surveillance, Epidemiology, and End Results (SEER) database, which highlights the liver as the primary distant metastatic site, followed by the lung, bone, and brain. Given its adjacency to the colorectum, the liver is the most common anatomical site for CRC metastasis.36\n\nDetermining the mutation status is crucial for prognosis and treatment options. Our data revealed that many patients did not have their mutation status evaluated, with only 70.3% checking for KRAS mutations, 66.2% for NRAS, 58.1% for BRAF, and 54% for MSI. The RAS and RAF protein families are key to signal transmission from growth factor receptors, promoting cell survival and proliferation. Overactivity of these pathways, mainly due to RAS and BRAF mutations, is common in various cancers. Women frequently develop right-sided colon cancer, which is typically linked to microsatellite instability and mutations in the BRAF gene. Conversely, men are more prone to left-sided colon cancer, which is often associated with chromosomal instability and KRAS gene mutations. Identifying KRAS, NRAS, and BRAF mutations is vital for determining patient eligibility for therapies such as panitumumab and cetuximab, as supported by clinical trials such as the PRIME study for panitumumab and the CRYSTAL study for cetuximab.37–39 Identifying mutations in KRAS, NRAS, and BRAF is crucial because the presence of these mutations results in a poor response to anti-EGFR therapy. Only 25.6% of patients with KRAS wildtype and left-sided tumors received cetuximab. The low utilization of cetuximab can be a result of several factors, including limited awareness, accessibility to targeted therapies, mutation testing, and its high cost. A significant number of patients (33.3%) had a high immune scores. However, no immunotherapy was administered to our patients because of the limited healthcare resources and high cost of the drug.\n\n4.2.1 Age and immune score\n\nThe investigation into the association between age and immune score in patients with CRC revealed no statistically significant association (p = 0.768). Aging is known to induce changes in the immune system, especially in CD8+ and CD4+ T cells. There are molecular expression changes and functional alterations in T cells associated with aging, such as decreased responsiveness to new antigens, deficient migration patterns, and accumulation of memory and regulatory T cells. Moreover, alterations occur in the manifestation of co-stimulatory signals, including CD27 and CD28, which play a crucial role in activating T cells, along with a simultaneous increase in inhibitory molecules such as PD-1 and CTLA4, resulting in T cell exhaustion.40 There are also sets of aging-related genes that are significantly activated in CRC tissues, predicting survival, severity, and the presence of immune cells within the tissue of CRC patients.41 Older patients exhibit lower expression of CD3+ and CD8+ T cells at the invasive tumor edge and lower immune scores.42 In breast cancer, the number of CD8+ cells weakly correlates inversely with patient age.43\n\nHowever, some studies have found that age is not a significant predictor of immune response in patients with CRC. Andric et al., who studied T cell subsets in patients with early onset CRC (aged <45 years) and average-onset CRC (aged 70-75 years) with left-sided colon and rectal locations, found no significant variances among the pair of groups concerning overall T cell infiltration, CD4+, CD8+, regulatory T cells, and γδ T cells. The expression of inflammatory mediators was also similar between the two groups.44 Ugai et al. found no difference in immune cell density between patients with early- and late-onset CRC.45 Lymph node ratio (LNR), a clinical hallmark denoting the immune reaction to colorectal tumors, is also strongly influenced by age.46\n\nDiscrepancies in these study findings could stem from variations in sample size,44,45 patient demographics, CRC heterogeneity, including location, stage, and molecular subtype, as well as differences in the measurement of immune parameters between studies. The fact that there is an escalating incidence of CRC in adults under 50 is still unknown47 and requires further research, including aspects of immune response parameters.\n\n4.2.2 Sex and immune score\n\nSex was not associated with the immune score (p = 0.138). Barbosa et al. found no significant difference in the infiltration of CD3+ (p = 0.303), FoxP3+ (0.296), and CD8+ (p = 0.529) cells at the edges of CRC tumors between males and females.48 Liu et al. reported similar findings for CD3+ (p = 0.254) and CD8+ (p = 0.714) cells.49 The proximity scores of T cells between female and male patients with CRC did not differ significantly (p = 0.65).50\n\nHowever, some studies have reported conflicting results. Ray et al. found that females had higher T cell infiltration, specifically CD8, CD4, and Th2 cells, as well as IL-10+ macrophages, whereas males had higher levels of inflammation-related chemokines and cytokines.51 Renman et al. concluded that higher total CD3+ and CD8+ scores were associated with the female sex.52\n\nThe role of sex in the immune response in CRC patients is associated with several factors, including hormonal influences (lower levels of estrogen and progesterone in postmenopausal women connected with an increased number of CD4+ T cells within the tumor tissue) and differences in gene expression related to immune responses such as GARP, which modulates Treg cells in the colon, as well as CD96 and CCL14, which are associated with T cell activity and survival. Sexual dimorphism in the CRC microenvironment tends to favor females over males.53\n\n4.2.3 Body mass index and immune score\n\nWith a p-value of 0.905, there was no notable correlation between the body mass index (BMI) and immune score. When examining patients with CRC categorized by high and low BMI, no significant disparities were observed in gene regulation within CD8+ cells.54 Hanyuda et al. discovered that lymphocytic response patterns (Crohn’s-like response, peritumoral response, intratumoral periglandular response, or tumor-infiltrating lymphocytes), overall lymphocytic ratings, and T cell density (CD3+, CD8+, CD45RO+, and FOXP3+) were not associated with BMI. Increased adiposity might be associated with an elevated risk of CRC, irrespective of the analyzed patterns of tumor lymphocytic infiltration.55\n\nOther studies have identified a connection between BMI and immune reactions in patients with CRC. Lavotshkin et al. determined that BMI exhibits an inverse relationship with CD3+ and CD8+ cells.56 Ugai et al. concluded that long-term average BMI correlated with the emergence of tumors with low CD15+CD33- cell density, but not with tumors exhibiting medium or high CD15+CD33- cell density.57\n\nObesity is known to increase the CRC risk by 2-3% for each incremental BMI unit.58 Obesity is presumed to foster tumor development by disturbing antitumor immune reactions and provoking T cell fatigue via leptin-induced PD-1 elevation.59,60 The relationship between immune response and the correlation between obesity and CRC should be further investigated.\n\n4.2.4 Comorbidities and immune score\n\nThere was no significant association between the existence or absence of comorbidities and the immune score (p = 0.362). Specifically, cardiovascular comorbidities were not associated with immune score (p = 0.267). Similar findings were obtained by Karjula et al. (p = 0.748) based on the Charlson Comorbidity Index (CCI).61 The risk of CRC increases with the presence of cardiovascular risk factors, such as obesity (RR 1.31), active smoking (RR 1.20), diabetes (RR 1.25), and hypertension (RR 1.07).62 The incidence of cardiovascular events, especially coronary heart disease, is higher in CRC patients within the first three years after diagnosis than in individuals without CRC.63 However, research examining the influence of comorbidities, including cardiovascular comorbidities, on immune response parameters in colorectal tumors remains limited.64\n\n4.2.5 Tumor location and immune score\n\nWith a p-value of 0.947, there was no significant association between tumor location and immune score. Consistent with this, the baseline characteristics of the study by Koelzer et al. found no difference in the intraepithelial and stromal CD8 density between left-sided colon, right-sided colon, and rectal tumors.65 Koelzer et al. found a non-significant link between CD8+ infiltrating the tumor and tumor location, namely, the colon and rectum (p = 0.355).66 However, tumor location may be a consideration when assessing the prognosis of CRC based on immune response parameters, as different immune cells are specific prognostic factors for tumors at specific locations. An elevated presence of CD8+ cells serves as a positive prognostic predictor for patients with right-sided colon tumors situated on the right side. FoxP3+ concentration is an advantageous prognostic factor only for rectal tumors, whereas CD3+ is a favorable prognostic factor for right-sided colon and rectal tumors.67\n\n4.2.6 Side and immune score\n\nThe results of this study indicated no discrepancy in the immune score between left- and right-sided CRC (p = 0.439). CD8+ infiltration is more abundant in colon cancer tumors residing on the right side,49,64 while NK cell concentration is more profuse in left-sided CRC. Alongside the higher CD8+ infiltration on the right side, there is higher immune activation, as evidenced by the cytotoxic activity score, antigen presentation machinery, interferon-γ signature, and CD8+ T-cell/Treg ratio. The activation of NK cells in left-sided CRC is associated with longer survival rates. These differences in immune cell infiltration indicate why patients with tumors located on the right side exhibit a more favorable response to anti-VEGF antibodies, whereas patients with tumors situated on the left side show a superior response to anti-EGFR antibodies.64 However, Guo et al. found conflicting results, where CD8+ expression at the invasive edge and immune score were inferior in right-sided tumors.68 Berntsson et al. also found denser CD8+ infiltration in left-sided tumors.67\n\nRight-sided CRC is attributed to a 14% less favorable prognosis and diminished survival rates in contrast to cancer on the left CRC, with a 4.2% higher mortality rate.42,69 Left-sided cancer tends to be diagnosed earlier, possibly because it can be more easily diagnosed with sigmoidoscopy or with clearer symptoms, such as rectal bleeding or changes in bowel habits.69 Perineural invasion and vascular emboli occur more frequently in right-sided cancers but are not associated with survival rates.42 Further research is needed on the differences in the immune microenvironment between left- and right-sided cancers, considering that these differences may explain differences in prognosis and response to therapy agents between right- and left-sided cancers.64\n\n4.2.6 MSI and immune score\n\nMSI was not associated with immune score (p = 0.238). This discovery diverges from previous research, which has indicated a link between MSI-high and immune score or heightened infiltration of cytotoxic lymphocytes, particularly CD8+.34,70–72 Mlecnik et al. noted that the abundance of intratumoral CD8+ cells tends to be greater in MSI-high tumors, both within the tumor’s core and at its invasive periphery, whereas the CD8+ cell abundance in the stroma remains similar.73\n\nMSI-high tumors frequently exhibit numerous intraepithelial T cells in response to neoantigen presentation on the cell surface, potentially contributing to the enhanced prognosis of patients with MSI.74 Immune score has been recognized as a more robust prognostic indicator than microsatellite instability status.73–75 Although the majority of patients with elevated immune scores also display MSI-high status, instances of high immune scores coupled with low MSI are not uncommon. In immunogenic MSI-low scenarios such as these, survival outcomes are more heavily influenced by the immune score rather than MSI status, as patients with elevated immune scores statistically exhibit prolonged survival compared to those with reduced immune scores, irrespective of their MSI status.74\n\n4.2.7 KRAS, NRAS, and BRAF mutations\n\nThere was no significant relationship between KRAS mutations and the immune score (p = 0.137). This aligns with Ogino et al., who identified no significant association between KRAS mutation status and T cell infiltration, although this study was limited to examining the density of specific T cell subsets.75 Similarly, Kwak et al. reported that KRAS mutations are not linked to immune scoring models.76 These findings suggest that while KRAS mutations contribute to an immunosuppressive TME, their impact on T cell infiltration may be nuanced and requires further investigation using comprehensive immune profiling techniques.\n\nHowever, there are studies that have found a significant association between KRAS mutations and immune scores. KRAS mutations are prevalent in various cancers, including CRC, and are associated with distinct immunological signatures in the TME. Research indicates that colorectal cancers with KRAS mutations frequently demonstrate diminished infiltration of cytotoxic T cells and Th1 cells compared to their wild-type counterparts.34,77,78 Additionally, CD4+ levels were lower in KRAS-mutant CRCs.79 Furthermore, KRAS activation promotes an immunosuppressive TME by upregulating regulatory T cells (Tregs) and impairing the function of cytotoxic CD8+ T cells.80 Mechanistically, mutant KRAS-expressing tumor cells release lactic acid, which sensitizes cytotoxic CD8+ T cells to apoptosis via NF-κB inhibition.77 NF-κB and T-cell receptor signaling are inhibited in mutant KRAS CRCs cells. The immunosuppressive tumor microenvironment (TME) promotes the transformation of CD4+ cells into Tregs and upregulates the expression of CXCL3, which aids in the migration of Tregs into the tumor core. KRAS also decreases MHC-I molecules, causing CD8+ cells to be unable to recognize tumor cells.77,80 This immunosuppressive milieu mediated by KRAS mutations renders tumors less responsive to immune checkpoint inhibitors (ICIs) and adoptive T-cell therapies.77\n\nIn this study, the association between immune score and mutations in NRAS and BRAF could not be determined because there were no cases of NRAS and BRAF mutations. Similar to KRAS mutations, NRAS mutations in CRC are associated with alterations in immune cell infiltration in the TME. CRCs harboring NRAS mutations exhibit significantly lower levels of CD4+ T cells than their wild-type equivalent.79 However, the specific impact of NRAS mutations on immunotherapy efficacy remains unclear and warrants further investigation. In contrast to KRAS mutations, BRAF-mutant CRCs display increased immune cell infiltration, particularly higher levels of PD-L1 expression and CD8+ T cell infiltration, regardless of MSI status.81 This immune-rich TME in BRAF-mutant tumors suggests a potential susceptibility to immunotherapy, including immune checkpoint blockade. Additionally, PD-L1 expression in CRC has been attributed to increased tumor-infiltrating lymphocytes and microsatellite instability, suggesting adaptive immune resistance.82\n\n4.2.7 Stage and immune score\n\nStage was significantly associated with the immune score (p = 0.040). Consistent findings were reported by Liu et al., who found significant correlations between CD3 and CD8 expression and the existence of metastasis in the lymph nodes as well as the III-IV TNM stage (p < 0.05).50 Moreover, CRC at later stages, including those with lymph node infiltration, exhibited significantly diminished infiltration by CD8+ cells (p = 0.00004).83 However, Irawan et al. revealed that the expression of CD8+ infiltrating the tumor did not differ significantly among stage I, II, III, and IV CRC (p = 0.390).66 Similarly, Fachruddin and Jeo discovered no significant correlation between the immune score and clinical TNM stage of CRC (p = 0.640).84\n\nStudies have indicated that in early-stage CRC (stages I-II), CD8+ TILs are highly prognostic, suggesting a favorable outcome.85 However, in metastatic CRC (stage IV), the impact of CD8+ TILs remains unclear. Saleh et al. examined the genetic activity of T cells across both stages of colorectal cancer, whether early or advanced. They found that CD8+ TILs from patients with advanced stages of CRC exhibited downregulation of genes linked to T-cell activation, migration, cell destruction, and adaptive immune response.86 This downregulation suggests that CD8+ TILs in late-stage disease may have a diminished ability to migrate to tumor locations, dysregulated activation, and restricted responses to tumors. Furthermore, the upregulation of genes linked to cellular reactions to oxygen deficiency in advanced stages might result in programmed cell death of T cells and heightened release of inhibitory cytokines, such as IL-10. This dysfunction of cytotoxic T cells in advanced CRC stages may be associated with T cell exhaustion and differentiation into CD8+ regulatory T cells (Tregs).86 In general, CD8+ TILs in later stages not only demonstrate dysregulated activation and effector functions but also exhibit a restricted capability to multiply and transform into memory T cells. Additionally, the prognostic significance of T-cell infiltration is affected by the expression of stromal cell-derived factor-1 (SDF-1).87\n\n4.2.8 Metastasis and immune score\n\nThere was a significant association between metastasis and immune score (p = 0.050). In CRC metastasis, immune score may vary.88 However, Mlecnik et al. found that the immune score serves as a prognostic indicator of metastatic spread.89 The presence of adaptive immunity and T cells has been linked to the prevention of premature metastatic infiltration.90 In CRC metastases, the densities of CD3 and CD8 were lower (p < 0.05). In distant metastasis, the density of CD8 was lower (p = 0.025).91 A lower density of CD8+ cells was positively correlated with lymph node metastasis (p = 0.042).92 CD8+ T cells play a pivotal role in stopping tumor growth and hindering cancer metastasis. They achieved this by directly identifying and destroying cancer cells using specific intracellular antigens. In cancer, the expression of genes that inhibit CD8+ cells, macrophages, CD4+, and TH1 increases, thus forming an immunological environment that supports tumor defense and metastasis.93\n\nThe findings of this study highlight the significant influence of comorbidities, particularly cardiovascular, on patient survival. Patients with comorbidities had significantly lower one- and two-year survival rates and mean survival times than those without. These results align with those of previous studies by Michalopoulou et al.94 and Pule et al.,95 which demonstrated that the presence of comorbidities negatively affected long-term survival and increased both CRC-specific and overall mortality. In particular, cardiovascular comorbidities significantly reduce survival rates. Janssen-Heijnen et al. reported increased mortality risk among older stage I or II colon cancer patients with cardiovascular disease.96 Gouverneur et al. noted that while cardiovascular comorbidities impacted cardiovascular safety, they did not significantly affect the overall survival of patients treated with bevacizumab.97 However, Cox regression analysis revealed that although comorbidities and cardiovascular comorbidities initially seemed to elevate the risk of mortality, their impact was not significant after accounting for other variables.\n\nRegarding sex differences, the study found that females had a significantly longer mean survival time than males. This observation is supported by several studies, including those by Ma et al.98 and Yang et al.,99 who found that females generally have better overall survival rates than males. However, it is important to note that other factors, such as tumor side and molecular characteristics, may also influence these outcomes, as highlighted by Baraibar et al.100 However, Cox regression analysis did not show a significant association between sex and mortality in either unadjusted or adjusted HR analyses.\n\nSurvival analysis showed that CRC patients with moderate and elevated immune scores exhibited a less steep survival curve than those with low immune scores, suggesting better survival rates with higher immune scores. Nonetheless, the correlation between immune score and survival was not statistically significant (p = 0.181).\n\nResearch on CRC patients with liver metastases demonstrated that individuals with a high immune score experienced much longer recurrence-free survival (RFS) than those with a low immune score, with medians of 21.4 months versus 8.7 months, respectively (p < 0.001). The 3-year RFS rate was notably higher at 42.4% for high immune scores than at 17.0% for low immune scores (p < 0.001). For overall survival (OS), patients with high immune scores did not reach the median OS, whereas those with low immune scores had a median OS of 28.7 months (p < 0.001). Furthermore, the 5-year OS rate was a significantly different, with 59.7% for high immune scores versus 25.9% for low immune scores (p < 0.001).101 Similarly, Li et al. revealed that high immune scores were significantly associated with better survival times (p = 0.048), with median survival at 101.4 months compared to 62.7 months for low immune scores.102\n\nThis study did not find a relationship between immune score and survival, likely due to all patients were in advanced stages (III or IV), with 77% in stage IV, both of which are associated with poor survival outcomes.103,104 Although some studies have suggested that the immune score is prognostic in metastatic CRC (stage IV), Lin et al. found it ineffective in predicting outcomes for colorectal liver metastases after hepatectomy.105 The immune score is currently validated primarily for stages I-III.5\n\nThe relationship between mutation type and survival rate could not be assessed because no patients had NRAS or BRAF mutations. One patient with KRAS mutation had incomplete follow-up data. Studies have found that the overall survival of patients with KRAS mutations was lower than that of patients with wild-type KRAS (17 vs. 21 months, p = 0.002 in Kaplan-Meier survival analysis).106 Rasmy, Fayed, Omar, and Fahmy also reported consistent result (19.6 vs 25 months, p < 0.001).107\n\nElevated NRAS expression correlates with a risk that is 1.36 times higher for worse overall survival.108 This aligns with the findings presented by Wang et al., where the risk was 1.83 times higher (p < 0.001).109 Similarly, BRAF mutations are associated with a risk that is 1.52 times higher of diminished overall survival compared to BRAF with no mutations (18.9 versus 33.2 months, p < 0.001).110 Notably, patients harboring wild-type KRAS, NRAS, and BRAF mutations exhibited median overall survival durations of 49.2, 36.2, 30.1, and 22.5 months, respectively (p < 0.001).109\n\nThere are some limitations of this study. Several biases may potentially be present in this study and could, at least in part, influence the results. The relatively small sample size, including 74 patients in the current series, reduces statistical power, hence limiting the ability to detect significant associations-between variables like immune score and survival-that may be picked up when analyzing a larger cohort. In such a retrospective cohort, the selection bias may occur because available clinical data relies on clinical information that may not detect all relevant comorbidities of patients. This biases the data into the possible incompleteness of the follow-up data or underreporting of the comorbidities, hence giving biased results. The third is that the loss to follow-up was not accounted for, and the patients who were lost to follow-up were excluded while performing survival analysis, which again may create some bias by undervaluing mortality rates or overestimating survival in a cohort.\n\nThis study extensively investigated the demographic and clinical features of CRC patients, including age, sex, BMI, comorbidities, tumor characteristics, mutation status, immune score, disease stage, metastasis, and treatment. Among the 74 patients treated at Siloam Hospital, the majority were aged 41-70 years, male, and diagnosed with colon cancer. Comorbidities, mainly cardiovascular diseases, affected 36% of patients. Although cancer stage and metastasis were significantly associated with the immune score, no significant relationships were found between the immune score and survival. Although comorbidities were initially linked to survival rates, these associations lost significance after adjusting for confounding variables. Larger studies are warranted to confirm these findings and to elucidate the complex interplay between clinical parameters, immune responses, and survival outcomes in CRC.\n\nThis study was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia. The initial ethical approval number was KET-1096/UN2.F1/ETIK/PPM.00.02/2020, with approval date of September 28th, 2020,, which has been extended to 2025 with the approval number ND-166/UN2.F1/ETIK/PPM.00.02/2024, with approval date of February 28th, 2024. Considering the retrospective nature of this cohort study, the ethical approval committee waived the consent to participate as the research involved the analysis of existing data.",
"appendix": "Data availability\n\nOSF: Demographic profile of colorectal cancer patients in Indonesia: insights from a single-center experience and exploration of immune response and survival outcomes. https://doi.org/10.17605/OSF.IO/M9E85.111\n\nThis project contains the following underlying data:\n\n• Data file 1. MCRC Data_Cosphiadi Irawan_F1000 de-identified.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International Public License.\n\nThis article follows STROBE guidelines for observational studies.\n\nOSF: Demographic profile of colorectal cancer patients in Indonesia: insights from a single-center experience and exploration of immune response and survival outcomes. https://doi.org/10.17605/OSF.IO/M9E85.111\n\nThis project contains the following extended data:\n\n• Data file 1. STROBE Checklist_Cosphiadi Irawan_CRC_F1000.docx\n\n• Data file 2. 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[
{
"id": "356601",
"date": "20 Jan 2025",
"name": "Xishan Wang",
"expertise": [
"Reviewer Expertise Colorectal cancer"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral Overview: The manuscript titled \"The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes\" offers valuable insights into the clinical characteristics, immune responses, and survival outcomes of colorectal cancer (CRC) patients in Indonesia. The study provides an important contribution to the understanding of CRC in a specific geographic region, particularly in terms of tumor biology, immune responses, and comorbidities. Strengths:\nThe study is comprehensive in covering key variables such as tumor characteristics, immune score, comorbidities, and genetic mutations. The manuscript is well-organized, and the methods are clearly outlined, allowing for easy replication of the study. The demographic analysis provides crucial data that can help guide clinical practice and future research, especially in low-resource settings.\nAreas for Improvement:\nStudy Design and Sample Size:\nThe sample size of 74 patients may be too small to draw significant conclusions for some of the subgroups, especially given the retrospective design. Larger, multi-center studies would be beneficial to increase the generalizability of the findings. Consider providing more justification for the study's sample size or discussing its limitations in greater detail.\n\nStatistical Analysis:\nThe manuscript presents multiple p-values related to patient characteristics, immune scores, and survival, but the impact of confounders should be more clearly addressed. Specifically, comorbidities and their effects on survival could be explored in more depth. The study's reliance on unadjusted hazard ratios for survival analysis might not fully account for confounding factors. A more robust multivariate analysis would strengthen the conclusions.\n\nImmune Score and Survival:\nAlthough the study finds a relationship between immune score and survival, the statistical significance is not strong (p = 0.181). It would be helpful to discuss potential reasons for the lack of significance and consider exploring other immunological markers or integrating more advanced immune profiling techniques. Additionally, the absence of immunotherapy in the study population should be noted as a limitation in the interpretation of immune score-related survival data.\n\nComorbidity Impact:\nThe significant effect of cardiovascular comorbidities on survival is an important finding, but further discussion is needed on how these comorbidities interact with cancer treatment regimens and impact patient quality of life. A deeper exploration of the mechanisms by which cardiovascular diseases influence CRC survival would add clarity to this section.\n\nPresentation of Data:\nSome sections of the results could be better summarized, especially in terms of the relationship between patient demographics, tumor characteristics, and immune scores. Tables and figures could be made more concise to enhance readability.\n\nDiscussion and Conclusion:\nThe discussion could benefit from a more thorough comparison with similar studies, particularly those conducted in other parts of Asia or low-resource settings, to highlight regional differences in CRC. Recommendations for future research should be more explicitly stated, especially in regard to exploring the interplay between immune response, tumor mutations, and survival in CRC patients.\n\nMinor Points:\nThere are some typographical and grammatical errors in the manuscript. A thorough proofread is recommended before publication. Consider including a clearer figure legend for the Kaplan-Meier curve presented in Figure 1 to enhance clarity for readers.\nConclusion: Overall, the manuscript provides significant insights into the demographic and clinical characteristics of CRC patients in Indonesia. With some revisions, particularly in the areas of statistical analysis, sample size justification, and the discussion of immune scores, this manuscript has the potential to make a valuable contribution to the literature.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1362
|
https://f1000research.com/articles/13-1361/v1
|
13 Nov 24
|
{
"type": "Research Article",
"title": "Analysis of Circulating Plasma MicroRNA Profile in Low-Grade and High-Grade Glioma – A Cross-Sectional Study",
"authors": [
"Ery Kus Dwianingsih",
"Rachmat Andi Hartanto",
"Sekar Safitri",
"Yeshua Putra Krisnugraha",
"Christina Megawimanti Sianipar",
"Endro Basuki",
"Kusumo Dananjoyo",
"Ahmad Asmedi",
"Bo Sun",
"Rusdy Ghazali Malueka",
"Ery Kus Dwianingsih",
"Rachmat Andi Hartanto",
"Sekar Safitri",
"Yeshua Putra Krisnugraha",
"Christina Megawimanti Sianipar",
"Endro Basuki",
"Kusumo Dananjoyo",
"Ahmad Asmedi",
"Bo Sun"
],
"abstract": "Background Glioma is the second most common type of brain tumor, accounting for 24% of all brain tumor cases. The current diagnostic procedure is through an invasive tissue sampling to obtain histopathological analysis, however, not all patients are able to undergo a high-risk procedure. Circulating microRNAs (miRNAs) are considered as promising biomarkers for glioma due to their sensitivity, specificity, and non-invasive properties. There is currently no defined miRNA profile that contributes to determining the grade of glioma. This study aims to find the answer for “Is there any significant miRNA that able to distinguish different grades of glioma?”.\n\nMethods This study was conducted to compare the expression of miRNAs between low-grade glioma (LGG) and high-grade glioma (HGG). Eighteen blood plasma samples from glioma patients and 6 healthy controls were analyzed for 798 human miRNA profiles using NanoString nCounter Human v3 miRNA Expression Assay. The differential expressions of miRNAs were then analyzed to identify the differences in miRNA expression between LGG and HGG.\n\nResults Analyses showed significant expressions in 12 miRNAs between LGG and HGG, where all of them were downregulated. Out of these significant miRNAs, miR-518b, miR-1271-3p, and miR-598-3p showed the highest potential for distinguishing HGG from LGG, with area under curve (AUC) values of 0.912, 0.889, and 0.991, respectively.\n\nConclusion miR-518b, miR-1271-3p, and miR-598-3p demonstrate significant potentials in distinguishing LGG and HGG.",
"keywords": [
"Glioma",
"grade",
"circulating miRNA",
"blood plasma",
"NanoString",
"biomarker"
],
"content": "Introduction\n\nGlioma is the second most common type of brain tumor, accounting for 24% of all brain tumor cases, with meningioma being the most common.1 Glioma is a broad term that encompasses many different subtypes, but it is typically divided into two main categories: low-grade glioma (LGG) and high-grade glioma (HGG), which are classified by the World Health Organization (WHO) as Grade 1-2 and Grade 3-4, respectively. Glioblastoma (GBM) is one of the most aggressive and malignant forms of high-grade glioma. Despite significant advances in diagnostic and treatment technologies, the mortality rate for glioblastoma remains high, with an average life expectancy of only 1.5 years.2 Currently, most cases of glioma are detected using magnetic resonance imaging (MRI), followed by surgery to obtain a tissue sample for histopathological analysis to determine the subtype and grade of the tumor. However, there is a significant problem with inter-observer variability in both radiological and histopathological analysis, which can lead to diagnostic errors.3 In addition, sampling errors can occur if the tumor is not biopsied adequately.4 This invasive diagnostic procedure poses many risks to patients, and not all patients are able to undergo it.\n\nMicroRNA (miRNA) is a small endogenous mediator for RNA interference and a crucial regulatory component for biological development and metabolism.5,6 It is a group of 18-25 nucleotides that exhibits distinct expression patterns in various types of cancer tissue.7,8 Many miRNAs demonstrate tissue-specific expression patterns and can exhibit either oncogenic or suppressive properties depending on the processes.9 Moreover, miRNA can cross the blood-brain barrier and exist stably in peripheral circulation. Therefore, miRNA is a strong candidate for a circulatory biomarker for brain tumors, specifically glioma.10 Multiple studies have demonstrated the use of single miRNA or a combination of multiple miRNAs for diagnostic and prognostic purposes in GBM.11 For instance, a study by Yang et al. identified significant differences in seven miRNAs between high-grade astrocytoma and normal control.12 Another study by Roth et al. showed the upregulation of miR-128 and downregulation of miR-342-3p in GBM patients.13\n\nPlasma miRNA is a promising diagnostic tool that is less invasive and has more specific targets. The current WHO approach to glioma diagnosis extensively involves molecular profiling. However, there is inadequate evidence for miRNA profiling in Indonesia, which highlights the need to increase knowledge and awareness of miRNA profiling as a promising modality for glioma diagnosis. This study aims to analyze the existing miRNAs and compare them between LGG and HGG and find the answer for “Is there any significant miRNA that able to distinguish different grades of glioma?”. The results may determine any significant miRNA that are uniquely expressed in either HGG or LGG, which can help in accurate diagnosis of glioma.\n\n\nMethods\n\nWritten informed consent was obtained from the patients or from the patients’ families if the patients were deemed incapable of giving consent (decreased consciousness, severe cognitive impairment). The entire study was approved on 26 May 2023 and supervised by the Medical and Health Research Ethics Committee (MHREC), Universitas Gadjah Mada (UGM), Indonesia (Ref: KE/FK/0878/EC/2023). All ethical considerations were conducted and supervised with a strict relevant guideline and regulation.\n\nThis study retrospectively collected data on newly-diagnosed cases of glioma (n = 18) from Dr. Sardjito General Hospital and its satellite hospitals in Yogyakarta, Indonesia. The data was collected over a period of three years (July 2019-July 2022). Additionally, control samples of healthy people (n = 6) were acquired during this data collection. The cases were divided into two groups based on the 2016 WHO Classification of CNS Tumors, which is LGG and HGG. The diagnosis of glioma, including its histopathology, was confirmed by expert neuropathologists from the Department of Anatomical Pathology at Dr. Sardjito General Hospital. Each patient received personalized standardized therapy based on their diagnosis and clinical condition. Basic demographic, clinical, and supportive examinations, such as pathology and radiology, were obtained from medical records. Preoperative blood samples were taken during tumor resection procedures. The entire study protocol was approved by the Medical and Health Research Ethics Committee (MHREC), Universitas Gadjah Mada (UGM), Indonesia (Ref: KE/FK/0878/EC/2023).\n\nBlood samples were taken from a peripheral vein or artery using ethylenediamine-tetra acetic acid (EDTA) anticoagulated tubes. To ensure anonymity, all samples were coded according to the ethics protocol. The sample was immediately centrifuged at 3000×g for 10 minutes, and the plasma was separated and stored at -80°C for further analysis. Additionally, the Buffy coat was also extracted and kept for future study purposes.\n\nThe plasma samples were thawed at room temperature. Afterwards, total cell-free RNA was extracted from plasma and purified by using miRNeasy Serum/Plasma Advanced Kit (Cat. no. 217204) (Qiagen, Germany). For every 200 μl of plasma sample, 60 μl of buffer RPL containing guanidine thiocyanate and detergents was mixed thoroughly and kept in room temperature for 2-3 minutes before adding 20 μl of buffer RPP. Another vigorous mixing and 3-minute room temperature incubation (15-25°C) were performed. The sample was centrifuged at 12000 g for 3 minutes and should produce a clear and colorless supernatant. 1 volume of isopropanol was added to the supernatant and centrifuged at ≥8000 g for 15 seconds followed by addition of 700 μl of buffer RWT and centrifugation at ≥8000 g for 15 seconds. Next, 500 μl of buffer RPE was mixed and centrifuged again at ≥8000 g for another 15 seconds. Lastly, the mixture was mixed with 50 μl of 80% ethanol before centrifugation at ≥8000 g for 2 minutes. The sample was then washed with 20 μl of RNAse-free water and incubated for 1 minute before 1-minute full speed centrifugation to completely elute the RNA. The final mixture was ready to be used for further analysis. Each step was performed according to the standard protocol issued by the manufacturer. To assess the quality of the RNA, a Nanodrop device (Thermo Scientific, Waltham, MA, USA) was used.\n\nA NanoString nCounter Human v3 miRNA Expression Assay (Cat. no. CSO-MIR3-12) (NanoString Technologies, Seattle, WA, USA) was conducted on all samples. The assay used 798 unique miRNA barcodes. To perform the analysis, 100 ng total cell-free RNA from each sample was mixed with pairs of capture and reporter probes customized for specific recognition of each miRNA presence. Overnight hybridization at a temperature of 65°C allowed sequence-specific probes to form complexes with targets. Two-step magnetic-beads-based purification on an automated fluidic handling system (nCounter Prep Station, Thermo Scientific, Waltham, MA, USA) was used to remove excess probes, and target-probe complexes were immobilized on the cartridge for data collection. Data collection was carried out on the nCounter Digital Analyzer (NanoString Technologies, Seattle, WA, USA) following the manufacturer’s instructions, to count individual fluorescent barcodes and quantify target RNA molecules present in each sample. For each assay, a high-density scan (600 fields of view) was performed.\n\nThe NanoString raw data or Reporter Code Counts (RCC) file was analyzed using nCounter analysis software developed by ROSALIND, Inc (ROSALIND, San Diego, CA) (https://rosalind.bio/) which employs a HyperScale architecture for bioinformatics problem solving. As part of the quality control step, ROSALIND generated Read Distribution percentages, violin plots, identity heatmaps, and sample MDS plots. Nanostring’s criteria were used to calculate normalization, fold changes, and p-value s. Background subtraction was performed based on POS_A probe correction factors, followed by normalization in two steps: positive control normalization and codeset normalization. During both normalization steps, the geometric mean of each probeset was used to create a normalization factor. ROSALIND employed the t-test method to calculate fold changes and p-values for comparisons. p-value adjustment was performed using the Benjamini-Hochberg method to estimate false discovery rates (FDR). For the final heatmap of differentially expressed miRNA, clustering was done using the PAM (Partitioning Around Medoids) method with the fpc R library. This method takes into consideration the direction and type of all signals on a pathway, as well as the position, role, and type of every miRNA. As an alternative software, an open-source bioinformatics tool is provided by Illumina in GitHub and is available to use (https://github.com/Illumina).\n\nRelevant data were extracted from ROSALIND and statistical analysis was performed using IBM SPSS Ver. 26 using glioma grading and miRNA reposited dataset14 to generate demographic data and analysed the correlation between LGG and HGG with candidate miRNA. The first step was to generate boxplots for all unique significantly expressed miRNAs based on ROSALIND analysis. p-value was determined using Kruskal Wallis Test. ROC-AUC graph were then generated using the normalized expression of candidate miRNA. All significant miRNAs were subjected to univariate analysis using Mann-Whitney Test to determine their correlation with glioma grading. A p-value of less than 0.05 was considered significant in all tests.\n\n\nResults\n\nIn this study, a total of 24 subjects were enrolled. Out of these, 6 individuals (25%) were healthy controls, while 6 (25%) were diagnosed with diffuse astrocytoma, 6 (25%) with anaplastic astrocytoma, and another 6 (25%) with GBM ( Table 1). This means that among the tumor group, 6 (33.3%) were classified as LGG, and 12 (66.6%) as HGG. Among the subjects with tumors, 11 (61.1%) were male and 7 (38.9%) were female. Most of them (15 samples) were under the age of 60, while the remaining 3 (16.7%) were over 60. The tumors were mostly located in the frontal lobe, while some involved parietal and/or temporal lobes. Twelve (66.7%) of the tumors had a wildtype IDH1, while the other 6 (33.3%) had a mutant IDH1.\n\nA total of 21 miRNAs were significantly observed in the samples, out of which 5 were upregulated, and 16 were downregulated ( Table 2). MiR-223-3p exhibited the highest fold changes as compared to other upregulated miRNAs. However, the adjusted p-value did not show significance (p=0.088). On the other hand, miR-1271-3p exhibited the biggest fold change with a value of -2.249 compared to other downregulated miRNAs, with an adjusted p-value of 0.010.\n\n* p-value calculated by ROSALIND®, <0.05 is considered statistically significant.\n\nThese significantly expressed miRNAs were further analyzed to determine their ability to distinguish between HGG and LGG. These 12 miRNAs will be further represented as box plots in Figures 1A-1L to provide a visual representation of their significance.\n\n♦: extreme outlier; ο: mild outlier; CTRL: control; LGG: low-grade glioma; HGG: high-grade glioma.\n\nMost miRNAs were highly expressed in LGG compared to HGG and control groups, with all showing a significant p-value of less than 0.05 as depicted in Figure 1. Table 3 displays the AUC results for the miRNAs analyzed. According to the results, miR-518b, miR-1271-3p, and miR-598-3p showed AUC values of 0.912, 0.889, and 0.991, respectively. These miRNAs have a high true positive rate for distinguishing between LGG and HGG. The ROC Curve will be individually displayed for miR-518b ( Figure 2A), miR-1271-3p ( Figure 2B), and miR-598-3p ( Figure 2C). On the other hand, the AUC values for miR-216a-5p, miR-6721-5p, miR-23c, miR-4443, miR-363-3p, miR-873-3p, miR-127-5p, miR-1286, and miR-550a-5p were low.\n\n* AUC: Area Under Curve.\n\nα p-value <0.05.\n\n** Mann-Whitney Test.\n\nThe positive actual state is high-grade glioma (HGG); p-value <0.05 is considered statistically significant.\n\nAUC: Area Under Curve; CI: Confidence Interval.\n\nUnivariate analysis was conducted using the Mann-Whitney test to compare the expression of miRNAs between HGG and LGG. The results indicated that miR-518b, miR-1271-3p, miR-4443, miR-873-3p, miR-127-5p, miR-1286, and miR-550a-5p have significantly lower expression in HGG compared to LGG (with a p-value of less than 0.05).\n\n\nDiscussion\n\nThis study has identified several circulating plasma miRNAs that exhibit significantly lower expression in HGG as compared to LGG. Notably, miR-518b, miR-1271-3p, and miR-598-3p demonstrated high AUC values. There is still limited data available on circulating miRNA profiling in glioma. Dysregulation of miRNA has been observed to contribute to various aspects of gliomagenesis, including regulation of cancer stem cells, cell cycle control, apoptosis, angiogenesis, and immune modulation.15\n\nMiR-518b is a type of miRNA that has been found to be significantly expressed in patients with hepatocellular carcinoma (HCC). It has also been associated with the prognosis of HCC patients. However, there is no study linking this miRNA with glioma patients.16 A box plot, shown in Figure 1A, displays a noticeable increase in its expression in LGG patients when compared to HGG patients. Additionally, it shows a 91.2% AUC in ROC Curve, as visualized in Figure 2A, which means that this miRNA has a high capability in distinguishing between LGG and HGG based on its expression level. A previous study found that miR-518a-3p downregulation has a role in decreasing NF-kB inducing kinase (NIK) protein levels in patients with colorectal cancer. This, in turn, lowers NF-kB activity and increases resistance to apoptosis.17 In glioma patients, NF-kB is activated more in HGG.18 NF-kB has a role in mediating inflammatory cytokines regulation, and a study has found an increased miR-518 expression in human endothelial cells that have been exposed to oxidative stress and inflammation. These findings were done in patients with ischemic cerebral infarction.19 Therefore, a higher expression of miR-518b in LGG may associate with a higher NF-kB suppression through NIK downregulation, resulting in a lower grade of glioma.\n\nMiR-1271-3p has been studied and found to have a direct pathway in regulating calcium/calmodulin-dependent protein kinase 2 (CaMKK2).20 It also contributes, together with zinc finger antisense 1 (ZFAS1) and hexokinase 2 (HK2), in regulating growth in glioma tissues.21 Both studies showed that lower expression of CaMKK2 and ZFAS1 were associated with upregulation in miR-1271-3p while interacting with HK2, therefore constraining proliferation, migration, and apoptosis of tumor cells. This is consistent with a significantly higher miR-1271-3p expression in LGG compared to HGG, including GBM, as shown in Figure 1B. Several studies involving various cancers also showed a significant association between miR-1271 overexpression and cell growth inhibition, as seen in oral squamous cell carcinoma (OSCC) and ovarian cancer.22,23 Both studies implicate that lower expression of miR-1271 will promote cancer cell growth and even metastatic possibility.\n\nThere have been limited studies on the activity of hsa-miR-598-3p in tumor regulation. However, one study found a connection between miR-598 and the Metastasis Associated Colon Cancer (MACC1) gene through direct inhibition. MACC1 is highly expressed in GBM, and miR-598 was found to have a direct impact on inhibition of proliferation and invasion through MACC1.24 This suggests that in HGG patients, including GBM, lower levels of miR-598 will be detected compared to LGG due to its natural inhibitive nature. This study supports previous findings as seen in Figure 1C. While not many studies have focused on miR-598 and glioma patients, numerous other studies have revealed that miR-598 has a natural property of inhibiting cell growth and proliferation. Downregulated miR-598 has also been linked to inhibition of gastric cancer cells proliferation, migration, and apoptosis in cases of gastric cancer (GC), osteosarcoma, non-small cell lung carcinoma (NSCLC), and colorectal cancer metastasis.25–27 Consequently, cancer patients with lower expression of miR-598 will most likely have higher severity or grading compared to low-grade cancer patients, including glioma. Despite significant findings, this study is limited to a small sample size, therefore, another study with larger sample size and more controlled variables needs to be conducted in order to achieve a more conclusive result.\n\n\nConclusion\n\nIn conclusion, this study has demonstrated that miR-518b, miR-1271-3p, and miR-598-3p are plasma miRNAs that possess the ability to differentiate between low-grade and high-grade glioma. These miRNAs are overexpressed in low grade gliomas, which is consistent with their role as tumor suppressors. However, this study’s limitation lies in its small sample size, which highlights the need for further validation in a larger group of glioma patients.\n\n\nDeclarations\n\nWritten informed consent was obtained from the patients or from the patients’ families if the patients were deemed incapable of giving consent (decreased consciousness, severe cognitive impairment). The entire study was approved on 26 May 2023 and supervised by the Medical and Health Research Ethics Committee (MHREC), Universitas Gadjah Mada (UGM), Indonesia (Ref: KE/FK/0878/EC/2023).\n\nWritten informed consent was obtained from the patients or from the patients’ families if the patients were deemed incapable of giving consent (decreased consciousness, severe cognitive impairment), including the liberty to use patients’ demographic and clinical information for publication without disclosing patients’ identities. Consent to publish was communicated to the patients or the patients’ families together with consent to participate in the study.\n\nThis study did not preregister any data analysis plan at an independent registry.\n\n\nSoftware availability\n\nROSALIND and IBM SPSS Ver. 26 were used for nCounter analysis and statistical analysis, respectively. ROSALIND is a subscription-based tool developed by ROSALIND, Inc (https://rosalind.bio/). Alternatively, GitHub by Illumina provides various open-source bioinformatics tools which is available for use (https://github.com/illumina).",
"appendix": "Data availability\n\nHarvard Dataverse: Integrated Datalog MicroRNA and Glioma Grade https://doi.org/10.7910/DVN/N3WTWV.28\n\nThe dataset contains following underlying data:\n\n• Full Data Nanostring (290423).tab (Include subject ID, baseline characteristics, glioma subtype and location, and normalized MiRNA expressions)\n\n• MiRNA Glioma Grade 2 Only.tab (control sample vs glioma subjects grade 2 normalized MiRNA expressions)\n\n• MiRNA Glioma Grade 3 Only.tab (control sample vs glioma subjects grade 3 normalized MiRNA expressions)\n\n• MiRNA Glioma Grade 4 Only.tab (control sample vs glioma subjects grade 4 normalized MiRNA expressions)\n\nData are available under the terms of Creative Commons CC0 1.0 Universal Public Domain Dedication.\n\n\nAcknowledgement\n\nNot applicable.\n\n\nReferences\n\nOstrom QT, Gittleman H, Truitt G, et al.: CBTRUS statistical report: Primary Brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro-Oncology. 2018; 20(suppl_4): iv1–iv86. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan Meir EG, Hadjipanayis CG, Norden AD, et al.: Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J. Clin. 2010; 60(3): 166–193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeyer S, Fleming J, Meng W, et al.: The role of mirnas in angiogenesis, invasion and metabolism and their therapeutic implications in gliomas. Cancers. 2017; 9(7): 85. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDrusco A, Bottoni A, Laganà A, et al.: A differentially expressed set of micrornas in cerebro-spinal fluid (CSF) can diagnose CNS malignancies. Oncotarget. 2015; 6(25): 20829–20839. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTomaru Y, Hayashizaki Y: Cancer research with non-coding RNA. Cancer Sci. 2006; 97(12): 1285–1290. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChan JA, Krichevsky AM, Kosik KS: Data from MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.2023. Publisher Full Text\n\nGourlay J, Morokoff AP, Luwor RB, et al.: The emergent role of exosomes in glioma. J. Clin. Neurosci. 2017; 35: 13–23. Publisher Full Text\n\nMitchell PS, Parkin RK, Kroh EM, et al.: Circulating micrornas as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. 2008; 105(30): 10513–10518. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSvoronos AA, Engelman DM, Slack FJ: Oncomir or tumor suppressor? the duplicity of micrornas in cancer. Cancer Res. 2016; 76(13): 3666–3670. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorokoff A, Jones J, Nguyen H, et al.: Serum microrna is a biomarker for post-operative monitoring in Glioma. J. Neuro-Oncol. 2020; 149(3): 391–400. PubMed Abstract | Publisher Full Text\n\nGéczi D, Nagy B, Szilágyi M, et al.: Analysis of circulating MIRNA profile in plasma samples of glioblastoma patients. Int. J. Mol. Sci. 2021; 22(10): 5058. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang C, Wang C, Chen X, et al.: Identification of seven serum micrornas from a genome-wide serum microrna expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int. J. Cancer. 2012; 132(1): 116–127. PubMed Abstract | Publisher Full Text\n\nRoth P, Wischhusen J, Happold C, et al.: A specific MIRNA signature in the peripheral blood of glioblastoma patients. J. Neurochem. 2011; 118(3): 449–457. PubMed Abstract | Publisher Full Text\n\nMalueka RG: Integrated Datalog MicroRNA and Glioma Grade.[Dataset]. Harvard Dataverse. 2024; V1. Publisher Full Text\n\nZhao H, Shen J, Hodges TR, et al.: Serum microrna profiling in patients with glioblastoma: A survival analysis. Mol. Cancer. 2017; 16(1): 59. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYerukala Sathipati S, Ho S-Y: Novel mirna signature for predicting the stage of hepatocellular carcinoma. Sci. Rep. 2020; 10(1): 14452. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaubach G, Feige MH, Lim MCC, et al.: NF-Kappab-inducing kinase in cancer. Biochimica et Biophysica Acta (BBA) - Reviews on. Cancer. 2019; 1871(1): 40–49. Publisher Full Text\n\nPuliyappadamba VT, Hatanpaa KJ, Chakraborty S, et al.: The role of NF-κB in the pathogenesis of Glioma. Mol. Cell. Oncol. 2014; 1(3): e963478. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao B, Jiang X: HSA-mir-518-5p/HSA-mir-3135b regulates the REL/sod2 pathway in ischemic cerebral infarction. Front. Neurol. 2022; 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang Y-K, Su Y-F, Lieu A-S, et al.: Mir-1271 regulates glioblastoma cell proliferation and invasion by directly targeting the CAMKK2 gene. Neurosci. Lett. 2020; 737: 135289. PubMed Abstract | Publisher Full Text\n\nZhang B, Chen J, Cui M, et al.: LncRNA ZFAS1/mir-1271-5p/HK2 promotes glioma development through regulating proliferation, migration, invasion and apoptosis. Neurochem. Res. 2020; 45(12): 2828–2839. PubMed Abstract | Publisher Full Text\n\nHuang S, Huang P, Wu H, et al.: Linc02381 aggravates breast cancer through the mir-1271-5p/FN1 axis to activate PI3K/akt pathway. Mol. Carcinog. 2021; 61(3): 346–358. PubMed Abstract | Publisher Full Text\n\nLiu X, Ma L, Rao Q, et al.: Mir-1271 inhibits ovarian cancer growth by targeting cyclin G1. Med. Sci. Monit. 2015; 21: 3152–3158. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang N, Zhang Y, Liang H: MicroRNA-598 inhibits cell proliferation and invasion of glioblastoma by directly targeting metastasis associated in colon cancer-1 (MACC1). Oncol. Res. 2018; 26(8): 1275–1283. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu N, Yang H, Wang H: Mir-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R. Onco. Targets. Ther. 2018; 11: 2911–2923. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang F, Wei K, Qin Z, et al.: Mir-598 suppresses invasion and migration by negative regulation of derlin-1 and epithelial-mesenchymal transition in non-small cell lung cancer. Cell. Physiol. Biochem. 2018; 47(1): 245–256. PubMed Abstract | Publisher Full Text\n\nChen J, Zhang H, Chen Y, et al.: Mir-598 inhibits metastasis in colorectal cancer by suppressing Jag1/NOTCH2 pathway stimulating EMT. Exp. Cell Res. 2017; 352(1): 104–112. PubMed Abstract | Publisher Full Text\n\nMalueka RG: Integrated Datalog MicroRNA and Glioma Grade. [Dataset]. Harvard Dataverse. 2024; V1. Publisher Full Text"
}
|
[
{
"id": "348009",
"date": "31 Dec 2024",
"name": "Emiliya Nikolova",
"expertise": [
"Reviewer Expertise Neuro-oncology",
"miRNA analysis",
"biomarker analysis"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. Is the work clearly and accurately presented and does it cite the current literature?\nI recommend updating the introduction with the latest research - some references cited are outdated. The authors use the 2021 WHO grading in the introduction but refer to the previous WHO classification in later sections. It is recommended to consistently use the latest 2021 WHO CNS classification throughout the paper.\n\n2. Is the study design appropriate and is the work technically sound?\nI would like to ask for additional information regarding the clarification of the ethical approval before sample collection and sample quality control (the authors have used blood samples for the RNA analysis that have been stored for more than three years).\n\n3 . Are sufficient details of methods and analysis provided to allow replication by others?\nWhat is the data distribution and how do the authors determine it? Authors used combination of parametric and non-parametric tests in a small sample size, so conclusions drawn from it should be made with caution.\n4. If applicable, is the statistical analysis and its interpretation appropriate? I also have some few statistical concerns regarding the data analysis: the 3 groups (6 LGG, 12 HGG and 6 controls) are too small as a sample size and the used statistical tests require a larger cohort to ensure the reliability and validity of results. The risk of Type I and Type II errors are high\n5. Are the conclusions drawn adequately supported by the results? The study may not be correctly analyzed statistically. I recommend to increase the sample size or to perform an independent validation study of the selected miRs\nAdditional questions and recommendations: - You should provide inclusion and exclusion criteria - Are there any data for the OS and PFS of patients with HGG? Characteristics such as tumour location, IDH, OS, PFS should be also include in the patients' table. - Authors stated that “ However, there is no study linking this miRNA (miR-518b) with glioma patients.16” but indeed there are several studies on this. The discussion should be widening including more studies on using miRs for differentiation HGG and LGG as well as discussing the role of the selected miR in brain malignancies. - What is the explanation of higher expression of the selected miRs in the LGG compared to controls and HGG?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "353046",
"date": "08 Jan 2025",
"name": "Hope Richard",
"expertise": [
"Reviewer Expertise surgical neuropathology",
"cancer genetics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article describes a non-invasive protocol for the diagnosis of glioma through circulating miRNAs. A small group of patients were enrolled to establish if the grade of glioma could be inferred by the circulating miRNA pattern with the conclusion that miR-518b, miR-1271-3p, and miR-598-3p showed some differential expression when comparing low grade and high-grade gliomas. The weaknesses of the study center predominately around the size of the study population. It would also be useful to re-classify the lesions histologically/molecularly using the 5th edition tumor classification criteria.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "353043",
"date": "10 Jan 2025",
"name": "Karla F Meza-Sosa",
"expertise": [
"Reviewer Expertise non-coding RNAs",
"microRNAs",
"long non-coding RNAs",
"lncRNAs",
"post-transcriptional regulation of gene expression",
"cancer"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this article, the authors collected plasma samples from healthy controls and 18 people diagnosticated with either low-grade or high-grade glioma and measured the expression of 798 microRNAs. Even though the sample size is small, interesting results were obtained as 3 plasma miRNAs (miR-518b, miR-1271-3p, and miR-598-3p) apparently have the potential to distinguish between low- and high-grade gliomas. However, the performed statistical tests throughout the manuscript are not clearly defined and explained accordingly to the type of analyzed data. Please talk about data distribution for each experiment and then, using that information justify the used statistical tests.\nAlso, more discussion regarding possible molecular mechanisms regulated by the found miRNAs and making hypothesis about them is needed. The article is very interesting and promising to consolidate plasma microRNAs levels as a valuable diagnostic, prognostic and/or classification tool for gliomas in this specific population (Indonesian). However, as mentioned in the conclusion of the paper, data should be taken carefully due to sample size.\nMajor comments:\nIt is not very clear if Figure 1 data are based on the NanoString nCounter Expression Assay or if these miRNAs´ expression was validated by performing qPCR after. Please specify it and, if qPCR was not performed, it would be necessary to validate the obtained results at least for miR-518b, miR-1271-3p, and miR-598-3p.\nMinor comments:\nPlease check and correct grammar and spelling throughout all your manuscript. Please write microRNAs instead of microRNA when corresponding throughout all your manuscript and change verbs to plural conjugation accordingly.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "353045",
"date": "11 Jan 2025",
"name": "Nirenjen Shanmugasundaram",
"expertise": [
"Reviewer Expertise Endocrine disorders",
"wound healing",
"Diabetes",
"Nanofibres"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript titled \"Analysis of Circulating Plasma MicroRNA Profile in Low-Grade and High-Grade Glioma – A Cross-Sectional Study\" presents a valuable contribution to glioma research by exploring a non-invasive diagnostic approach using circulating plasma miRNAs. The identification of miR-518b, miR-1271-3p, and miR-598-3p as potential biomarkers offers a promising alternative to invasive diagnostic techniques, addressing a critical need in neuro-oncology. The study’s methodology is well-detailed, and the results are statistically significant, showcasing the potential of these miRNAs in differentiating glioma grades. This research is particularly important given the challenges of early and accurate glioma diagnosis and the limitations of current diagnostic procedures.\nHowever, there are a few clarifications and improvements that could enhance the study's rigor and reliability.\nThe sample size of 18 glioma patients and 6 controls is limited, which affects the robustness of the results. Expanding the cohort or conducting a validation study would strengthen the findings and improve reliability.\nAdditionally, there is inconsistency in the use of the 2021 WHO CNS tumor classification, which should be uniformly applied throughout the manuscript for clarity.\nSome references are outdated, and recent studies on miR-518b and its role in gliomas should be incorporated to provide a more comprehensive discussion.\nThe statistical analysis raises concerns due to the small sample size, which may increase the risk of Type I and Type II errors.\nThe rationale for using parametric and non-parametric tests should be explained more thoroughly, and additional validation techniques, such as bootstrapping, could be considered.\nMoreover, the manuscript lacks key clinical variables, such as Overall Survival (OS), Progression-Free Survival (PFS), and tumor location. Including these variables in the patient data and correlating them with miRNA expression would significantly enhance the study's clinical relevance.\nThe discussion section does not adequately explain why the selected miRNAs are upregulated in low-grade gliomas compared to high-grade gliomas. Providing mechanistic insights or hypotheses linking these findings to glioma biology would improve the study’s impact. Furthermore, the quality control measures for RNA samples stored for over three years need elaboration to ensure data integrity. The inclusion and exclusion criteria for patient selection should also be clearly outlined. Lastly, the study's limitations, such as the small sample size and single-center nature, should be explicitly acknowledged.\nAddressing these clarifications will significantly improve the manuscript's quality and its potential impact on glioma research and clinical diagnostics.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1361
|
https://f1000research.com/articles/13-1360/v1
|
13 Nov 24
|
{
"type": "Opinion Article",
"title": "Climate Change and Veterinary Medicine: A Call to Action for a Healthier Planet",
"authors": [
"Winnifred Akello"
],
"abstract": "Abstract Climate change is rapidly transforming ecosystems and reshaping the landscapes of animal health, with profound consequences for public health, food security, and biodiversity. Rising temperatures, shifting weather patterns, and increased frequency of natural disasters are driving the emergence and spread of infectious diseases, particularly zoonotic and vector-borne diseases. These environmental shifts endanger the health and welfare of animals and the delicate balance between human populations, livestock, and wildlife. As the stewards of animal health, veterinarians are uniquely positioned to lead the change in addressing these complex challenges at the nexus of human, animal, and environmental health and well-being. This article calls for urgent actions to integrate climate adaptation and mitigation strategies into veterinary practice and education. It underscores the critical need for veterinarians to embrace the One Health approach to tackle climate-driven disease outbreaks and the growing threat of antimicrobial resistance to safeguard human and animal populations while protecting natural ecosystems. The article further explores the role of veterinarians in fostering sustainable agricultural practices, reducing the environmental impact of livestock production, conserving biodiversity and advocating for policy reforms that protect both animal and planetary health. As we face an era of unprecedented climate disruption, this call to action aims to inspire the global veterinary community to actively get involved in combating climate change and its worst impacts. By building climate-resilient practices, enhancing disease surveillance, and championing environmental stewardship, veterinarians can contribute significantly to a healthier, more sustainable future for all species on Earth.",
"keywords": [
"Climate Change",
"Veterinarians",
"One Health",
"Climate-Resilience",
"Sustainable Agriculture",
"Biodiversity",
"Public Health",
"Climate Action"
],
"content": "Introduction\n\nIn the face of one of the most pressing challenges of our time – climate change – the veterinary profession stands at a critical juncture. Often perceived solely as protectors of animal health, veterinarians now find themselves as frontline defenders of the environment, public health, and the fragile ecosystems that sustain all life. Climate change is not just an environmental issue; it is a public health emergency that deeply affects human, animal, and ecological well-being. It is time for the veterinary community to rise to the challenge, embrace a proactive role in combating climate change, and lead with the values of the One Health approach.\n\nThe connection between climate change and animal health is multi-dimensional. Animals, specifically livestock, are a significant factor in the greenhouse gas emissions associated with agriculture, contributing approximately 14.5% of all anthropogenic greenhouse gases globally (FAO 2017). At the same time, climate change is threatening all life. Increasing temperatures, rising sea levels, frequent extreme weather events like floods, cyclones, droughts, and uncontrollable wildfires (Dey and Lewis 2021) are the harrowing realities of a rapidly changing climate. These changes disrupt ecosystems, destroy habitats, shift disease patterns and drive unprecedented biodiversity loss (Upadhyay 2020).\n\nVeterinarians are already seeing the consequences: vector-borne diseases such as bluetongue virus and parasitic infections in livestock are spreading and becoming more prevalent in once-safe areas (Lacetera 2019). Heat stress in livestock reduces productivity and increases disease vulnerability (FAO 2020). Wild animals are migrating in search of cooler habitats, and many have become extinct (Ziswiler 2012), while pets face new health challenges as their environments change (Narayan 2023).\n\nAs stewards of animal health, veterinarians cannot watch as the climate crisis endangers the very species we have sworn to protect.\n\nAt the heart of veterinary medicine is the One Health principle, which emphasizes that human, animal, and environmental health are inextricably linked. Climate change is driving home this truth with brutal clarity. The rise in zoonotic diseases like avian influenza, Dengue and Rift Valley fever, the increased threat of food insecurity, and foodborne pathogens are direct consequences of climate-driven environmental disruptions (Rupasinghe et al. 2022). Additionally, climate change has been linked to antimicrobial resistance because of the alarming spread of diseases, which results in the escalating use of antimicrobials (Lio et al. 2023).\n\n\nWhy must the veterinary professionals act?\n\nSafeguarding animal health is safeguarding human health. The veterinary profession must become advocates for environmental stewardship, educators in sustainable practices, and innovators in mitigating the impacts of climate change on health. Here is why and how the veterinary professionals must act:\n\nZoonotic disease prevention: As climate change alters disease patterns and drives wildlife closer to domestic animals and human populations, veterinarians play a crucial role in early disease detection and response to outbreaks. By preventing zoonotic diseases, we are preventing future pandemics.\n\nSustainable agriculture: The veterinary profession can champion sustainable, climate-smart livestock practices. Advising farmers on sustainable livestock management can reduce greenhouse gas emissions, mitigate deforestation, and support food security.\n\nBiodiversity conservation: Veterinarians have the knowledge and tools to protect endangered species and promote biodiversity. With climate change contributing to habitat destruction, veterinarians must work closely with conservationists to safeguard wildlife and preserve ecosystems.\n\nClimate-resilient practices: Veterinarians can encourage climate resilience within the industry by promoting better practices for animal care in extreme weather conditions, such as heat stress management, disease prevention, and water conservation. These help build sustainable, adaptive systems that protect both livelihoods and ecosystems.\n\nCommunity leadership: Veterinarians are trusted voices in their communities. We can lead awareness campaigns, educate the public on the effects of climate change on animal health that would significantly impact human health, and advocate for policies that promote climate actions at local, national, and international levels.\n\n\nThe time to act is now\n\nThere is no more time for complacency. The worst impacts of climate change are already here, and we must harness the power of veterinary medicine as a tool for climate action and health security. The veterinary profession must be more than reactive; it must be proactive.\n\nAs climate advocates, veterinarians can push for systemic changes that support sustainable livestock farming, wildlife conservation, responsible use of natural resources and more robust environmental protection. Moreover, we can lobby for more significant investments in climate resilience research, primarily disease surveillance and prevention.\n\nThe urgency is apparent. Each of us has a role to play. It is time to rethink how we educate future veterinarians. Veterinary schools must adapt their curriculum to address climate change. Veterinary practices must work towards reducing their carbon footprints and modelling sustainability. Furthermore, veterinary voices must join the growing chorus demanding climate justice for all species.\n\n\nConclusions\n\nIn conclusion, veterinarians have the expertise, the influence, and the moral responsibility to act. As climate change alters our world, veterinarians must become the champions of a vision where animals, humans, and the environment can thrive together. Every veterinarian, veterinary student, and allied professional must become a climate warrior, advocating for sustainable livestock practices, speaking up for animal welfare, pushing for climate-focused education in institutions, joining climate initiatives and lobbying for policy changes that protect the planet. The challenges may seem impossible, but every action counts. Together, we can shape a future where veterinary medicine is not just a bystander but a powerful force for positive change, a profession that not only heals animals but also safeguards the planet for generations to come. In the words of Jane Goodall, “What you do makes a difference, and you have to decide what kind of difference you want to make.” Let us make the difference our world desperately needs.\n\n\nEthics and consent\n\nEthics and consent not required for this article.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nDey R, Lewis SC: Chapter 6 - Natural Disasters Linked to Climate Change.Trevor MBT, editor. The Impacts of Climate Change Letcher. Elsevier; 2021; pp. 177–193. Publisher Full Text\n\nFAO: Livestock Solutions for Climate Change. Food and Agricultural Organization of the United Nations, FAO; 2017. Reference Source\n\nFAO: Animal Health and Climate Change. Food and Agricultural Organization of the United Nations, FAO; 2020. Reference Source\n\nLacetera N: Impact of Climate Change on Animal Health and Welfare. Anim. Front. 2019; 9(1): 26–31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLio MS, Roberta GF, Maugeri A, et al.: How Antimicrobial Resistance Is Linked to Climate Change: An Overview of Two Intertwined Global Challenges. Int. J. Environ. Res. Public Health. 2023; 20(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nNarayan E: How Climate Change Will Affect Your Pet – and How to Help Them Cope. PreventionWeb; 2023. Reference Source\n\nRupasinghe R, Chomel BB, Martínez-López B: Climate Change and Zoonoses: A Review of the Current Status, Knowledge Gaps, and Future Trends. Acta Trop. 2022; 226: 106225. PubMed Abstract | Publisher Full Text\n\nUpadhyay RK: Markers for Global Climate Change and Its Impact on Social, Biological and Ecological Systems: A Review. Am. J. Clim. Chang. 2020; 09(3): 159–203. Publisher Full Text\n\nZiswiler V: Extinct and Vanishing Animals: A Biology of Extinction and Survival. Springer Science & Business Media; 2012."
}
|
[
{
"id": "344540",
"date": "03 Dec 2024",
"name": "I Made Dwi Mertha Adnyana",
"expertise": [
"Reviewer Expertise One Health",
"Epidemiology and Biostatistic",
"zoonotic disease"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors, The manuscript presents an important and timely perspective on the role of veterinarians in addressing climate change challenges. The manuscript addresses an important topic and provides a good foundation for discussion, but requires substantial revision to strengthen its academic rigor and practical utility.\nAbstract The first paragraph (lines 6–15) is heavily focused on problem description but lacks quantification of impacts. Specific statistics or concrete examples would strengthen the opening argument. The second paragraph (lines 16–27) discussing action steps is somewhat vague. Phrases like \"integrate climate adaptation and mitigation strategies\" need more specific examples or a clearer definition of what these strategies entail. The final paragraph (lines 28-36) could be more impactful by including specific, measurable outcomes or goals rather than general statements about building \"climate-resilient practices.\"\nKeywords The keywords (lines 261-280) are appropriate but could be more specific to help with database searches. Consider adding terms related to specific veterinary practices or climate change mitigation strategies.\nIntroduction The introduction (lines 154-239) provides a solid foundation but would benefit from more specific data and concrete examples of how climate change is already impacting veterinary practice. While the 14.5% greenhouse gas emission figure from livestock is cited, the introduction should better quantify other key impacts. Additionally, the transition between paragraphs could be improved to create better flow and logical progression of ideas.\nWhy Must Veterinary Professionals Act? In lines 689-725, the five key areas of action (zoonotic disease prevention, sustainable agriculture, biodiversity conservation, climate-resilient practices, and community leadership) are well-identified but lack specific implementation strategies. Each area would benefit from concrete examples of successful interventions or pilot programs. The manuscript should provide more detailed guidance on how veterinarians can practically implement these actions in their daily practice.\nThe Time to Act Section Lines 154-188 make broad statements about urgency but would be strengthened by including specific timelines, benchmarks, or goals for the veterinary profession. The section lacks measurable objectives that would help guide institutional and individual responses.\nReferences and Evidence Base The paper relies heavily on reports and some older references (e.g., Ziswiler 2012). More recent peer-reviewed literature should be incorporated, particularly regarding emerging climate impacts on animal health and innovative veterinary responses (Red 1 and Ref 2). The manuscript would benefit from including case studies or success stories where veterinary interventions have effectively addressed climate-related challenges.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "352442",
"date": "28 Dec 2024",
"name": "Gustavo J Nagy",
"expertise": [
"Reviewer Expertise Interdisicplinary Climate Studies. Climate Change. Environemntal Sciences. Climate Adaptation. Planetary Health."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe author analyzed the increasing role of veterinarians in the Environmental and Public Health domains beyond their traditional animal health stewards and safeguards. The author focuses on the importance of climate change, highlighting the carbon emissions from livestock and how climate change and the increasing frequency of extreme weather affect animal health by spreading vector-borne diseases. The author's strong advocacy for the One Health approach to sustainable agriculture and biodiversity conservation is a key point. This approach places veterinarians' roles at the center of One Health, enabling them to better address animal and planetary health issues beyond the traditional care of livestock. The author highlights the urgent need for climate action—both adaptation and mitigation—underscoring the pivotal role of veterinarians in managing it. He presents a list of well-known activities where veterinarians can act, which is not novel and is typically found with the assistance of AI generators. However, an Opinion Article is not that novel; it should address relevant topics, and this article does it. In this vein, the author's emphasis on a new vision of environmental protection, sustainable agriculture, Health, and biodiversity conservation calls for proactive systemic changes. Veterinarians must be proactive instead of reactive to the above mentioned issues and push for systemic changes. He mentions several relevant topics, such as the need for a new approach to teaching veterinary medicine, including carbon management and sustainable practices. The author highlights the veterinarian's capacity and responsibility to become a champion regarding the environment and animal and human Health. A One-Health approach, including allied professionals, is crucial to achieving One Health with a Planetary Vision. The author makes a common mistake (for non-climate change specialists) by using mitigation and mitigation instead of reduction/reduction, for instance, \"mitigate deforestation.\" In climate change, mitigation refers to the carbon budget (C emission-C sink) and the actions to balance them better. Finally, although the citations are correct and relatively new, they should have included a few more recent ones -from 2022 to 2024-. Also, as an \"Allied scientist\" to the One Health approach from the Earth and Environmental Sciences focused on Interdisciplinary Climate studies, I feel the need to punctuate that this Opinion Article about One Health could have put a bit more emphasis on the Planetary Health approach , which I firmly believe merges with One Health, mainly when the focus is on climate change.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "340715",
"date": "10 Jan 2025",
"name": "Robyn Alders",
"expertise": [
"Reviewer Expertise One Health",
"sustainable livestock production",
"animal health",
"disease prevention"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis opinion article addresses a crucial topic and the author is to be commended for their efforts. There is growing literature on the topic, and the author has cited only one reference for each of the key points. Given the importance of the topic, it would be ideal to include a second citation for key points. The brevity of the opinion means that some points do not receive in-depth attention. For example, there is a large and growing literature on GHG emissions from livestock with some authors questioning the robustness of some data. The Conclusions are valid. However, it would be ideal to also mention: * the importance of animal genetics to animal health. Veterinarians should encourage the raising of animals that are well-adapted to their local environments, requiring fewer inputs such as antimicrobials. See FAO 2025: Benefits from and threats to animal genetic resources; and * the need for climate-smart actions to complement actions addressing other planetary boundaries. See WOAH 2021: Planetary Boundaries and Veterinary Services.\nAdditional comments: * In the Abstract, it is suggested that \"As the stewards of animal health\" be changed to \"As stewards of animal health\". Veterinarians are not the only stewards of animal health. * Under sustainable agriculture, it would be ideal to mention that improved animal health can contribute to improved nutrient yields by reducing losses of human-edible components of animal carcases, i.e. meat and red and green offal.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1360
|
https://f1000research.com/articles/13-1359/v1
|
13 Nov 24
|
{
"type": "Research Article",
"title": "De-ethnicizing Ethiopian higher education leadership: the quest for merit-based governance",
"authors": [
"Awol Ali Mohammed"
],
"abstract": "Background This study examines the growing trend of ethnicized leadership in Ethiopian higher education institutions and advocates for a shift toward merit-based governance to improve institutional integrity and performance. Since 1991, with the introduction of ethnic federalism, leadership appointments in Ethiopian universities have increasingly been based on ethnic identity rather than qualifications. This has led to governance challenges, weakened academic standards, and reduced institutional efficiency. The study highlights the need for governance reforms prioritizing meritocracy to enhance the quality and sustainability of Ethiopia’s ethnically diverse higher education system.\n\nMethods The study utilizes a qualitative research approach, combining both primary and secondary data. Primary data were collected through semi-structured interviews with university administrators, faculty, and governance experts, while secondary data were gathered from institutional reports, government policies, and academic literature. Institutional theory, principal-agent theory, and meritocratic theory frame the analysis, providing insights into how ethnic-based leadership appointments affect university governance and performance.\n\nResults The findings reveal that ethnicized leadership has eroded governance structures, lowered academic quality, and compromised institutional efficiency. Leadership appointments based on ethnicity rather than merit have led to poor decision-making, weakened accountability, and reduced transparency. In contrast, merit-based governance improves accountability, decision-making, and institutional performance. The study emphasizes that transitioning to a meritocratic leadership model is vital for restoring institutional integrity and academic excellence in Ethiopian universities.\n\nConclusions Ethnic federalism, while initially designed to empower regions, has politicized federal institutions, including universities, reducing them to regional entities rather than national institutions. This system of ethnicized leadership has fostered a culture of favoritism, rampant corruption, and ineffective governance, ultimately weakening Ethiopia’s higher education system.\n\nRecommendations Governance reforms that prioritize merit-based appointments are urgently needed. Legal reforms, transparent leadership selection processes, depoliticization efforts, and capacity-building initiatives are recommended to foster a meritocratic culture and improve institutional performance in Ethiopian universities.",
"keywords": [
"Ethiopia",
"Higher-Education",
"Leadership-Ethnicization",
"De-Ethnicization",
"Merit-Based-Governance"
],
"content": "1. Introduction\n\nThe governance of higher education has long been recognized as a cornerstone for the development of an effective and innovative education system. Leadership, in particular, plays a pivotal role in shaping the direction, quality, and sustainability of higher education institutions (HEIs) (Alem, 2003). However, in Ethiopia, the leadership landscape within HEIs has, for decades, been influenced by ethnic affiliations rather than merit-based criteria. The practice of ethnic-based leadership appointments, commonly referred to as “ethnicization,” has raised concerns regarding the efficiency, impartiality, and academic quality within the nation’s higher education sector (Molla, 2013). This study explores the ongoing reforms aimed at de-ethnicizing Ethiopian higher education leadership and transitioning to a governance model driven by merit-based appointments. This shift is seen as a critical step towards enhancing institutional autonomy, accountability, and overall educational quality.\n\nThe Ethiopian higher education system has long been intertwined with the country’s socio-political dynamics, particularly those related to ethnic identities. Historically, the governance of universities in Ethiopia mirrored the broader political landscape, where centralization of power and ethnic favoritism has shaped leadership appointments (Ministry of Education, 2022). The establishment of the federal system in 1995, following the downfall of the Derg regime, marked the formalization of ethnic federalism, designed to address Ethiopia’s diverse ethno-linguistic groups (Vaughan & Tronvoll, 2003). This system decentralized authority to regional states and introduced ethnicity as a key criterion in political and institutional governance, including in higher education leadership (Alem, 2003).\n\nThe Ethiopian higher education system has undergone significant expansion and transformation over the past two decades. Beginning with a limited number of universities, the sector now boasts over 50 public universities and numerous private institutions (World Education News & Reviews, 2011). This growth has been driven by the government’s recognition of higher education as a key to national development, particularly in the areas of science, technology, and innovation (Alem, 2003). However, the rapid expansion has been accompanied by challenges in maintaining academic quality, institutional autonomy, and effective governance.\n\nWhile ethnic federalism was intended to balance representation and promote inclusivity, it has often resulted in leadership appointments that prioritize ethnic identity over meritocratic qualifications in academic institutions (Abbink, 2006). Universities, which should ideally be bastions of meritocratic principles, have increasingly been affected by this politicized approach, leading to leadership choices that may reflect political allegiances rather than academic excellence and integrity. This has raised concerns about the role of ethnic identity in leadership appointments, with critics arguing that it undermines the quality and independence of higher education governance (Aalen, 2011). The ethnicization of leadership, particularly in public universities, has thus become a key challenge, prompting calls for reform to safeguard academic integrity and institutional effectiveness.\n\nEthnic federalism, introduced in Ethiopia in the 1990s, created a political structure that heavily emphasized ethnic representation at all levels of government, including in higher education institutions (Abbink, 2022). This system, while intended to foster inclusion and representation, often led to the appointment of leaders based on ethnic loyalty rather than qualifications and competence (Abbink, 2006). In practice, this has hindered the meritocratic ideals of higher education, leading to inefficiencies, corruption, and a decline in academic standards (Taye & Hailu, 2016).\n\nThe ethnicization of higher education leadership is a manifestation of the broader ethnic federalism policy that Ethiopia adopted following the 1991 overthrow of the Derg regime. The Ethiopian People’s Revolutionary Democratic Front (EPRDF) introduced a political system that sought to empower ethnic groups by granting them administrative autonomy in various regions. As a result, leadership roles in higher education often mirrored the ethnic makeup of their respective regions. In many instances, ethnic loyalty overshadowed qualifications, leading to the appointment of leaders with limited experience or expertise in higher education management (Valfort, 2007).\n\nThe effects of this ethnicization have been multifaceted. Studies have documented how ethnically driven appointments have led to inefficiencies in decision-making, internal conflicts within institutions, and a focus on maintaining ethnic dominance rather than improving academic quality (Mahammoda, 2022). This system has also stifled the professional development of talented individuals who may not belong to the dominant ethnic group in their respective regions, thus limiting the diversity and competence of leadership in higher education institutions.\n\nRecognizing the limitations of ethnic-based leadership appointments, the Ethiopian government has initiated reforms aimed at transitioning to a merit-based governance model in higher education. This shift is part of a broader effort to enhance the quality of education and align the sector with global standards. The Ministry of Education has articulated the need for leadership appointments to be based on qualifications, experience, and proven competence in managing academic institutions (Ministry of Education, 2023). By de-ethnicizing leadership, the government seeks to foster a more inclusive, transparent, and accountable system of governance within HEIs.\n\nMerit-based governance is premised on the idea that leadership positions should be filled by individuals who possess the necessary skills, knowledge, and experience to guide institutions towards achieving their academic and developmental goals (Altbach, 2016). In the context of Ethiopian higher education, this involves ensuring that leaders are selected through a competitive, transparent process that prioritizes merit over ethnic affiliation. The shift towards merit-based governance is also seen as essential for restoring institutional autonomy and reducing the influence of external political factors on university operations (Gasman et al., 2015).\n\nThe transition to merit-based leadership has significant implications for the quality and accountability of Ethiopian higher education. Studies have shown that leadership plays a crucial role in shaping the academic culture of institutions, influencing faculty performance, student outcomes, and research productivity (Leithwood et al., 2020). In Ethiopia, the current reforms are expected to improve institutional governance, enhance resource management, and foster a more supportive environment for academic excellence.\n\nAccountability is another critical aspect of the reform process. Under the previous system, leaders were often shielded from accountability due to their ethnic ties and political affiliations. By introducing merit-based governance, the government aims to establish a system where leaders are held accountable for their decisions and the performance of their institutions. This is expected to improve transparency and reduce instances of corruption and mismanagement within HEIs (Muadin and Akmalia, 2022).\n\nMerit-based governance is fundamental for the effectiveness, accountability, and integrity of higher education institutions. In academic contexts, meritocratic systems ensure that leaders are chosen based on their qualifications, experience, and achievements, rather than political or ethnic affiliations. This approach not only promotes competence and fairness but also reinforces institutional autonomy, a critical feature of thriving academic environments (Altbach, 2011).\n\nIn Ethiopian higher education, where ethnic considerations have often influenced leadership appointments, merit-based governance is crucial to restoring public confidence in academic institutions. It ensures that the most capable individuals are placed in leadership positions, fostering innovation, academic freedom, and effective management of resources (Teshome, 2007). Moreover, universities led by competent and experienced leaders are better positioned to produce high-quality research, foster student development, and contribute meaningfully to national development. The absence of a meritocratic system can lead to leadership inefficiencies, reduced institutional accountability, and the erosion of academic standards, ultimately affecting the reputation and performance of the higher education sector.\n\nThe Ethiopian government is committed to de-ethnicizing higher education leadership through reforms aimed at establishing merit-based governance model. The project of de-ethnicizing Ethiopian higher education leadership would become a challenging task. One of the primary obstacles is the deeply entrenched ethnic-based political culture in Ethiopia. Ethnic identity remains a powerful determinant of social and political power, and attempts to reform leadership structures have been met with resistance from groups that benefit from the current system. Additionally, there are concerns about the potential for merit-based appointments to be manipulated or influenced by political elites, particularly in regions where ethnic tensions remain high.\n\nAnother challenge lies in the capacity of the higher education system to identify and develop leaders with the necessary qualifications and experience. Ethiopia’s higher education sector has historically lacked robust leadership development programs, and there are concerns about the availability of qualified candidates to fill leadership roles under a merit-based system. Addressing these challenges will require a concerted effort by the government, universities, and other stakeholders to build the capacity of the higher education system to support merit-based governance.\n\nTherefore, the primary objective of this study is to examine how ethnicization affects leadership appointments within Ethiopian higher education, and to analyze the importance of implementing merit-based governance to enhance institutional integrity and effectiveness. The study aims to delve into the historical and political factors that have influenced the ethnicization of leadership in Ethiopian universities, revealing how ethnic-based appointments impact governance structures, academic performance, and the overall quality of institutions. Additionally, the study seeks to explore how merit-based governance could foster greater accountability, transparency, and improved institutional performance. Finally, it aims to propose strategies for promoting a meritocratic leadership system, considering Ethiopia’s complex ethnic and political dynamics. By addressing these objectives, the study contributes to ongoing discussions about reforming university governance in Ethiopia and highlights the broader implications for national development. Specifically, the study seeks to:\n\n• Explore the historical and political factors that have contributed to the ethnicization of leadership in Ethiopian universities.\n\n• Evaluate the effects of ethnic-based leadership appointments on institutional governance, academic performance, and overall institutional quality.\n\n• Examine the role of merit-based governance in enhancing the accountability, transparency, and performance of higher education institutions in Ethiopia.\n\n• Propose strategies for promoting a meritocratic system in university leadership, considering Ethiopia’s complex ethnic and political landscape.\n\nThe outcome of this study is significant for several reasons. First, it directly impacts the governance and quality of higher education, with long-term effects on the sector’s ability to contribute to national development. Second, understanding the consequences of ethnic-based appointments provides valuable insights into the broader socio-political challenges facing Ethiopia, where ethnic identities often intersect with governance structures. Finally, promoting merit-based governance in universities can serve as a model for other public institutions, encouraging a shift towards competence and fairness in leadership across sectors.\n\n\n2. Theoretical framework\n\nThis study is grounded in three interrelated theoretical perspectives—institutional theory, principal-agent theory, and meritocratic theory—that collectively provide a comprehensive understanding of the shift from ethnic-based to merit-based leadership in Ethiopian higher education.\n\nInstitutional theory posits that the structures and practices of institutions significantly shape the behavior of individuals within those institutions. Meyer and Rowan (1977) argue that formal rules and organizational structures play a crucial role in aligning educational governance with global standards. This theory is particularly relevant in the context of Ethiopian higher education reforms, where institutional frameworks have historically influenced leadership practices.\n\nIn Ethiopia, higher education has been heavily impacted by ethnic-based leadership, resulting in inefficiencies and a lack of accountability (Teferra & Altbach, 2004). Institutional theory provides insights into how reforming these structures can facilitate the adoption of best practices and enhance accountability and governance. By focusing on the institutional frameworks guiding higher education, this theory elucidates how changes in leadership can be implemented systematically, ensuring that the new merit-based system is not only adopted but also sustained over time.\n\nIn addition, Principal-agent theory offers a lens to analyze the relationships of accountability and control between leaders (agents) and the government or public (principals) (Jensen & Meckling, 1976). In the Ethiopian context, the transition from ethnic-based to merit-based leadership is critical for addressing accountability deficits that have characterized higher education leadership.\n\nEthnic-based leadership has often led leaders to prioritize personal or group interests over institutional goals, undermining public trust and institutional effectiveness (World Bank, 2017). By applying principal-agent theory, this study examines how a merit-based system can enhance accountability by clarifying the expectations and responsibilities of leaders. This shift allows for a more transparent evaluation of leaders’ performance based on objective criteria, thereby aligning their actions with the interests of the institutions and their stakeholders. The clarity introduced by this framework is vital for ensuring that leaders are held accountable for their decisions and actions, fostering a culture of responsibility and integrity.\n\nOn the other hand, Meritocratic theory emphasizes that leadership positions should be awarded based on competence, skills, and qualifications rather than external factors such as ethnicity, political affiliation, or personal connections (Young, 2017). This theory provides a normative foundation for the reforms currently taking place in Ethiopia, advocating for fairness, transparency, and competence in leadership appointments.\n\nThe meritocratic approach is significant in a multicultural society like Ethiopia, where ethnic identities have historically dictated leadership roles. By transitioning to a merit-based system, this study seeks to demonstrate how such reforms can lead to more equitable representation in leadership positions, promoting inclusivity and fairness among diverse groups. The meritocratic perspective underscores the importance of establishing criteria for leadership that prioritize qualifications and proven capabilities, which can enhance the overall effectiveness of higher education institutions.\n\nThe selection of these theories is justified by their complementary strengths in addressing the challenges faced by Ethiopian higher education during this transformative period. Institutional theory provides a structural lens to understand how changes can be implemented within existing frameworks, principal-agent theory offers insights into enhancing accountability and performance management, and meritocratic theory establishes a normative basis for the reforms aiming to create a more just and competent leadership landscape.\n\nTogether, these theories provide a robust analytical framework that not only explains the motivations behind the shift from ethnic-based to merit-based leadership but also informs practical approaches to implementing and sustaining these reforms. By leveraging these perspectives, this study contributes to the broader discourse on governance and accountability in higher education, particularly within the Ethiopian context, while also offering valuable insights for similar transitions in other multicultural societies.\n\n\n3. Methods\n\nThis study adopts a qualitative research approach, which is particularly well-suited for exploring complex social phenomena such as leadership dynamics in Ethiopian higher education. Qualitative research allows for an in-depth understanding of the perceptions, experiences, and contextual factors that influence governance practices. As Creswell and Poth (2018) assert, qualitative methods facilitate the exploration of meanings and interpretations that individuals assign to their experiences. In the context of this research, it is essential to delve into how ethnic affiliations shape leadership roles and decision-making processes within higher education institutions. By focusing on qualitative data, the study aims to capture the rich narratives of participants, providing insights into the underlying issues related to de-ethnicization and merit-based governance.\n\nThe research employed a case study design, which enables a comprehensive examination of specific higher education institutions in Ethiopia. This design is particularly effective for understanding the intricate relationships between leadership styles and governance structures within their unique contexts. According to Yin (2018), case studies allow researchers to explore real-life situations in depth, making them ideal for investigating complex issues like ethnic considerations in leadership. By selecting multiple institutions as case studies, the research will gather diverse perspectives and experiences, facilitating a nuanced understanding of how merit-based governance can be achieved in a historically ethnicized landscape.\n\nTo ensure a robust analysis, data were collected from multiple sources, which enhance the validity of the findings through triangulation. First, semi-structured interviews were conducted with university leaders, faculty members, and administrative staff. These interviews provide insights into their experiences and perspectives on leadership practices and the influence of ethnicity on governance. Additionally, focus group discussions (FGDs) have been organized with students and alumni to capture their views on leadership dynamics and their experiences within these institutions. The researcher utilized an interview guide and informed consent to conduct the interviews and focus group discussions (Mohammed, 2024a). Such discussions are valuable for generating collective insights and fostering dialogue among participants. Finally, document analyses were employed on institutional reports, government policies, and academic literature (Mohammed, 2024b). This analysis was contextualizing the findings within the broader educational landscape and highlight existing frameworks that either support or hinder merit-based governance.\n\nTo enhance the quality and rigor of this research project, a purposive sampling strategy has been employed to select participants who possess relevant experience or knowledge about higher education leadership in Ethiopia. This approach ensures that diverse perspectives are included in the study, enriching the data collected. To refine questions and improve clarity, pilot testing of interview guides and focus group discussion prompts will be conducted with a small group prior to full implementation. This step is crucial for identifying potential issues in question formulation or participant comprehension. Furthermore, reflexivity play an important role throughout the research process; maintaining a reflexive journal will allow the researcher to document personal biases, assumptions, and reflections on how these may influence data interpretation.\n\nThe tools for data collection include semi-structured interviews, focus group discussion guides, and document review checklists. Semi-structured interviews will facilitate open-ended responses while ensuring that key topics related to leadership practices are covered (Mohammed, 2024c). An interview guide will be developed based on the research questions to maintain focus while allowing participants to express their thoughts freely. Focus group discussions will also be guided by structured questions designed to stimulate dialogue among participants about their experiences regarding governance and leadership. Document review checklists help systematically analyze institutional documents relevant to leadership practices, ensuring that critical information is not overlooked.\n\nData analysis involves several systematic steps to ensure rigorous examination of the collected data. Initially, all interviews and focus group discussions will be transcribed verbatim to accurately represent participants’ voices. Thematic analysis will then be employed to identify recurring themes and patterns related to leadership practices and ethnic influences (Braun & Clarke, 2006). This method allows for a flexible approach to analyzing qualitative data while providing a clear framework for interpreting findings. Additionally, narrative analysis may be utilized to explore individual stories that illuminate the complexities surrounding de-ethnicization in leadership. By focusing on personal narratives, this approach can reveal deeper insights into how individuals navigate their identities within institutional frameworks.\n\nEthical considerations are paramount throughout the research process to ensure the integrity of the study and the protection of participants’ rights. Informed consents were obtained from all participants prior to data collection, ensuring they understand the purpose of the study and their rights regarding participation (Mohammed, 2024a). Confidentiality will be maintained by anonymizing participant data and securely storing all information collected during the research process. Participants will also have the right to withdraw from the study at any time without facing any penalties or repercussions. These ethical guidelines are essential for fostering trust between researchers and participants while ensuring that the research adheres to established ethical standards.\n\nTherefore, this comprehensive qualitative methodology aims not only to provide valuable insights into the quest for merit-based governance in Ethiopian higher education leadership but also to address the challenges posed by ethnic considerations within this context. By employing a multi-faceted approach that includes diverse data sources and rigorous analytical techniques, this study seeks to contribute significantly to understanding how Ethiopian higher education can move towards more equitable governance structures.\n\nEthics and consent\n\nThe research adhered to stringent ethical standards to protect participants and maintain the integrity of the research process. Written consent was obtained from all participants, who were fully informed about the nature, purpose, and potential risks of the study before agreeing to participate. In this study, informed consent was obtained from all participants. Written consent was secured to ensure that participants fully understood the study’s purpose, procedures, and their rights, including the right to withdraw at any time without consequence. The study adhered to all ethical guidelines as approved by the ethical review committee, and no waiver of consent was granted. If verbal consent had been used, it would have been clearly documented along with the reasons for this approach, and such a procedure would have been explicitly approved by the ethics committee. However, in this study, written consent was used to maintain rigorous ethical standards. This ensured that participants were aware of their rights, including the right to withdraw from the study at any time without consequences (Orb, Eisenhauer, & Wynaden, 2001).\n\nConfidentiality and anonymity were strictly maintained throughout the research process. Identifying information was removed from transcripts, and data was securely stored to prevent unauthorized access. This approach was essential for protecting the privacy of participants and ensuring the ethical conduct of the research (Wiles, 2012). This study received full ethical approval from the Institutional Review Board (IRB) of College of Law and Governance, which comprises five members. The approval was granted on 10/02/2024 with number GaDS-307/2024. All procedures involving human participants were conducted in strict adherence to the Declaration of Helsinki to ensure the ethical integrity of the research.\n\n\n4. Result and Discussion\n\nThe ethnicization of leadership in Ethiopian universities has deep historical and political roots, shaped by the broader socio-political dynamics of the country. The foundation for ethnic-based leadership in higher education is closely linked to the establishment of the Ethiopian state and the subsequent evolution of its political systems. Understanding these factors requires an examination of both the imperial and post-revolutionary periods, culminating in the adoption of ethnic federalism in 1995, which entrenched ethnicity as a key criterion in governance, including in educational institutions.\n\nHistorically, Ethiopia’s governance was characterized by highly centralized rule, especially during the reign of Emperor Haile Selassie I (1930–1974). Higher education institutions, established during this period, reflected the imperial hierarchy, with leadership positions often dominated by elites from the central government or individuals with ties to the monarchy. Ethnic considerations, though present, were not as pronounced during this era, as the leadership of institutions like Addis Ababa University was more focused on loyalty to the state than on ethnic identity (Marcus, 1994). The imperial regime’s centralized governance, however, laid the groundwork for the political manipulation of leadership appointments in all sectors, including education.\n\nThe 1974 Ethiopian Revolution, which led to the rise of the Derg regime, drastically altered the political landscape. The Derg’s Marxist ideology emphasized class struggle and sought to suppress ethnic identities in favor of a unified socialist state. However, the Derg’s brutal governance and the marginalization of ethnic groups, particularly in the periphery, exacerbated ethnic tensions (Young, 1998). This period also saw increased state control over universities, with leadership appointments reflecting the regime’s ideological and political priorities rather than academic or managerial merit. Despite the Derg’s attempt to minimize ethnic divisions, the regime’s policies inadvertently contributed to the rise of ethno-regional movements, which would later influence the trajectory of university governance.\n\nThe most significant shift occurred following the fall of the Derg in 1991 and the rise of the Ethiopian People’s Revolutionary Democratic Front (EPRDF). The EPRDF’s adoption of ethnic federalism, enshrined in the 1995 constitution, fundamentally restructured the Ethiopian state along ethno-linguistic lines. Ethnic federalism was introduced as a means to address the long-standing grievances of marginalized ethnic groups and to provide a framework for self-determination (Vaughan, 2003). While this system was intended to promote inclusivity and regional autonomy, it also institutionalized ethnicity as a key factor in political appointments and decision-making processes, including in the leadership of higher education institutions (Abbink, 2006).\n\nUnder the EPRDF, universities became increasingly politicized, with leadership appointments often reflecting the ethnic and political allegiances of the ruling coalition. Ethnic-based appointments were justified as a means of ensuring equitable representation for Ethiopia’s diverse ethnic groups. However, critics argue that these appointments prioritized political loyalty and ethnic identity over merit, resulting in leadership that may lack the academic qualifications or managerial skills necessary for effective governance (Aalen, 2011). As a result, the ethnicization of leadership within universities mirrored the broader ethnic federalism model, reinforcing divisions and sometimes leading to ethnic favoritism in resource allocation and decision-making within institutions.\n\nSimilarly, interview results confirmed as follows:\n\n\"The ethnicization of leadership has roots in Ethiopia’s political history, particularly with the establishment of ethnic federalism in the 1990s. This political framework not only decentralized governance but also embedded ethnic identity into key sectors, including higher education. Leadership positions in universities started reflecting the ethnic composition of their respective regions, often at the expense of merit and academic qualifications. Over time, this practice has become institutionalized\" (KII, Addis Ababa, 2024).\n\nMoreover, the ethnicization of university leadership became particularly visible in the appointment of university presidents and senior administrators. In many cases, these appointments were based on ethnic representation, where leaders from dominant ethnic groups in specific regions were appointed to reflect the ethnic composition of the regional state, rather than the needs of the academic institution itself (Teshome, 2007). This approach often undermined meritocratic principles, leading to inefficiencies in university governance and a decline in institutional autonomy. Universities, which should ideally function as spaces of intellectual freedom and academic excellence, became subject to political manipulation, with leadership reflecting the political calculations of the ruling party.\n\nIn the same vein, primary data sources confirmed as follows:\n\nThe ethnic-based political structure, especially after the introduction of the 1995 Constitution, profoundly influenced leadership appointments in all sectors, including education. Universities, as state-funded institutions, were no exception. Ethnic representation was viewed as a way to distribute power, but this approach slowly overshadowed the need for competence in leadership roles (Interview, Policy Expert, Addis Ababa, 2024).\n\nSimilarly, focus group participants’ unequivocally confirmed as follows:\n\nIt’s clear that leadership in universities often mirrors the political dynamics of the country. Ethnic loyalty has frequently taken precedence over leadership ability. This practice, though initially introduced to promote inclusiveness, has created barriers for individuals who may be more qualified but do not belong to the dominant ethnic group in the region.” “We have observed how ethnicity influences decisions beyond appointments, often affecting the day-to-day governance of institutions. Ethnic favoritism impacts funding allocations, staffing decisions, and even academic promotions. This practice erodes institutional meritocracy, limiting opportunities for those not aligned with the ethnic majorities and non-territorial people (FGD, Hawassa, 2024).\n\nThe consequences of ethnic-based leadership appointments have been widely debated. On one hand, proponents of ethnic federalism argue that such appointments ensure representation and inclusivity for all of Ethiopia’s diverse groups, preventing the historical marginalization of minority communities (Merera, 2003). On the other hand, critics contend that ethnicization undermines the quality of governance and academic performance in universities, as leaders may be chosen for their ethnic or political affiliations rather than their qualifications or vision for the institution (Berhanu & Woldehanna, 2021). This dynamic has led to a leadership crisis in many Ethiopian universities, where the emphasis on ethnic identity over merit has resulted in poor governance, reduced academic standards, and limited institutional development.\n\nThe study findings on the reveal a complex interplay of factors rooted in institutional theory, principal-agent theory, and meritocratic theory. This context reflects the legacy of political dynamics that have historically favored certain ethnic groups over others, influencing who rises to positions of authority. Additionally, principal-agent theory elucidates the relationships between university leadership and stakeholders, highlighting how ethnic affiliations can impact accountability and governance, often resulting in a misalignment of interests where leaders prioritize ethnic loyalty over institutional objectives. Furthermore, meritocratic theory challenges the notion of a purely merit-based system by exposing how historical and political legacies can skew the selection process, allowing leaders to ascend based not only on qualifications but also on their ethnic background and political connections. Collectively, these theoretical frameworks illuminate the multifaceted nature of ethnic leadership in Ethiopian universities, revealing the need for a nuanced understanding of how historical and political contexts shape institutional dynamics.\n\nThe ethnic-based leadership structure in Ethiopian universities has had profound consequences on governance, academic performance, and overall institutional quality. As leadership appointments in public universities have increasingly reflected ethnic identities and political allegiances, there are concerns that this approach undermines the core principles of meritocracy and institutional autonomy. The reliance on ethnic-based appointments has fostered inefficiencies in governance, weakened academic standards, and compromised the mission of universities to serve as independent centers of knowledge and innovation. In this context, the intersection of ethnicity and leadership has negatively affected governance, academic performance, and institutional quality in multiple ways.\n\n4.2.1 Governance and Institutional Autonomy\n\nThe governance of Ethiopian universities, particularly public institutions, has been significantly influenced by ethnic-based leadership appointments, which are often guided by political considerations. These appointments have undermined the autonomy of universities by making them subject to external political pressures. University leadership, instead of being chosen based on merit, is often a reflection of the dominant ethnic group in the region where the university is located or aligned with the ruling coalition’s political calculations (Aalen, 2011). As a result, the autonomy of these institutions is compromised, with leaders sometimes serving the interests of political elites rather than prioritizing academic excellence and institutional development.\n\nEthnic-based leadership can lead to centralized decision-making that does not adequately reflect the needs of the academic community. Instead of promoting participatory governance, which is essential for the effective management of higher education institutions, leaders may focus on consolidating power within specific ethnic or political groups, limiting the space for diverse perspectives and academic freedom (Teshome, 2007). In some cases, ethnic favoritism may influence key decisions such as faculty appointments, promotions, and resource allocation, leading to imbalances and inefficiencies in the administration of the university. This dynamic contributes to a governance structure where ethnic identity becomes more significant than institutional goals, resulting in a lack of transparency, accountability, and long-term planning (Abbink, 2006).\n\nFurthermore, ethnic-based leadership in universities exacerbates the fragmentation of the academic environment, leading to divisions within faculties and among students. When leadership is perceived as ethnically biased, it can create a sense of exclusion among groups that are not represented in the leadership structure, fostering mistrust and conflict. This politicization of leadership diminishes the collaborative environment necessary for research and learning, ultimately harming institutional governance and cohesion (Teferra, 2014). The lack of institutional autonomy and the politically driven nature of university governance in Ethiopia have significantly weakened the ability of universities to function as independent and high-performing academic institutions.\n\nConsistent with the above assertions, primary interview results confirmed as follows:\n\nThe ethnicization of leadership has severely undermined governance in Ethiopian universities. Leadership appointments driven by ethnic identity rather than merit lead to inefficiencies in decision-making. Many leaders prioritize ethnic interests over institutional goals, resulting in weak governance structures. This has led to fragmented decision-making and inconsistent academic standards. One of the most damaging effects of ethnic-based leadership is the lack of trust it fosters within the institution. Staff and students perceive decisions—whether about funding, hiring, or curriculum changes—as biased, which diminishes institutional cohesion. This lack of trust extends beyond the university, affecting collaborations with other institutions and international bodies\" (Interview, Hawassa, 2024).\n\n4.2.2 Academic Performance and Institutional Quality\n\nEthnic-based leadership has also had detrimental effects on the academic performance and quality of Ethiopian universities. One of the core challenges is that ethnic-based appointments often prioritize political loyalty and ethnic representation over academic qualifications and managerial competence. This approach leads to leadership that may lack the necessary expertise to promote a high standard of academic performance and research (Berhanu & Woldehanna, 2021). The absence of a meritocratic system means that university leaders are often unprepared to meet the academic, financial, and administrative challenges of running a higher education institution, which requires a combination of academic knowledge, leadership skills, and managerial experience.\n\nIn similar vein, focus group discussion results attested as follows:\n\nWe have seen how academic performance has deteriorated in institutions where ethnic-based appointments dominate. Students feel disillusioned when they observe leaders prioritizing their ethnic group over the university’s broader objectives. Academic integrity is compromised, and there is less motivation among students to excel when favoritism becomes institutionalized. The overall institutional quality suffers when ethnicity is the basis for leadership appointments. In our experience, leaders who are not necessarily the most qualified are often ineffective in addressing the challenges facing higher education, such as research development, academic freedom, and quality of instruction. This directly impacts the global standing and academic competitiveness of Ethiopian university (FGD, 2024, Addis Ababa, 2024).\n\nAs a consequence, the academic performance of universities has suffered. When leadership is focused on ethnic considerations rather than academic achievement, the emphasis on research, innovation, and academic rigor may decline. University leaders who are appointed for their political or ethnic affiliations may not prioritize the development of strong academic programs or support for faculty and students to engage in high-quality research (Woldemariam, 2018). This lack of focus on academic excellence can lead to lower standards of teaching, diminished research output, and a decline in the university’s reputation both nationally and internationally.\n\nMoreover, ethnic-based leadership affects the allocation of resources within universities, often resulting in inequitable distribution that prioritizes the interests of certain ethnic groups or political factions. This imbalance undermines the overall quality of the institution, as resources may not be directed towards the most critical academic or infrastructural needs (Ayenew, 2019). In some cases, ethnic favoritism in leadership has also been linked to corruption, where resources are misallocated or siphoned off for political or personal gain, further eroding the quality of education and institutional development (Yigremew, 2016).\n\nThe quality of university governance and academic standards are further compromised by the fact that ethnic-based leadership encourages a culture of dependency on external political actors. Instead of fostering internal mechanisms for quality assurance and institutional development, universities become reliant on political patronage to secure funding and other resources (Teferra, 2017). This dependency stifles the innovative capacity of the institutions and limits their ability to implement long-term strategies for academic and infrastructural growth. As a result, Ethiopian universities are often ranked lower compared to their counterparts in other African countries, reflecting the broader impact of ethnicized leadership on institutional quality (Ashcroft, 2018).\n\n4.2.3 Long-Term Implications for Higher Education in Ethiopia\n\nThe long-term implications of ethnic-based leadership in Ethiopian universities are far-reaching. If not addressed, the continued politicization of university governance may result in further deterioration of academic standards and institutional integrity. Ethiopia’s higher education system, which has expanded rapidly in recent years, may fail to fulfill its potential in contributing to national development and producing globally competitive graduates (Altbach, 2011). Moreover, the lack of merit-based governance threatens the ability of Ethiopian universities to attract and retain top academic talent, both within the country and from the international academic community.\n\nTo mitigate these effects, there is a pressing need to reform the system of leadership appointments in Ethiopian universities. Merit-based governance, where leaders are chosen based on their academic credentials and managerial competence rather than ethnic identity, is crucial for restoring the integrity and effectiveness of the higher education system. Implementing transparent and meritocratic recruitment processes would not only improve governance but also enhance the quality of academic programs, research output, and institutional development (Teshome, 2007). Ultimately, shifting away from ethnic-based leadership is essential for Ethiopian universities to regain their role as independent institutions dedicated to academic excellence and national progress.\n\nThe findings highlight the intricate relationship between ethnic leadership and institutional performance, drawing upon institutional theory, principal-agent theory, and meritocratic theory. Ethnic-based leadership often leads to governance challenges, as institutional theory suggests that entrenched ethnic affiliations can create divisions and foster an environment of favoritism, undermining collaborative decision-making processes essential for effective governance. This fragmentation may inhibit academic excellence by perpetuating unequal access to resources and opportunities, as leaders may prioritize the interests of their ethnic group over the collective goals of the university. Principal-agent theory further illustrates how the alignment of interests between ethnic leaders and their constituents can skew accountability, leading to potential neglect of broader institutional responsibilities in favor of ethnic loyalty. Conversely, meritocratic theory emphasizes the potential drawbacks of ethnic leadership in promoting a merit-based culture, where academic qualifications and achievements may be overshadowed by political and ethnic considerations in leadership appointments. Ultimately, these theoretical perspectives collectively underscore the need for a reevaluation of leadership structures in Ethiopian universities, advocating for a governance model that transcends ethnic affiliations to foster an environment conducive to academic excellence and institutional integrity.\n\nThe implementation of merit-based governance in Ethiopian higher education institutions has the potential to transform university leadership by significantly improving accountability, transparency, and overall institutional performance. In contrast to ethnic-based appointments, where leadership roles are often determined by political or ethnic considerations, merit-based governance prioritizes the academic qualifications, experience, and leadership skills of individuals, thereby ensuring that the most competent and capable leaders are appointed to key positions. This shift could strengthen institutional governance and academic standards, fostering a more transparent and accountable educational environment, essential for the long-term development of Ethiopia’s higher education system.\n\n4.3.1 Merit-Based Governance and Accountability\n\nMerit-based governance is crucial for enhancing accountability within Ethiopian higher education institutions. Accountability refers to the responsibility of university leaders to manage institutional resources effectively, implement policies that align with academic goals, and ensure that the university operates in the best interest of students, faculty, and the broader community. A meritocratic leadership system can create a culture of responsibility by ensuring that leaders are selected based on their ability to meet the institution’s academic and administrative needs (Altbach, 2011). This approach encourages a results-oriented management style, where leaders are held accountable for their decisions and are expected to deliver measurable improvements in institutional performance.\n\nIn contrast, ethnic-based leadership can erode accountability as leaders may feel more beholden to political elites or ethnic constituencies than to the university community. Ethnic loyalties can create a situation in which leaders are not evaluated based on their effectiveness but on their ability to satisfy ethnic or political demands. This undermines the institution’s capacity to hold leaders accountable for poor performance or mismanagement, leading to a culture of impunity (Teferra, 2014). On the other hand, merit-based governance ensures that leaders are chosen based on their ability to uphold the institution’s mission, promote academic excellence, and manage resources efficiently. This focus on competence and integrity creates a governance structure that promotes accountability at all levels of the institution.\n\nMoreover, when leadership appointments are made through transparent, merit-based processes, it becomes easier for stakeholders—including faculty, students, and external bodies—to hold university leaders accountable for their actions. Leaders selected on merit are more likely to implement mechanisms for monitoring and evaluating institutional performance, such as audits, reviews, and feedback systems, which are essential for creating a culture of accountability (Ashcroft, 2018). These measures ensure that universities operate with greater transparency, reducing the opportunities for corruption, mismanagement, and nepotism that have been associated with ethnic-based leadership (Yigremew, 2016).\n\n4.3.2 Merit-Based Governance and Transparency\n\nTransparency is another critical element that can be significantly improved through merit-based governance. Transparency in higher education institutions refers to the openness and clarity with which decisions are made, resources are allocated, and policies are implemented. Merit-based governance encourages transparent decision-making processes, particularly in areas such as leadership appointments, resource distribution, and academic promotions. When leaders are chosen based on their academic credentials and experience, there is less room for favoritism or manipulation in the decision-making process, leading to a more open and fair environment (Berhanu & Woldehanna, 2021).\n\nIn Ethiopian universities, ethnic-based leadership appointments often occur through opaque processes that are difficult to scrutinize. This lack of transparency can lead to distrust within the academic community and foster a perception that university leaders are not acting in the institution’s best interest but rather serving the interests of external political actors (Teshome, 2007). Merit-based governance, however, promotes transparency by making the criteria for leadership appointments clear and ensuring that all decisions are based on objective standards. This transparency not only improves the morale of the academic community but also strengthens public trust in higher education institutions.\n\nBy fostering transparency, merit-based governance can also improve the allocation of resources within universities. In institutions where leadership is based on merit, resources such as funding, research grants, and academic positions are more likely to be distributed based on need and merit rather than ethnic affiliation or political connections (Ayenew, 2019). Transparent allocation of resources ensures that all departments and faculties within the university have equal access to the tools they need to succeed, thus improving the overall quality of education and research. Additionally, transparent governance structures make it easier to detect and prevent corrupt practices, further enhancing the integrity of the institution (Yigremew, 2016).\n\n4.3.3 Merit-Based Governance and Institutional Performance\n\nThe most significant impact of merit-based governance is its potential to improve the performance of Ethiopian higher education institutions. Institutional performance, in this context, refers to the university’s ability to meet its academic and administrative goals, including the delivery of high-quality education, the production of cutting-edge research, and the efficient management of resources. Merit-based governance ensures that university leaders have the necessary skills and qualifications to manage the institution effectively, thereby improving overall performance (Altbach, 2011). Leaders selected through meritocratic processes are more likely to have a clear vision for the institution’s future and the capacity to implement strategies that enhance academic and research excellence.\n\nEthnic-based leadership, on the other hand, often results in leaders who may lack the academic background or managerial competence to effectively run a university. This can lead to poor decision-making, inefficiencies in administration, and a decline in academic standards. For example, leaders who are appointed based on ethnic or political affiliations may prioritize short-term political gains over long-term institutional development, which can have a detrimental effect on the university’s ability to achieve its academic mission (Teferra, 2017). By contrast, merit-based governance ensures that leaders are selected based on their ability to improve institutional performance, which includes enhancing academic programs, supporting faculty development, and investing in research and innovation.\n\nFurthermore, merit-based governance contributes to a more competitive and dynamic academic environment. When university leadership is based on merit, it sets a standard for excellence that permeates throughout the institution. Faculty members are encouraged to pursue excellence in teaching and research, knowing that promotions and rewards are based on merit rather than political connections or ethnic background (Woldemariam, 2018). This meritocratic culture not only improves individual performance but also enhances the overall reputation of the university, making it more attractive to talented faculty, students, and international collaborators.\n\nIn addition to improving academic standards, merit-based governance has the potential to enhance administrative efficiency within Ethiopian universities. Competent leaders are better equipped to manage financial resources, streamline administrative processes, and implement policies that promote long-term institutional growth. Effective leadership, combined with transparent governance practices, ensures that universities can operate more efficiently, reduce wastage, and maximize the use of available resources for academic and infrastructural development (Ashcroft, 2018).\n\nThe findings underscore the crucial role of meritocratic principles in fostering effective governance and improving institutional performance. Drawing from institutional theory, the research highlights how entrenched practices and norms within Ethiopian universities can impede the implementation of merit-based frameworks, often leading to inefficiencies and a lack of transparency. By emphasizing accountability, merit-based governance challenges the existing ethnic-based leadership paradigms, as principal-agent theory illustrates how aligning the interests of leaders and stakeholders through performance metrics can enhance overall accountability. This alignment fosters a culture where leaders are held responsible for their actions and decisions, ultimately driving better outcomes for the institution. Furthermore, meritocratic theory posits that prioritizing qualifications and competencies over ethnic affiliations can cultivate a more equitable and productive academic environment, enabling a diverse array of talents to contribute to the institution’s success. Collectively, these theoretical frameworks advocate for a transformative shift towards merit-based governance in Ethiopian higher education, emphasizing that such an approach not only enhances accountability but also elevates academic performance and institutional integrity.\n\nConsistent with the above assertions, interview and focus group discussion results attested as follows:\n\nMerit-based governance can bring substantial improvements in accountability and performance. When leaders are appointed based on their academic qualifications and managerial experience, they are more likely to uphold principles of transparency and accountability. This creates a governance system where decisions are scrutinized, and leaders are held responsible for the outcomes of their policies (Interview with Senior Faculty Member Hawassa, 2024).\n\nSimilarly educations reform experts underlined that:\n\nIn institutions where merit-based leadership is practiced, we observe enhanced transparency in decision-making processes. These leaders tend to implement clear governance frameworks, conduct regular audits, and establish performance metrics that align with institutional goals. Accountability is a cornerstone of such systems, leading to overall institutional performance improvement (Interview, Educational Reforms Expert, 2024)\n\nOn the other hand, Focus Group Discussion results shows confirmed that:\n\nWe’ve witnessed that merit-based leaders foster a culture of responsibility. These leaders establish clear expectations, and their decisions are more transparent. Performance evaluations are fairer, and there is greater trust in the institution’s leadership. This trust permeates throughout the institution, leading to better collaboration between departments and improved academic output (FGD, Hawassa, 2024)\n\nPromoting a meritocratic system in Ethiopian higher education institutions requires a comprehensive, multifaceted approach that addresses both the internal governance structures of universities and the broader ethnic and political landscape of the country. Given the challenges posed by Ethiopia’s diverse ethnic makeup and politicized governance framework, the successful implementation of meritocracy in university leadership must be carefully tailored to mitigate ethnic tensions and political interference. This proactive approach involves institutional reforms, legal frameworks, inclusive leadership practices, and sustained political will to transform the current leadership selection processes into systems that prioritize competence, accountability, and transparency.\n\n4.4.1 Institutional Reforms and Capacity Building\n\nA key strategy for implementing meritocracy in Ethiopia’s higher education is institutional reform that strengthens the governance structures of universities. Central to this is the establishment of clear and transparent criteria for leadership appointments, emphasizing academic qualifications, managerial experience, and ethical integrity. These reforms must be institutionalized to ensure that leadership positions are filled based on merit rather than political or ethnic considerations (Altbach, 2011). Universities need to adopt comprehensive recruitment and selection processes that include clear job descriptions, standardized assessment criteria, and public vetting procedures to minimize the potential for favoritism or political interference.\n\nAdditionally, capacity building is essential for developing a pool of qualified candidates for leadership roles. Continuous professional development programs for academic staff, administrators, and potential leaders should be prioritized. Such programs could focus on leadership training, financial management, academic governance, and ethical decision-making to ensure that candidates possess the skills necessary to manage higher education institutions effectively (Ashcroft, 2018). A meritocratic system cannot function without a robust pipeline of capable leaders, and capacity-building efforts can help ensure that Ethiopia’s universities have a pool of competent candidates who are ready to take on leadership roles.\n\nTo support these institutional reforms, universities must develop mechanisms for internal accountability and evaluation. Regular performance reviews and institutional audits should be implemented to ensure that leaders adhere to their mandates and contribute to the institution’s strategic goals. These internal accountability mechanisms are essential for preventing the entrenchment of power and ensuring that leadership appointments remain meritocratic over time (Teferra, 2014).\n\n4.4.2 Legislative and Policy Frameworks\n\nThe Ethiopian government plays a critical role in fostering a meritocratic environment within higher education through the development and enforcement of legal and policy frameworks. A key step is the revision of existing laws and regulations governing university leadership appointments to include meritocratic principles. This would entail formalizing the criteria for leadership roles in national higher education policies, ensuring that all appointments are based on transparent and objective standards (Berhanu & Woldehanna, 2021). Legal frameworks should explicitly prohibit ethnic favoritism and political patronage in leadership appointments, making it mandatory for universities to adhere to meritocratic procedures.\n\nMoreover, the Ministry of Education and other relevant bodies should enforce regulations that ensure compliance with merit-based recruitment and selection processes. Independent oversight bodies could be established to monitor the appointment of university leaders and to investigate potential cases of nepotism, ethnic favoritism, or political interference. These bodies should have the authority to nullify appointments that violate meritocratic principles and recommend corrective actions, ensuring that university leadership is not compromised by external political pressures (Altbach, 2011).\n\n4.4.3 Inclusive Leadership and Representation\n\nWhile meritocracy focuses on individual qualifications, it is equally important to ensure that leadership structures reflect the diversity of Ethiopia’s population. Promoting meritocracy does not mean ignoring the country’s ethnic diversity; instead, strategies must ensure that merit-based governance is compatible with inclusive leadership practices. Universities should strive for a balance between selecting leaders based on merit and ensuring that leadership teams are representative of Ethiopia’s different ethnic groups. This approach can help reduce ethnic tensions by promoting a sense of inclusion while maintaining a focus on competence (Berhanu & Woldehanna, 2021).\n\nOne strategy for achieving this balance is to implement policies that encourage ethnic and gender diversity within leadership teams while maintaining merit-based criteria as the primary basis for appointments. For example, universities could adopt policies that require leadership teams to include individuals from diverse backgrounds, provided that all candidates meet the established qualifications for their roles. Such policies ensure that leadership remains both inclusive and meritocratic, helping to prevent the exclusion of minority groups while promoting excellence in governance (Teshome, 2007).\n\nAdditionally, the promotion of inclusive leadership extends beyond ethnic representation to include gender equity. Ensuring that women are adequately represented in leadership positions is crucial for fostering a more inclusive and diverse academic environment. Gender equity initiatives that support the advancement of women in academic leadership, such as mentorship programs and leadership development workshops, can help address the underrepresentation of women in Ethiopian university leadership roles (Ayenew, 2019).\n\n4.4.4 Depoliticization of Higher Education\n\nOne of the most significant challenges to implementing meritocracy in Ethiopian universities is the deep entrenchment of political influence in the education sector. To promote merit-based governance, it is necessary to depoliticize higher education leadership appointments. This requires a commitment from both the government and universities to limit political interference in the selection and evaluation of leaders. Political appointees often prioritize loyalty to their political patrons over the academic mission of the institution, leading to poor governance and academic decline (Teferra, 2017). Therefore, depoliticizing university leadership is essential for fostering a meritocratic system.\n\nDepoliticization can be achieved by creating independent bodies responsible for overseeing leadership appointments and ensuring that these bodies operate free from political influence. For instance, university senates or independent commissions composed of academic professionals, civil society representatives, and educational experts could be empowered to select university leaders based on objective, merit-based criteria. These bodies must be shielded from political pressures and have the autonomy to make decisions that are in the best interest of the academic institution rather than political parties (Woldemariam, 2018).\n\nAnother important aspect of depoliticization is fostering a culture of academic freedom within Ethiopian universities. By protecting the autonomy of academic institutions, the government can help create an environment where university leaders are free to make decisions based on academic and administrative needs rather than political expediency. This can be achieved through legislation that enshrines the independence of higher education institutions and prohibits political interference in academic affairs (Ashcroft, 2018).\n\n4.4.5 Building a Meritocratic Culture and Political Will\n\nUltimately, the success of any meritocratic system in Ethiopian higher education depends on the development of a meritocratic culture within both universities and society at large. This culture must be built through sustained efforts to promote the values of excellence, integrity, and fairness in leadership appointments. Universities should foster a meritocratic ethos among faculty and staff by encouraging a focus on academic achievement, professional development, and ethical governance (Yigremew, 2016).\n\nPolitical will is also essential for the long-term implementation of meritocracy in Ethiopian higher education. While the government plays a key role in establishing the legal and policy frameworks for merit-based governance, political leaders must also commit to upholding these principles in practice. This requires a departure from the political traditions of patronage and clientelism, which have long shaped leadership appointments in Ethiopian universities. Political leaders must recognize that merit-based governance is in the best interest of national development and higher education reform (Teferra, 2017). Furthermore, civil society, academic organizations, and international partners can play a critical role in advocating for merit-based reforms in Ethiopia’s higher education system. By raising awareness of the benefits of meritocracy and holding both universities and the government accountable for leadership appointments, these groups can help build momentum for meaningful change.\n\nConsistent with the above views, primary data sources confirmed that:\n\nTo move toward a meritocratic system, Ethiopia’s higher education institutions need legal reforms that establish clear guidelines for leadership appointments based on academic and managerial qualifications. The Ministry of Education should create independent oversight bodies to monitor and ensure compliance with merit-based appointment practices. An independent body that oversees leadership appointments could ensure that merit is prioritized over ethnicity. This body should be transparent, and its processes should be open to scrutiny by stakeholders, including students and faculty. Merit-based leaders are more likely to be impartial, fostering a culture of excellence within the university (Interview, Ex-University Leader, Hawassa, 2024).\n\nIn the same vein, Interview with Government Official asserted that:\n\nIt is essential to address the political dimensions of ethnic-based appointments. One strategy could be to depoliticize university leadership by creating selection committees that include representatives from different academic fields, civil society, and external experts. These committees should be insulated from ethnic or political interference (Interview with Government Official, Addis Ababa, 2024).\n\nOn the other hand, Focus Group Discussion results attested that:\n\nPromoting meritocracy also requires changing the organizational culture within universities. There needs to be greater emphasis on performance evaluations, leadership training, and professional development. Leaders who demonstrate strong academic and managerial capabilities should be promoted, regardless of their ethnic background (FGD, Addis Ababa, 2024).\n\nThe findings reveal the multifaceted challenges and opportunities of fostering a merit-based system within a complex socio-political landscape. Grounded in institutional theory, the research identifies how historical practices and cultural norms within Ethiopian universities can serve as significant barriers to the effective implementation of meritocratic principles. By advocating for systemic changes that prioritize qualifications and competencies, the study emphasizes the need for universities to redefine their governance structures and processes to mitigate ethnic favoritism. Principal-agent theory further informs the discussion by illustrating how establishing clear accountability mechanisms can enhance transparency and trust between university leadership and stakeholders, ensuring that leaders are incentivized to prioritize academic excellence over ethnic loyalties. Moreover, meritocratic theory underlines the importance of equitable access to resources and opportunities for all students and faculty, regardless of their ethnic background, to create an environment conducive to academic achievement. By integrating these theoretical perspectives, the findings underscore that a comprehensive strategy for implementing meritocracy in Ethiopia’s higher education system must involve institutional reforms, stakeholder engagement, and a commitment to fostering a culture of excellence that transcends ethnic affiliations, ultimately enhancing the quality and integrity of higher education in the country.\n\n\nConclusion\n\nThis study presents a critical examination of the ethnicization of leadership in Ethiopian higher education and the pressing need for governance reforms that prioritize merit-based appointments. The practice of appointing leaders based on ethnic affiliation, rather than academic qualifications and professional competencies, has its roots in Ethiopia’s historical and political context, particularly the shift towards ethnic federalism following the 1991 political restructuring. While the system of ethnic federalism was introduced to rectify historical grievances and promote ethnic representation, it has inadvertently led to the politicization of university governance, significantly undermining institutional autonomy, academic performance, and the overall quality of higher education in the country.\n\nSince 1991, with the introduction of ethnic federalism in Ethiopia, ethnicized appointments and leadership have increasingly shaped the country’s higher education institutions. Ethnic federalism, designed to give regions greater autonomy, has led to the politicization of federal institutions, reducing them to extensions of regional power rather than truly national entities. As a result, leadership positions in universities have been filled based on ethnic identity rather than merit, compromising the quality, excellence, and innovation in these institutions.\n\nThis system has contributed to a decline in academic standards, diminished institutional performance, and a culture of favoritism, which has enabled the expansion of rampant corruption. Furthermore, ethnicized leadership has hindered effective governance, as leaders are often more accountable to regional or political interests than to the broader goals of academic excellence and national development. The impacts are profound, weakening transparency, reducing innovation, and limiting Ethiopia’s ability to compete globally in higher education.\n\nThe consequences of ethnic-based leadership are far-reaching. As this study reveals, such appointments frequently compromise the integrity of higher education institutions by prioritizing ethnic loyalty over merit. This has resulted in a leadership structure that lacks the necessary qualifications and managerial competence to effectively run universities, leading to inefficiencies in governance, diminished academic standards, and, ultimately, a decline in institutional performance. The erosion of meritocratic principles has also discouraged talented and qualified individuals from taking leadership roles, creating a culture of exclusion where the focus is on ethnic identity rather than on the skills and expertise necessary for institutional growth and innovation.\n\nOne of the most profound findings of this study is that ethnicized leadership undermines the academic mission of Ethiopian universities. Universities, by their nature, are meant to be spaces of critical thinking, innovation, and the pursuit of knowledge, guided by principles of academic freedom and institutional autonomy. However, the politicization of leadership appointments has stifled these values, as leaders selected on the basis of ethnicity are often beholden to political or ethnic allegiances rather than to the academic community they serve. This dynamic hampers decision-making processes, stifles academic freedom, and creates an environment where nepotism and favoritism flourish. As a result, institutional goals are often subordinated to political agendas, diminishing the university’s role as a center of academic excellence and societal progress.\n\nIn contrast, merit-based governance holds significant promise for transforming the governance structures of Ethiopian universities. By emphasizing academic qualifications, managerial skills, and leadership competencies, merit-based systems offer a pathway to restoring the integrity and effectiveness of higher education institutions. As this study highlights, merit-based leadership fosters accountability, transparency, and performance—qualities essential for the development of a robust and competitive higher education system. When university leaders are selected based on their qualifications and experience, they are more likely to prioritize institutional objectives, promote academic freedom, and pursue policies that enhance institutional performance. This, in turn, creates a more conducive environment for learning, research, and innovation, ultimately benefiting students, faculty, and the broader society.\n\nMoreover, adopting a meritocratic approach to university governance is essential for addressing the various inefficiencies currently plaguing Ethiopian higher education. Ethnic-based appointments have led to governance structures that are often opaque and unaccountable, with decisions being made based on political or ethnic considerations rather than on what is best for the institution. Merit-based governance, by contrast, promotes transparency by ensuring that leaders are accountable to the academic community and to the institution’s long-term goals. It also enhances institutional performance by aligning leadership decisions with the needs of students, faculty, and other stakeholders, leading to better resource management, improved academic standards, and more effective governance.\n\nThis study also underscores the importance of institutional reforms, legal frameworks, and inclusive leadership policies in fostering a merit-based governance system. To transition from ethnicized to meritocratic leadership, Ethiopian universities must implement reforms that depoliticize leadership appointments and embed meritocratic principles within the governance structures of higher education institutions. This requires not only revising the legal frameworks governing university appointments but also fostering a culture that values and promotes academic excellence, competence, and leadership based on merit rather than on ethnic or political considerations.\n\nCapacity building is also crucial for ensuring the success of these reforms. Universities must invest in developing the leadership skills and managerial competencies of their staff, ensuring that those in leadership positions have the necessary skills to govern effectively. This includes providing training programs, mentorship opportunities, and other professional development initiatives that prepare academic staff for leadership roles. Additionally, inclusive leadership practices must be promoted to ensure that all members of the academic community, regardless of their ethnic background, have the opportunity to contribute to the governance of their institutions.\n\nDepoliticizing the education sector is another critical step toward fostering meritocratic governance in Ethiopian higher education. As long as political considerations play a central role in leadership appointments, universities will remain vulnerable to the inefficiencies and corruption that arise from ethnicized governance. By insulating higher education institutions from political interference and ensuring that leadership appointments are made based on merit, Ethiopian universities can begin to reclaim their autonomy and fulfill their mission of providing high-quality education and contributing to national development.\n\nWhile the challenges of implementing meritocracy in Ethiopian higher education are significant, the long-term benefits are substantial. A shift towards merit-based governance will not only improve the accountability and transparency of university leadership but will also enhance the overall performance of higher education institutions. This, in turn, will strengthen academic standards, foster innovation, and improve the competitiveness of Ethiopian universities on the global stage. By prioritizing merit over ethnicity, Ethiopian higher education institutions can become more inclusive, equitable, and effective, ultimately contributing to the social and economic development of the country.\n\nThe theoretical framework used in this study—drawing on institutional theory, principal-agent theory, and meritocratic theory—provides a robust foundation for understanding the complexities of leadership in Ethiopian universities. Institutional theory highlights the cultural and historical legacies that have shaped ethnic-based leadership appointments, suggesting that entrenched norms and practices can impede the adoption of merit-based governance. Principal-agent theory emphasizes the need for accountability mechanisms that align the interests of university leaders with those of the institution, fostering a culture of responsibility and transparency. Finally, meritocratic theory underscores the importance of creating an inclusive environment where leadership appointments are based on qualifications and competence, rather than on ethnic identity or political loyalty.\n\nTherefore, this study emphasizes that the quest for de-ethnicizing leadership in Ethiopian higher education is not simply a matter of political correctness, but a fundamental necessity for improving the quality and effectiveness of university governance. Merit-based governance offers a viable solution for addressing the challenges posed by ethnicized leadership, fostering accountability, transparency, and institutional performance. By embracing meritocracy, Ethiopian universities can transform their leadership dynamics, restore academic integrity, and create a more just and effective educational system that serves the needs of all stakeholders. The road to reform may be challenging, but the long-term benefits—strengthened academic standards, enhanced institutional performance, and improved national competitiveness—make it a necessary and worthwhile endeavor.\n\n\nEthics and consent\n\nThe research adhered to stringent ethical standards to protect participants and maintain the integrity of the research process. Written consent was obtained from all participants, who were fully informed about the nature, purpose, and potential risks of the study before agreeing to participate. In this study, informed consent was obtained from all participants. Written consent was secured to ensure that participants fully understood the study’s purpose, procedures, and their rights, including the right to withdraw at any time without consequence. The study adhered to all ethical guidelines as approved by the ethical review committee, and no waiver of consent was granted. If verbal consent had been used, it would have been clearly documented along with the reasons for this approach, and such a procedure would have been explicitly approved by the ethics committee. However, in this study, written consent was used to maintain rigorous ethical standards. This ensured that participants were aware of their rights, including the right to withdraw from the study at any time without consequences (Orb, Eisenhauer, & Wynaden, 2001).\n\nConfidentiality and anonymity were strictly maintained throughout the research process. Identifying information was removed from transcripts, and data was securely stored to prevent unauthorized access. This approach was essential for protecting the privacy of participants and ensuring the ethical conduct of the research (Wiles, 2012). This study received full ethical approval from the Institutional Review Board (IRB) of College of Law and Governance, which comprises five members. The approval was granted on 10/02/2024 with number GaDS-307/2024. All procedures involving human participants were conducted in strict adherence to the Declaration of Helsinki to ensure the ethical integrity of the research.",
"appendix": "Data availability statement\n\nThe Data supporting the findings of this study are subject to restrictions due to confidentiality agreements and privacy considerations. Access to the data is restricted for the following reasons:\n\n• The data include proprietary and confidential information collected under agreements that limit sharing beyond the immediate research team.\n\n• Personal and sensitive information has been anonymized to comply with data protection regulations and to protect the privacy of participants.\n\n• The Institutional Review Board (IRB) of HU/CLG approved the study protocol on 10/02/2024, with approval number GaDS-308/2024. The IRB has stipulated that sharing of the raw data must be done under controlled access to ensure compliance with ethical guidelines and data protection policies.\n\nHow to Apply for Data Access\n\nResearchers, reviewers, or readers interested in accessing the data may submit a formal request to awolali1989@gmail.com. Requests should include the following information:\n\n1. Purpose of Data Access: A clear description of the intended use of the data, including the research objectives.\n\n2. Affiliation: The applicant’s institutional affiliation and contact details.\n\n3. Data Use Agreement: An agreement to comply with the conditions of use, including maintaining data confidentiality and not attempting to re-identify any anonymized information.\n\nRequests will be reviewed on a case-by-case basis to ensure compliance with data protection regulations and ethical considerations. Approved users will be required to sign a Data Use Agreement (DUA) to access the data.\n\n• Data Repository\n\nAll anonymized datasets generated during the study have been archived in the Zenodo repository system and can be accessed at Zenodo Repository. Access to the full raw data is restricted as described above, but the anonymized summary data are available publicly in English.\n\n• For transparency and replication purposes, the following datasets related to the study are available in public repositories:\n\n1. Underlying Data\n\nRepository Name: Zenodo\n\nTitle of Project: Extended Data-2\n\nDOI: https://doi.org/10.5281/zenodo.13863192\n\nCitation: Mohammed, A. A. (2024). Extended Data-2 (New). Zenodo. https://doi.org/10.5281/zenodo.13863192\n\nFile Description: raw\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n2. Extended Data-2\n\nDOI: https://doi.org/10.5281/zenodo.13863192\n\nCitation: Mohammed, A. A. (2024). https://doi.org/10.5281/zenodo.13863192\n\nFile Description: raw\n\nUnderlying Data.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n3. Extended Data\n\nRepository Name: Zenodo\n\nTitle of Project: Extended Data DOI: https://doi.org/10.5281/zenodo.13857205\n\nCitation: [Mohammed, A. A. (2024)]. https://doi.org/10.5281/zenodo.13857205\n\nFile Description: raw\n\nExtended Data.docx\n\nRepository Name: Zenodo\n\nTitle of Project: Supplementary Data\n\nDOI https://doi.org/10.5281/zenodo.13863590\n\nCitation: [Mohammed, A. A. (2024)].\n\nSupplementary Data. Zenodo\n\n75-74-PB.pdf ajol-file-journals_705_articles_267170_65fe6c277d024.pdf\n\ndocument (1).pdf\n\nQuest_for_Transforming_Ethiopian_Higher_Education_.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAalen L: The Politics of Ethnicity in Ethiopia: Actors, Power and Mobilisation under Ethnic Federalism. Brill; 2011. Publisher Full Text\n\nAbbink J: Ethnicity and Conflict Generation in Ethiopia: Some Problems and Prospects of Ethno-Regional Federalism. J. Contemp. Afr. 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Educ. 2019; 14(2): 59–75.\n\nBerhanu K, Woldehanna T: Leadership Challenges in Ethiopia’s Public Universities: The Nexus of Ethnicity, Politics, and Governance. High. Educ. Q. 2021; 75(4): 469–487.\n\nBraun V, Clarke V: Using thematic analysis in psychology. Qual. Res. Psychol. 2006; 3(2): 77–101. Publisher Full Text\n\nCreswell JW, Poth CN: Qualitative inquiry and research design: Choosing among five approaches. 4th ed.Sage Publications; 2018.\n\nGasman M, Abiola U, Travers C: Diversity and senior leadership at elite institutions of higher education. J. Divers. High. Educ. 2015; 8(1): 1–14. Publisher Full Text\n\nJensen MC, Meckling WH: Theory of the firm: Managerial behavior, agency costs, and ownership structure. J. Financ. Econ. 1976; 3(4): 305–360. Publisher Full Text\n\nLeithwood K, Sun J, Schumacker R: How school leadership influences student learning: A test of “The four paths model”. Educ. Adm. Q. 2020; 56(4): 570–599. Publisher Full Text\n\nMahammoda SA: Educational Reforms in Ethiopia: from the Imperial ERA to the Present. Necmettin Erbakan University (Turkey); 2022. Doctoral dissertation.\n\nMarcus HG: A History of Ethiopia. University of California Press; 1994. Publisher Full Text\n\nMerera G: Ethiopia: Competing Ethnic Nationalisms and the Quest for Democracy, 1960-2000. Addis Ababa University Press; 2003.\n\nMeyer JW, Rowan B: Institutionalized organizations: Formal structure as myth and ceremony. Am. J. Sociol. 1977; 83(2): 340–363. Publisher Full Text\n\nMinistry of Education: Higher education policy in Ethiopia: Current reforms. Ethiopian Ministry of Education; 2022.\n\nMinistry of Education: Policy document on merit-based leadership in higher education. Ethiopian Ministry of Education; 2023.\n\nMohammed AA: Extended Data-2. (New), (Zenodo). 2024a. Publisher Full Text\n\nMohammed AA: Extended Data. Zenodo. 2024b. Publisher Full Text\n\nMohammed AA: Supplementary Data. (Zenodo). 2024c. Publisher Full Text\n\nMolla T: Higher education policy reform in Ethiopia: The representation of the problem of gender inequality. High Educ. Pol. 2013; 26: 193–215. Publisher Full Text\n\nMuadin A, Akmalia R: The Quality of Leadership: A Model of Merit-Based Culture in East Borneo. Idarah (Jurnal Pendidikan dan Kependidikan). 2022; 6(2): 185–196. Publisher Full Text\n\nOrb A, Eisenhauer L, Wynaden D: Ethics in qualitative research. J. Nurs. Scholarsh. 2001; 33(1): 93–96. Publisher Full Text\n\nTaye BA, Hailu K: The Practice of Ethnic Federalism in Ethiopia. Imp. J. Interdiscip. Res. 2016.\n\nTeferra D: Governance and Transformations of Higher Education in Africa. Int. J. Afr. High. Educ. 2014; 1(1): 23–39.\n\nTeferra D: African Higher Education: Challenges for the 21st Century. Int. J. High. Educ. Afr. 2017; 5(1): 34–51.\n\nTeferra D, Altbach PG: African higher education: An international reference handbook. Indiana University Press; 2004.\n\nTeshome Y: The Ethiopian Higher Education: Creating Space for Reform. J. High. Educ. Afr. 2007; 5(2-3): 131–157.\n\nValfort M-A: Containing Ethnic Conflicts through Ethical Voting? Evidence from Ethiopia.2007.\n\nVaughan S: Ethnicity and Power in Ethiopia. J. Mod. Afr. Stud. 2003; 41(1): 159–182.\n\nVaughan S, Tronvoll K: The Culture of Power in Contemporary Ethiopian Political Life. Swedish International Development Cooperation Agency (Sida); 2003.\n\nWiles R: What Are Qualitative Research Ethics?Becker ARJA, Lauder MJH, editors. The Ethics of Research with Children: A Handbook of Research Ethics. New York: Routledge; 2012; pp. 69–83.\n\nWoldemariam T: Academic Corruption and Governance in Ethiopian Higher Education: A Case Study of Selected Public Universities. J. Contemp. Afr. Stud. 2018; 36(4): 513–529.\n\nWorld Bank: Ethiopia: Building on progress: A country economic update. World Bank Publications; 2017.\n\nWorld Education News & Reviews: Ethiopian Higher Education: Expansion, Dilemmas and Quality.2011.\n\nYigremew A: The Impact of Corruption on University Governance: Lessons from Ethiopia. Ethiopian Journal of Development Research. 2016; 38(3): 341–356.\n\nYin RK: Case study research and applications: Design and methods. 6th ed.Sage Publications; 2018.\n\nYoung J: Regionalism and Democracy in Ethiopia. Third World Q. 1998; 19(2): 191–204. Publisher Full Text\n\nYoung M: The rise of the meritocracy. Routledge; 2017."
}
|
[
{
"id": "341270",
"date": "14 Dec 2024",
"name": "Ahmad Juhaidi",
"expertise": [
"Reviewer Expertise Educational management",
"educational marketing"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction The authors have clearly outlined the research objectives. However, I recommend that the authors provide more context (higher education in Ethiopian), ethnic issue, and discuss the state-of-the-art developments related to the research topic. Additionally, the authors should emphasize the research gap more explicitly to highlight the significance of their study. To enhance readability, I suggest numbering the research objectives (e.g., RO1, RO2). Literature Review The authors have addressed the research topic within the theoretical framework section. To improve the manuscript’s quality, I recommend including additional relevant literature, particularly focusing on higher education in Ethiopia. This discussion should be supported by citations from credible sources to enrich the context and depth of the analysis. Method In the methodology section, the authors have described sampling techniques and interviews as data collection methods. To enhance trustworthiness and replicability/reproducibility, I recommend the following improvements:\nSpecify the universities included in the study and provide the number of interviewees. Include a table of informants with anonymized codes (e.g., no names), age, gender, and a brief profile. If confidentiality was required, explain who requested the anonymity and why. Elaborate on the measures taken to enhance the trustworthiness of the data. Justify the minimum sample size and explain how the sample size was determined. Specify the timeline of the focus group discussions (FGDs). Include a flowchart or diagram illustrating the data processing procedure, please improve Juhaidi A, et al., 2024 (Ref 1)\nResults and Discussion The authors have included citations from interviews and FGDs in the results section. To further improve the manuscript, I recommend the following:\nAdd more direct quotes from interviews to enrich the qualitative insights. To aid the reader’s comprehension, present the findings visually, such as through charts or diagrams.\nDiscussion The authors have supported their discussion with literature references. To strengthen the analytical depth, I suggest incorporating additional literature and comparisons with studies from other countries. Moreover, I recommend adding a section on theoretical and practical implications to highlight the study's contributions.\nLimitations and Future Research I suggest including a dedicated section on the limitations of the study and directions for future research before the conclusion.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1359
|
https://f1000research.com/articles/13-1358/v1
|
13 Nov 24
|
{
"type": "Study Protocol",
"title": "Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol",
"authors": [
"Jiaying Zhou",
"Mayue Shi",
"Mingzhu Cai",
"Jiaying Zhou"
],
"abstract": "Background Traditional dietary assessments are often inaccurate and prone to self-reporting biases. Tracking the physiological responses associated with eating and digestion events via wearable technologies may provide an effective approach for continuously monitoring food intake and estimating energy consumption. Eating and digestion are accompanied by a series of changes in the heart rate, skin temperature, blood oxygen saturation, and blood pressure. These changes can be tracked by wearable devices, such as smartwatches, which have been widely accepted in the market. This systematic review is the first to evaluate the effectiveness of tracking such physiological biomarkers in differentiating between high- and low-calorie meals, potentially paving the way for more accurate dietary monitoring.\n\nMethods Following the PRISMA-P guidelines, we will conduct a systematic literature search through MEDLINE, EMBASE, and PubMed for clinical trials that investigated physiological responses following meal intake in healthy subjects. Two independent reviewers will screen and select articles based on pre-defined eligibility criteria, with a third review to resolve any discrepancies. This will be followed by data extraction and quality assessment of the included studies. Statistical analyses, including meta-analyses, will be performed using R Studio software. Our primary outcome will be the comparison of physiological biomarkers before and after meal intake, while secondary outcomes will include comparisons of physiological biomarkers between high- and low-calorie meal consumption and the correlation between the caloric content of consumed meals and postprandial physiological changes.\n\nDiscussion This systematic review and meta-analysis will identify physiological indicators for eating events and inform the design of wearable sensors that estimate food intake in healthy subjects.\n\nSystematic Review Registration PROSPERO Registration ID: CRD42024544353",
"keywords": [
"Dietary behaviour",
"food intake",
"physiological biomarkers",
"heart rate",
"blood pressure wearable sensor"
],
"content": "Background\n\nDiet is essential for human health, and understanding what people eat in their daily lives is a fundamental challenge. Traditional dietary assessments rely on self-reporting and present high levels of subjectivity and recall biases. These limitations have driven the development of objective and reliable tools for dietary monitoring.\n\nRecent advances in metabolomic techniques, combined with bioinformatics analysis, have opened new avenues for developing dietary biomarkers. These approaches aim to identify blood or urine metabolites as biomarkers of food intake (BFIs) that reflect the consumption of specific foods or dietary patterns (Cuparencu et al., 2024; Maruvada et al., 2020). However, this approach is limited by laboratory analysis and does not enable continuous dietary monitoring.\n\nWearable sensor-based methods have also been proposed for continuous dietary monitoring. Various wearable sensors function by tracking the oral phase of digestion (capturing bites, chewing, and swallowing actions) and hand gestures to identify eating episodes (Burrows & Rollo, 2019). However, they often fall short of providing contextual meal information, such as energy intake estimates (Vu et al., 2017). Camera-based systems have also been proposed, with the ability to estimate meal energy by measuring food volume and categorizing food types. However, these systems have significant privacy concerns, particularly when personal images are involved (Doulah et al., 2022). To date, a widely accessible, user-friendly tool for real-time monitoring of food and energy intake is still lacking.\n\nTracking the physiological responses associated with eating and digestion events via wearable technologies may provide a solution for the continuous monitoring of food intake. Physiological changes after food consumption, such as increased heart rate, elevated skin temperature, and decreased blood oxygen saturation, have been well documented (De Aguiar Cassiani et al., 2011; Sit & Chou, 1984; Westerterp, 2004). Heart rate changes showed a strong correlation with meal size, suggesting that physiological responses could serve as valuable indicators of both food consumption and energy intake (Sidery & Macdonald, 1994). Despite this, there remains no consensus on whether monitoring physiological responses can serve as reliable indicators of energy intake.\n\nThis systematic review aims to identify and evaluate physiological biomarkers associated with food and energy intake. The specific objectives are: (1) to investigate physiological responses, such as heart rate, blood pressure, skin temperature, and blood oxygen saturation, following the consumption of high-caloric versus low-calorie meals through meta-analysis; and (2) to assess whether there is a dose-response relationship between these physiological changes and the caloric content of meals using meta-regression analysis. This can inform the design of new dietary monitoring tools and whether tracking such changes can effectively differentiate between high- and low-calorie intake.\n\n\nMethods\n\nThis protocol will follow the PRISMA-P Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines to ensure a systematic and transparent process (Moher et al., 2015; Shamseer et al., 2015).\n\nPrimary outcomes:\n\n• Key physiological biomarker fluctuations associated with dietary events, focusing on comparisons between pre- and post-meal periods and between high- and low-calorie meals.\n\nSecondary outcomes:\n\n• Correlation or dose-response relationship between the energy content of consumed meals and subsequent changes in physiological biomarkers.\n\n• Insights into the capabilities and effectiveness of current wearable sensing technologies for tracking dietary intake through physiological biomarkers.\n\nThe eligibility criteria for this review are structured according to the PICO framework to clearly define the target population, interventions, comparators, outcomes, and study context. This framework is essential for identifying physiological biomarkers that reflect dietary behaviors and evaluating their applications in wearable sensing technology for food intake monitoring.\n\nInclusion criteria:\n\n• Healthy participants included individuals who are underweight, overweight, or of normal weight, provided that they are otherwise in good health.\n\nExclusion criteria:\n\n• Patients diagnosed with diabetes, cardiovascular disease, or any other type of chronic condition.\n\n• Animal studies.\n\nInclusion criteria:\n\n• Meal intake with adequate nutrient and calorie information, regardless of meal form (liquid, solid, or mixed)\n\n• Monitoring physiological biomarkers before and after dietary intake. Key physiological biomarkers included heart rate, body temperature, oxygen consumption, cardiac output, blood pressure, blood flow, and blood glucose through a continuous glucose monitor.\n\nExclusion criteria:\n\n• Studies investigating the impacts of water consumption, drug effects, long-term dietary consequences, and specific types of food or exercise\n\n• Studies lacking sufficient information to calculate the test meal’s caloric content\n\nInclusion criteria:\n\n• Comparing the pre- and postprandial changes in physiological biomarkers.\n\n• Comparing the physiological biomarkers changes after consuming meals of different calories content.\n\n• Comparing wearable sensors with traditional methods for monitoring physiological biomarkers related to food intake.\n\nInclusion criteria:\n\n• Pre- and post-meal monitoring of heart rate, skin temperature, blood oxygen saturation, cardiac output, blood pressure, and intestinal blood flow measured using wearable or traditional devices.\n\n• Pre- and post-meal blood glucose monitoring using wearable devices, such as continuous glucose monitors (CGMs).\n\n• If measured using wearable devices, the performance metrics include accuracy, specificity, precision, recall, and F1-score.\n\nExclusion criteria:\n\n• Articles without reported results from empirical research.\n\nStudies involving human participants across various designs will be included, excluding those without human involvement or those focusing solely on sensor algorithms and technical details. The required studies can be conducted in diverse settings, from controlled labs to real-life environments, and must be published in peer-reviewed journals. Exclusions will apply to review articles, commentaries, protocols, and studies lacking empirical results, with a publication cutoff of February 7, 2024. Only articles published in English were included.\n\nInclusion criteria:\n\n• Experiential studies involving human participants in either controlled or real-life environments.\n\n• Randomised or non-randomised trial, including single-arm studies.\n\n• English-language articles in peer-reviewed journals.\n\nExclusion criteria:\n\n• Review articles, commentaries, and protocols.\n\n• Studies without human involvement.\n\nLiterature searches will be conducted across the MEDLINE, EMBASE, and PubMed databases following pre-defined eligibility criteria. We will use search strategies that incorporate both Medical Subject Headings (MeSH) and a suite of keywords pertinent to wearable sensors and their applications in monitoring eating behaviors. The selection of keywords will include terms such as ‘eating,’ ‘energy intake,’ ‘caloric intake,’ ‘postprandial period,’ ‘postprandial state,’ ‘oxygen consumption,’ ‘heart rate,’ ‘blood pressure,’ ‘cardiac output,’ ‘body temperature,’ ‘regional blood flow,’ and ‘blood glucose’ to ensure broad yet relevant coverage. For detailed insights into the search strategy employed for each database, please refer to Supplementary Table 1 (Appendix).\n\nThe literature search results will be uploaded to Covidence, a web-based tool for systematic review and management. The duplicates will be automatically removed upon uploading. Our team will create and refine screening questions and forms, aligning them with predetermined inclusion and exclusion criteria.\n\nThe selection process will start with all three authors independently reviewing the titles and abstracts to check if they met the inclusion criteria. Titles that seem to fit these criteria or whose eligibility is not clear will be selected for a full-report review to confirm that they comply with the inclusion criteria. Conflicts on Covidence will be resolved through discussions in review team meetings, and the reasons for excluding texts will be recorded. The flow diagram of the article selection process for Covidence will be shown in the PRISMA flow diagram Supplementary Figure 1.\n\nSupplementary Figure 1 (Refer extended data) PRISMA Flow Diagram of the Article Screening Process.\n\nJ.Z. will independently extract specified characteristics from selected studies into a designated Excel spreadsheet for data extraction. Subsequently, M.C. and M.S. will independently assessed the extracted data. Any discrepancies identified during the review will b resolved through team meetings. Given the diversity of the data items to be extracted and the varied focus across papers, it is expected that not all papers will contain every piece of desired information.\n\nPre-defined characteristics from the selected eligible studies will be extracted into a data extraction Excel spreadsheet. The information set for extraction will include the following:\n\nStudy design: randomised trials or non-randomised studies.\n\nPopulation:\n\n1. Participant characteristics including age, gender, BMI, ethnicity, and healthy status.\n\n2. Sample size: number of participants enrolled and analysed in the study.\n\nIntervention:\n\n3. Meal content: Food items, nutritional, and calorie information. Calorie intake will be either extracted directly or calculated using reported nutritional information.\n\n4. Timing and length of meal consumption\n\n5. Fasting duration before interventions\n\nComparisons:\n\n6. Definition of ‘control’ groups (e.g., pre-meal vs. post-meal; high-calorie vs. low-calorie meal)\n\nOutcomes:\n\n7. Quantitative data on physiological biomarkers: Time-series changes in heart rate, skin temperature, blood oxygen saturation, cardiac output, blood pressure, and intestinal blood flow before and after meals\n\n8. Measurement instrument and intervals: Indicate whether outcomes are measured using traditional or wearable devices. If wearable devices are used, the performance metrics (e.g., accuracy, specificity, precision, recall, and F1-score) of the wearable sensors will be extracted, where applicable.\n\nIn this systematic review, a comprehensive assessment of the risk of bias in individual studies will b conducted to ensure the reliability and validity of our findings. We will follow the structured guidelines provided in Chapter 25 of the Cochrane Handbook for Systematic Reviews of Interventions, utilizing specific tools tailored to the type of study under review (Higgins et al., 2019).\n\n• Risk of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized studies, evaluating domains such as confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results (Sterne, Jonathan AC et al., 2016).\n\n• Risk of Bias (RoB) 2 tool for randomized studies, examining domains including the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results (Sterne, Jonathan A. C. et al., 2019).\n\nRisk of bias assessment will be carried out at both the study and outcome levels to identify biases that could impact the overall study or specific outcomes. The results of these assessments will b crucial to the data synthesis process.\n\n• Categorization of Studies: Each study will be categorized based on its assessed risk of bias: low, moderate, high, or critical. This categorization directly influenced the weight of each study contributing to the synthesis.\n\n• Interpretation of Findings: Categorization will also play a vital role in interpreting the review’s findings, especially when integrating results from studies with high or critical risk of bias.\n\nThe results of the risk of bias assessments will be visualized using Robvis, a tool that generates high-quality publication-ready figures summarizing these assessments for systematic reviews (McGuinness & Higgins, 2021). This visualization tool allows for customization according to the specific assessment tools used, such as RoB 2 or ROBINS-I, ensuring that our review’s risk-of-bias visualization is both informative and tailored to our specific methodology. These visualizations will aid in transparent reporting and a detailed discussion of the biases inherent in the included studies.\n\nThis systematic review willintegrates quantitative data from studies that examine physiological changes in postprandial status. Given the anticipated variation in study designs, populations, and measurement methods, we will initially perform a narrative synthesis to summarize and interpret the findings across different studies.\n\nA meta-analysis will be considered if the data extracted from the included studies demonstrate sufficient homogeneity in terms of the study design, intervention types, and reported outcomes. Our meta-analytic process willinclude the following steps.\n\n1. Software for Data Synthesis: Statistical analyses, including meta-analysis, will be conducted using R Studio with the ‘metafor’ package, supporting fixed and random-effects models, heterogeneity assessment, subgroup, and sensitivity analyses.\n\n2. Models for Meta-Analysis: We will select the meta-analytic model based on the data characteristics; a fixed-effects model will be used if the studies are sufficiently similar. Otherwise, a random-effects model will be employed to account for variability both within and across studies, if significant heterogeneity was detected.\n\n3. Heterogeneity and Sensitivity Analysis: Heterogeneity will be assessed using the Q test and quantified using the I2 statistic, which indicates the proportion of variance due to actual differences rather than chance, with values over 50% indicating substantial heterogeneity. Sensitivity analyses will be conducted by systematically excluding each study to check for significant changes in heterogeneity and overall results, ensuring that no single study disproportionately influences the effect sizes.\n\n4. Subgroup Analyses and Meta-Regression: Subgroup analyses will be conducted to investigate whether moderators, such as high- and low-calorie meals, influence physiological biomarker changes differently. Meta-regression was performed to assess whether a dose-response relationship exists.\n\n5. Assessment of Reporting Biases: To investigate potential publication biases, funnel plots will be used for visual examination and Egger’s test will be used to statistically determine the likelihood of bias influencing the reported results.\n\nWhere caloric information is missing, it will be calculated based on the macronutrient composition of the meal. Alternatively, the authors of the original study will be contacted.\n\nWhere necessary, we will calculate standard deviations from the provided sample size and standard error mean or consider estimation methods if original data cannot be retrieved, adhering to the Cochrane guidelines (Higgins et al., 2019).\n\nWe used the GRADE framework to assess the quality of the evidence. Adjustments to the quality ratings will be made based on several factors: (i) Risk of Bias (RoB) across studies, (ii) indirect evidence, (iii) inconsistency of results, (iv) imprecision in data, and (v) Potential for Publication Bias. Evidence levels will be categorized as “high”, “moderate”, or “low”. Each reason for potential downgrade will be evaluated as “none,” “serious,” or “very serious.”\n\n\nDiscussion\n\nWearable devices have shown promise for monitoring eating episodes by capturing eating gestures or food images. Integrating physiological parameters, such as heart rate, blood pressure, and skin temperature, may enhance the estimation of food and energy intake. A systematic review is needed to consolidate the current evidence on the relationship between these physiological parameters and dietary intake and to assess the potential for tracking these changes in differentiating high- and low-calorie intake.\n\nThis protocol is designed in strict adherence to the PRISMA-P guidelines to ensure the execution of a high-quality systematic review and meta-analysis. To our knowledge, this review is the first to systematically investigate the changes in key physiological biomarkers from pre- to post-meal states and their relationships with energy intake. The planned systematic review will enhance our understanding of physiological responses following dietary intake and may inform new wearable technologies for more accurate and real-time monitoring of food consumption.\n\n\nDeclarations\n\nThis systematic review does not require ethical approval as it relies on previously published studies that contain non-identifiable data. The outcomes of the review will be shared through publication in a peer-reviewed journal, and presentations at conferences and seminars.\n\n\nPatient consent for publication\n\nNot required.\n\n\nAuthor’s contributions\n\nM.C. and M.S. designed and directed the project; M.C. and M.S. acquired funding as co-PIs; J.Z., M.C., and M.S. wrote this protocol.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: Extended data for ‘Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol’. DOI: https://doi.org/10.6084/m9.figshare.27303741.v1 (Zhou et al., 2024).\n\nThe project contains the following extended data:\n\n• Data file 2: Search Strategy\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Extended data for ‘Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol’. DOI: https://doi.org/10.6084/m9.figshare.27303741.v1 (Zhou et al., 2024).\n\nThe project contains the following Reporting guidelines:\n\n• Data file 1: PRISMA Flow Chart\n\n• Data file 3: PRISMA-P Checklist\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nBurrows TL, Rollo ME: Advancement in Dietary Assessment and Self-Monitoring Using Technology. Nutrients. 2019; 11(7): 1648. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCuparencu C, Bulmuş-Tüccar T, Stanstrup J, et al.: Towards nutrition with precision: unlocking biomarkers as dietary assessment tools. Nat. Metab. 2024; 6(8): 1438–1453. PubMed Abstract | Publisher Full Text\n\nDe Aguiar Cassiani R, Manfredi C, Santos JA, et al.: Arterial oxygen saturation and heart rate during a meal in chronic obstructive pulmonary disease.2011.\n\nDoulah A, Ghosh T, Hossain D, et al.: Energy intake estimation using a novel wearable sensor and food images in a laboratory (pseudo-free-living) meal setting: quantification and contribution of sources of error. Springer Science and Business Media LLC; 2022.\n\nHiggins JPT, Thomas J, Chandler J, et al.: Cochrane Handbook for Systematic Reviews of Interventions. Wiley Cochrane Series. 2nd ed.Newark: John Wiley & Sons, Ltd; 2019.\n\nMaruvada P, Lampe JW, Wishart DS, et al.: Perspective: Dietary Biomarkers of Intake and Exposure—Exploration with Omics Approaches. Adv. Nutr. 2020; 11(2): 200–215. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcGuinness LA, Higgins JPT: Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res. Synth. Methods. 2021; 12(1): 55–61. PubMed Abstract | Publisher Full Text\n\nMoher D, Shamseer L, Clarke M, et al.: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015; 4(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nShamseer L, Moher D, Clarke M, et al.: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 349(jan02 1): 7647. PubMed Abstract | Publisher Full Text\n\nSidery MB, Macdonald IA: The effect of meal size on the cardiovascular responses to food ingestion. Br. J. Nutr. 1994; 71(6): 835–848. PubMed Abstract | Publisher Full Text\n\nSit SP, Chou CC: Time course of jejunal blood flow, O2 uptake, and O2 extraction during nutrient absorption. Am. J. Physiol. Heart Circ. Physiol. 1984; 247(3): H395–H402. PubMed Abstract | Publisher Full Text\n\nSterne JAC, Savović J, Page MJ, et al.: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Online). 2019; 366: l4898. Publisher Full Text\n\nSterne JA, Hernán MA, Reeves BC, et al.: ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ (Online). 2016; 355: i4919. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVu T, Lin F, Alshurafa N, et al.: Wearable Food Intake Monitoring Technologies: A Comprehensive Review. Computers (Basel). 2017; 6(1): 4. Publisher Full Text\n\nWesterterp KR: Diet induced thermogenesis. Nutr. Metab. 2004; 1(1): 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhou J, Shi M, Cai M: Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "343907",
"date": "27 Jan 2025",
"name": "Faiza Jan Iftikhar",
"expertise": [
"Reviewer Expertise Bio sensor /chemical sensors including wearable sensor."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work is innovative but does not touch the theme of oncology or related research as is the focus of the journal. It aims to assess the effectiveness of wearable technologies by tracking physiological biomarkers pre- and postprandial. It is contended that the wearable devices are able to monitor the changes in heart rate, oxygen level, skin temperature etc., in a more accurate and continuous manner. This study aims to study these biomarkers that results due to high and low calories meals.\n\nIt should be made clear that it is a secondary research. The PICO method is not explained and the different PICOs are given though with some repetition Different frameworks are being referred to but not explained. The expected results of the methods used is not given. Hence outcomes are not clear. They should include measurable results expected from the test It looks more like writing a review but expected results and findings extracted from secondary research is not given It says: Comparing wearable sensors with traditional methods for monitoring physiological biomarkers related to food intake. Mention what are the traditional methods that will be compared with.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1358
|
https://f1000research.com/articles/12-1226/v1
|
27 Sep 23
|
{
"type": "Systematic Review",
"title": "Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review",
"authors": [
"William Tendi",
"Putu Angga Risky Raharja",
"Irfan Wahyudi",
"Arry Rodjani",
"Gerhard Reinaldi Situmorang",
"William Tendi",
"Putu Angga Risky Raharja",
"Irfan Wahyudi",
"Arry Rodjani"
],
"abstract": "Background: Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. On the other hand, in post-pubertal UDT, the current guideline recommends orchiectomy; however, this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods: A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results: Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions: The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility.",
"keywords": [
"Orchidopexy",
"Orchiectomy",
"Testicular malignancy",
"Undescended testes"
],
"content": "Introduction\n\nUndescended testes (UDT), or cryptorchidism, is the absence of one or both testes in the scrotum.1 Internationally, the incidence of this condition was 1.0–4.6% of full-term and 1.1–45% of preterm neonates. However, most UDT patients have spontaneous descent in which the prevalence range is between 1–1.5% at the age of three months, 1–2.5% at nine months, and only 1% of all full-term infants still had UDT after reaching one year of age.1,2\n\nGenerally, UDT is classified into palpable and non-palpable, and in most cases, the testis is palpable (80%). The location of the testes is usually within the tract of normal testicular descent, which is the inguinal canal, or far above (intraabdominal). However, it is also possible for the testis to be placed outside the tract (ectopic testis) or not to be present at all, as in the case of agenesis and vanishing testis. Among these types and locations, about 50–60% of non-palpable testis is intraabdominal.2\n\nRegarding the treatment of UDT, the choices of therapy vary between medical management using hormonal therapy and surgical intervention, such as orchidopexy. The current guidelines advise that treatment should start at the age of six months and be finished by 12–18 months to prevent any loss of germ cells and Leydig cells.2 In addition, an early orchidopexy performed before puberty could reduce the risk of testicular germ cell tumour.3\n\nWhen UDT is not detected or corrected before the patient reaches puberty, there are specific guidelines regarding post-pubertal UDT. The European Association of Urology (EAU) guidelines recommend discussing orchiectomy in such cases with patients. However, this recommendation is weak and seems insufficient.4 Moreover, there is still a possibility of improving the fertility of patients with post-pubertal UDT. Recently, a systematic review conducted by Muncey et al.5 revealed that patients with uncorrected bilateral inguinal UDT retain the possibility of fertility after undergoing a post-pubertal orchidopexy. Therefore, adult patients with uncorrected UDT might reconsider orchidopexy instead of orchiectomy. In addition, to the best of the authors’ knowledge, there is no high-level evidence, such as systematic reviews or meta-analyses, regarding the management of post-pubertal UDT from the malignancy risk point of view so far. This study aimed to systematically review the available literature to provide valid recommendations for post-pubertal UDT management, with a focus on the risk of malignancy.\n\n\nMethods\n\nThis study focused on the best option to treat UDT if the condition was not corrected at the age of puberty. Therefore, the population included in this study was male adolescents or adults with a history of UDT who were treated after puberty. If the pubertal status was not explicitly mentioned, the cut-off pubertal age used in this study was 12 years or older, based on an average pubertal age in boys of 11.5 years old.6 The diagnosis of UDT included in this study can either be unilateral or bilateral.\n\nThe intervention in this study was orchiectomy, which was compared with orchidopexy. There were no limitations regarding the surgical technique or the approach used in either procedure. In addition, the primary outcome of this study was the occurrence of any testicular malignancy identified after the intervention was performed.\n\nA comprehensive and systematic literature search was performed on 5 March 2023 in PubMed, Wiley Online Library, and Cochrane Library. The keywords used were “UDT”, “undescended testis”, “undescended testes”, “cryptorchidism”, “orchidectomy”, “orchiectomy”, “testicular removal”, “testes removal”, “testis removal”, “orchidopexy”, “orchiopexy”, “fowler-stephens”, “testicular cancer” and “testicular malignancy”. The study design was either case report, case series, clinical trials or observational studies, such as cohort and case-control. There was no publication time or country restriction. The inclusion criteria in this review were any studies of patients who had a history of UDT and had reached puberty when the orchiectomy or orchidopexy was performed, with a report regarding whether testicular malignancy of any type developed after the surgery, in which there was no limitation in the follow-up time. Studies not written in English were included, as long as the abstract was in English and provided the data needed in this review. The exclusion criteria were studies that did not specify the timing of UDT intervention, had no history of UDT correction at the time of malignancy diagnosis and did not have the full text available online.\n\nAll search results were screened for duplicates and relevancy by all authors. After the inclusion and exclusion criteria were applied, the articles included were independently appraised by two reviewers (WT and GRS) and any disagreement was settled by consensus and decided by the third reviewer (PARR). All the searching and screening processes were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart7. The risk of bias assessment and appraisal were performed using the Newcastle–Ottawa scale for cohort and case-control studies.8 The cross-sectional studies and case reports were appraised using the Joanna Briggs Institute (JBI) tool.9 Low quality evidence was determined by a Jadad score of less than three, Newcastle-Ottawa score of less than five, and JBI score of less than 50% (excluded).\n\nThe data collected in this review were the UDT status of the patients (unilateral/bilateral), location of the UDT, age of the patients when the intervention was performed, type of treatment (orchiectomy/orchidopexy), follow-up time, presence of testicular malignancy, type of testicular malignancy and presence of metastasis. Among these variables, the outcome was the occurrence of testicular malignancy. The data extraction, bias and quality assessment were performed by two authors (WT and GRS) and any disagreement was resolved with the third author (PARR). The data extraction, including the assessment of heterogeneity and bias was performed manually and the result was then presented as a table in which all the variables were summarized.\n\n\nResults\n\nThere were initially 150 articles identified, of which there were two duplicates. After screening them for relevancy and applying the inclusion and exclusion criteria, seven studies were included and reviewed (Figure 1).\n\nThe risk of bias assessment and appraisal for the seven articles showed that there were three good quality cohort and case-control studies (with a score of 6 for each article), one cross-sectional study and three case reports. All articles presented post-pubertal patient(s) with either unilateral or bilateral UDT and orchidopexy or orchidectomy was performed on the patient(s) with most of the studies observed developed testicular malignancies on later investigation (ranged between 0–252 months after procedure). A summary of the studies’ quality assessment is presented in Table 1. Overall, 42 patients with UDT underwent post-pubertal correction, either by orchidopexy or orchiectomy, which is shown in Table 2. The age of the patients during UDT correction ranged between 13–34 years old and the location of the testes was mostly at inguinal level of intraabdominal. Only one article (Jacobellis et al.16) did not report the location of the testes and Lopes et al. showed an unusual report of bilateral ectopic testes at the right external inguinal ring and below the spleen.15 In addition, the type of testicular malignancy found in these studies were seminoma, teratoma, carcinoma in situ of the testis, and adenocarcinoma of rete testis. Nevertheless, there was heterogeneity of the outcomes between studies. Torricelli et al. found there was no malignancy occurred among the observed 14 patients, and Ford et al. reported only one out of 13 post-pubertal unilateral UDT patients corrected with orchidopexy developed malignancy (7.6%).10,11 However, Wobb et al. observed 100% of the patients (3 of 3) had testicular malignancy.13 The heterogeneity might be caused by few numbers of patients observed in both studies. In addition, the mean follow-up time of Torricelli et al. was only 48.7 months, and Ford et al. did not mention how long the follow-up time was. On the other hand, Wobb et al. observed the patients for a mean time of 112 months. Hence, it is possible that the follow-up time might not be long enough for both authors to find proof of testicular malignancy for the other patients.\n\nDespite the good quality score of the articles included, there were reporting bias of the observational studies, which might contribute to the heterogeneity of the results. The lack of reported follow-up time was also observed in the study conducted by Pike et al. Moreover, the authors also did not report specifically how many testicular malignancies occurred among the nine patients observed. Another reporting bias found from most of the observational studies included in this review is the lack of information regarding the specific number of unilateral or bilateral UDT among all the patients. However, the information extracted from the studies included was sufficient to be reviewed to assess the occurrence of testicular malignancy in post-pubertal corrected UDT patients.\n\n\nDiscussion\n\nThe current review showed that most of the patients with post-pubertal UDT had the testes located inguinally or intraabdominally. Only one case from Lopes et al. reported a UDT in which the left testis was located just below the spleen. In this unique case, a 36-year-old male presented with infertility and bilateral UDT. The histopathological examination revealed that he had carcinoma in situ with splenogonadal fusion in the left testis and no trace of malignancy in his right testis. The patient then underwent a right orchidopexy and a left orchiectomy with the insertion of a testicular prosthesis.15\n\nRegarding the UDT treatment options, the most common post-pubertal procedure performed in this study was orchidopexy. The study by Wobbes et al. revealed that all three patients who underwent an orchidopexy after puberty developed a testicular tumour in 112 months (mean time range) after orchidopexy, regardless of whether the UDT was unilateral or bilateral. The histopathological examination showed seminoma and embryonal carcinoma in two patients with right unilateral UDT and teratoma/seminoma in the left testis of a bilateral UDT patient who underwent bilateral orchidopexy. Interestingly, the study also observed that nine other patients underwent orchidopexy just before puberty and all developed testicular malignancy in 12–29 years after intervention. This fact suggests that late orchidopexy, both before and after puberty, might not reduce the malignancy risk well.13\n\nHowever, one article revealed that no malignancy occurred in patients who underwent post-pubertal intervention. Torricelli et al. assessed 14 unilateral and bilateral UDT patients with a mean age of 29 years (18–54 years) when the UDT was corrected with either orchidopexy or orchiectomy. All of the testes were located intraabdominally, and the orchiectomies were performed due to either the small size or difficulty in dissection. The mean follow-up time was 48.7 months, and there was no malignancy found in any of the patients, despite the higher chance of carcinoma in situ in intraabdominal UDT. This suggests the same level of efficacy of both orchidopexy and orchiectomy in a post-pubertal setting.3,10 Nevertheless, it should also be noted that the follow-up time was the shortest among the reported times in this review.\n\nIn addition, a study by Ford et al. showed that of all 13 unilateral and bilateral UDT patients who had their testes located either inguinally or intraabdominally and underwent post-pubertal orchidopexy, only one developed carcinoma in situ. This suggests that orchidopexy might still be a valid choice in treating post-pubertal UDT. The tumour occurred on the contralateral normal descended testis of one of the unilateral UDT patients.11\n\nPike et al. observed that nine patients with unilateral and bilateral UDT underwent either orchidopexy or orchiectomy at the age of 15–34 years. The study revealed that there was still a chance of testicular malignancy after correction. However, the authors stated that the age distribution of UDT correction, both pre- and post-pubertal, was the same as the expected rate of the national population, suggesting that there was no association between the time of correction and the risk of testicular malignancy. Unfortunately, the study did not specifically mention which treatment group developed malignancy.12\n\nAs mentioned above, a recent systematic review showed that there was a possibility of fertility in men with UDT after orchidopexy, even at an age as late as 38 years old. The parameters used in determining fertility status were sperm count and the evaluation of hormones, including testosterone. However, the authors of that study also mentioned that in bilateral UDT cases in which the testes were located intraabdominally, germ cells were not found.5 A possible explanation of this phenomenon was the non-ideal temperature of the testes for the germ cells to grow.3\n\nA similar result was presented by Rohayem et al. The study stated that despite the inverse correlation among the age of UDT correction, testicular volume and sperm concentration, there were patients who had a late correction and still had normozoospermia and normal serum testosterone while some who had an early correction had azoospermia. Therefore, the chance of UDT patients having a biological child is not lost, even when the condition was neglected after puberty.17\n\nOn the other hand, the risk of testicular germ cell tumours increased five- to 10-fold in patients with UDT compared with the general population and even more so when the UDT was not corrected until puberty and thus post-pubertal orchiectomy was recommended.3,18 However, a recent study by Xu et al. suggested that the recommendation of orchiectomy might depend on the location of the UDT in which orchiectomy or testicular biopsy for malignancy screening in older boys or adolescents should be considered in intraabdominal UDT, whereas inguinal UDT did not mandate the need of testicular biopsy at the time of orchidopexy. In this study, a total of 71 patients aged 10.1–27.7 years old were included and two of the patients developed testicular malignancy (age 16.2 and 26.6 years old). Both patients had intraabdominal UDT and underwent unilateral orchiectomy in which the histopathological finding revealed seminomas.19 The most recent report in January 2023 was published by Faruk et al., in which the authors found a right testicular seminoma in a 24-year-old man with uncorrected bilateral UDT. In the study, the patient underwent right orchiectomy and left orchidopexy followed by close monitoring every four months for the first year, every six months for the second year and then annually for the third to fifth years.14\n\nIn addition, a mortality risk analysis of post-pubertal UDT was published recently by Shah et al. The study balanced the risks of perioperative mortality (POM) and death from germ cell tumours based on age group when the UDT was diagnosed. The POM was defined based on the criteria determined by the American Society of Anesthesiologists (ASA). The result of this study was that prophylactic orchiectomy should only be considered when the patients’ age was below 50 years and healthy (ASA class 1). However, if the patients had mild systemic diseases (ASA class 2), the procedure could be considered when the patients’ age was below 35 years. Patients with ASA class 3 or above should always undergo observation.20 Based on these studies, we propose an algorithm regarding the recommendation of post-pubertal UDT management (Figure 2).\n\nUDT=undescended testes.\n\nAfter either an orchiectomy or orchidopexy, patients should be advised to routinely perform a self-examination, especially those with unilateral correction. In unilateral UDT, there was a slight increase in the risk of malignancy of the contralateral testis.3 A case of contralateral testicular malignancy in unilateral UDT was described by Ueda et al. in 1995. The study showed the case of a 36-year-old man who had left unilateral UDT and presented with painless swelling of his right scrotum. Further examination revealed a seminoma on the right testis, which was then removed. The left testis was found in the left inguinal region, and a left orchiectomy was eventually performed. However, in this case the removal of the left testis was performed because of infection instead of malignancy since the histopathological examination of the left testis revealed only atrophy of germ cells without any atypia of either Leydig cells or germ cells.21\n\nAnother consideration regarding post-pubertal treatment is the presence of testicular torsion. The incidence of testicular torsion in uncorrected UDT is higher, which was proved by a case presented by McDermott et al. The authors described a 42-year-old man who had a bilateral UDT and a history of right orchidopexy and came with abdominal peritonism. Further investigation revealed a torted seminomatous testicular tumour from the previously neglected left testis.3,22 A study by Naouar et al. showed that adult patients with UDT and testicular torsion were managed based on the intraoperative finding of the testes. Orchiectomy was preferred when there was a mass or testicular necrosis, while orchidopexy was still an available choice for simple torsion.23\n\nIn addition, a study by Yuksel et al. described the possibility of persistent Müllerian duct syndrome (PMDS) in bilateral UDT. The article showed a 26-year-old male who presented with infertility and swelling of his right inguinal region. Further examination revealed a right inguinal hernia with bilateral UDT. The patient was then scheduled for a laparoscopic exploration, in which his right testis was found attached to a uterus by a round ligament and tuba uterina and his left testis was found atrophic and attached to the other side of the uterus. The left testis was then removed and a right orchidopexy was performed along with a right inguinal herniography. The presence of the uterus and bilateral tuba uterina was suggestive of PMDS, and a histopathological examination of his right testis revealed an intratubullary germ cell neoplasia.24\n\nThe possibility of PMDS in UDT was important because it could develop into a Müllerian malignancy and be fatal. A study by Farikullah et al. showed the importance of Müllerian remnant removal when performing orchidopexy. The study observed eight patients in a series that had PMDS and UDT. One of the patients was a 44-year-old male who had bilateral UDT and underwent bilateral inguinal exploration and a left orchidopexy at the age of 18. However, the Müllerian structure in this patient was not seen at the laparoscopy, resulting in a missed PMDS. The patient was then diagnosed with squamous cell carcinoma of the Müllerian duct 26 years later and died of metastasis.25 Therefore, a thorough investigation of Müllerian structure is important when performing orchidopexy, especially in the case of bilateral UDT, and any Müllerian remnant found during examination should be removed.\n\nThe limitation of this study is that the resources regarding post-pubertal treatment in UDT were scarce and the only articles available were case reports and observational studies with few research subjects, resulting in heterogeneity between studies. In addition, most of the articles were outdated and did not mention the pubertal status of the patients; thus, we could only assume the post-pubertal status based on the common age of male puberty, as described in the methods section. Nevertheless, this is the first systematic review providing treatment recommendations in post-pubertal UDT by considering the malignancy risk.\n\n\nConclusions\n\nTo conclude, in terms of malignancy risk, several factors should be considered when deciding post-pubertal UDT treatment, including the age of the patients, comorbidity of the patients, interest in fertility, and location of the testes. The authors recommend performing orchiectomy in post-pubertal unilateral UDT patients with normal contralateral testes, post-pubertal inguinal bilateral UDT patients that had no interest in fertility, and post-pubertal intraabdominal bilateral UDT patients aged less than 50 with no comorbidity or less than 35 with mild systemic disease. Otherwise, surveillance in patients older than 50 years old and orchidopexy in younger patients could still be considered. Therefore, it is important to clearly explain both the risks and possible benefits of both orchidopexy and orchiectomy to all post-pubertal UDT patients.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nOpen Science Framework: PRISMA checklist for article ‘Supine versus prone position in percutaneous nephrolithotomy: a systematic review and meta-analysis’, https://doi.org/10.17605/OSF.IO/K5QCJ. 7\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors would like to thank Cipto Mangunkusumo General Hospital for the support in the production of this article.\n\n\nReferences\n\nLeslie SW, Sajjad H, Villanueva CA: Cryptorchidism. [Updated 2023 Mar 11]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jan- Jan. Reference Source\n\nRadmayr C, Bogaert G, Burgu B, et al.: EAU Guidelines on Paediatric Urology. The Netherlands: EAU Guidelines Office; 2023.\n\nNiedzielski JK, Oszukowska E, Słowikowska-Hilczer J: Undescended testis - current trends and guidelines: a review of the literature. Arch. Med. Sci. 2016 Jun 1; 12(3): 667–677. PubMed Abstract | Publisher Full Text | Free Full Text\n\nViljoen JT, Zarrabi A, Van der Merwe A: Management of cryptorchidism in adolescent and adult males. Afr. J. Urol. 2020; 26: 40. Publisher Full Text\n\nMuncey W, Dutta R, Terlecki RP, et al.: Fertility potential in adult men treated for uncorrected bilateral cryptorchidism: A systematic literature review and analysis of case reports. Andrology. 2020 Dec 22; 9: 781–791. PubMed Abstract | Publisher Full Text\n\nBreehl L, Caban O: Physiology, Puberty. StatPearls. Treasure Island (FL): StatPearls Publishing; 2020 Aug 22. 2020 Jan-. Reference Source\n\nTendi W, Raharja PAR, Wahyudi I, et al.: Post-pubertal management of undescended testes from malignancy risk point of view: a systematic review 2023.Publisher Full Text\n\nLuchini C, Stubbs B, Solmi M, et al.: Assessing the quality of studies in meta-analyses: advantages and limitations of the newcastle ottawa scale. World J. Meta Anal. 2017; 5: 80–84. Publisher Full Text\n\nMa LL, Wang YY, Yang ZH, et al.: Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better? Mil. Med. Res. 2020 Feb 29; 7(1): 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTorricelli FC, Arap MA, Duarte RJ, et al.: Laparoscopic testicular preservation in adults with intra-abdominal cryptorchidism: is it beneficial? Adv. Urol. 2012; 2012: 329237. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFord TF, Parkinson MC, Pryor JP: The undescended testis in adult life. Br. J. Urol. 1985 Apr; 57(2): 181–184. Publisher Full Text\n\nPike MC, Chilvers C, Peckham MJ: Effect of age at orchidopexy on risk of testicular cancer. Lancet. 1986 May 31; 327(8492): 1246–1248. Publisher Full Text\n\nWobbes T, Schraffordt Koops H, Oldhoff J: The relation between testicular tumours, undescended testes, and inguinal hernias. J. Surg. Oncol. 1980; 14(1): 45–51. PubMed Abstract | Publisher Full Text\n\nFaruk M, Palinrungi MA, Kholis K, et al.: A giant intra-abdominal right testicular seminoma in a bilateral undescended testicle: a case report. Pan. Afr. Med. J. 2023 Jan 3; 44: 3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLopes RI, de Medeiros MT , Arap MA, et al.: Splenogonadal fusion and testicular cancer: case report and review of the literature. Einstein (Sao Paulo). 2012 Jan-Mar; 10(1): 92–95. PubMed Abstract | Publisher Full Text\n\nJacobellis U, Ricco R, Ruotolo G: Adenocarcinoma of the rete testis 21 years after orchiopexy: case report and review of the literature. J. Urol. 1981 Mar; 125(3): 429–431. PubMed Abstract | Publisher Full Text\n\nRohayem J, Luberto A, Nieschlag E, et al.: Delayed treatment of undescended testes may promote hypogonadism and infertility. Endocrine. 2017 Mar; 55(3): 914–924. PubMed Abstract | Publisher Full Text\n\nShin J, Jeon GW: Comparison of diagnostic and treatment guidelines for undescended testis. Clin. Exp. Pediatr. 2020 Nov; 63(11): 415–421. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu R, McQuaid JW, Paulson VA, et al.: Malignancy Yield of Testis Pathology in Older Boys and Adolescents with Cryptorchidism. J. Urol. 2022 Mar; 207(3): 694–700. PubMed Abstract | Publisher Full Text\n\nShah A, Feustel PJ, Knuth J, et al.: An updated mortality risk analysis of the post-pubertal undescended testis. Can. Urol. Assoc. J. 2018 Jul 24; 13(1): E1–E6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUeda H, Hirai K, Iwamoto Y, et al.: A case of testicular tumor associated with the contralateral undescended testis. Hinyokika Kiyo. 1995 Dec; 41(12): 1015–1018. PubMed Abstract\n\nMcDermott FD, Heeney A, Kelly ME, et al.: Torsion of an intraperitoneal undescended seminomatous testicular tumour. BMJ Case Rep. 2014 Jun 25; 2014: bcr2014203541. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNaouar S, Braiek S, El Kamel R: Testicular torsion in undescended testis: A persistent challenge. Asian J. Urol. 2017 Apr; 4(2): 111–115. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYuksel B, Saygun O, Hengirmen S: Persistent müllerian duct syndrome associated with irreducible inguinal hernia, bilateral cryptorchidism and testicular neoplasia: a case report. Acta Chir. Belg. 2006 Jan-Feb; 106(1): 119–120. PubMed Abstract | Publisher Full Text\n\nFarikullah J, Ehtisham S, Nappo S, et al.: Persistent Müllerian duct syndrome: lessons learned from managing a series of eight patients over a 10-year period and review of literature regarding malignant risk from the Müllerian remnants. BJU Int. 2012 Dec; 110(11 Pt C): E1084–E1089. Publisher Full Text"
}
|
[
{
"id": "252570",
"date": "25 Mar 2024",
"name": "Biagio Barone",
"expertise": [
"Reviewer Expertise Urology and Andrology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral comment The manuscript entitled \"A Systematic Review on Post-Pubertal Management of Undescended Testes: Focus on Malignancy Risk” presents a systematic review on the management of undescended testes in post-pubertal individuals, with a focus on the risk of malignancy. The manuscript is well-structured and addresses an important clinical issue. However, there are areas for improvement in clarity, methodology, and interpretation of results.\nWhile the manuscript generally provides clear descriptions of methods and results, some sections could benefit from improved clarity and organization. Check grammar and sentences along the text. The authors appropriately acknowledge heterogeneity among included studies but should further discuss potential sources of heterogeneity and its impact on the synthesis of findings. About the risk of malignancy related to undescended testes, also see: [1] The review should explicitly address its limitations, such as its reliance on observational studies and the potential publication bias of studies reported. This will ensure a balanced interpretation of the evidence. The recommendations provided in the conclusion should be supported by a more robust synthesis of evidence, including consideration of potential biases and uncertainties.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "11793",
"date": "25 Jun 2024",
"name": "William Tendi",
"role": "Author Response",
"response": "1. Thank you for your kind review. We have revised the manuscript accordingly especially in the Introduction and Discussion sections 2. Thank you for your kind review. We have discussed further the heterogeneity on the Discussion section, paragraph 15 and Conclusion section 3. Thank you for your kind suggestion. We have added and cited additional information from the suggested articles at the Discussion section, paragraph 9, reference number 20 4. Thank you for your review. We have discussed the limitation of the study and potential bias in the Discussion section, paragraph 15-16 5. Thank you for your review. We have revised the Conclusion section accordingly"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1226
|
https://f1000research.com/articles/13-1357/v1
|
12 Nov 24
|
{
"type": "Genome Note",
"title": "The complete mitogenome of an unidentified Oikopleura species",
"authors": [
"Johannes Nicolaus Wibisana",
"Charles Plessy",
"Nicolas M. Dierckxsens",
"Aki Masunaga",
"Jiashun Miao",
"Nicholas Luscombe",
"Johannes Nicolaus Wibisana",
"Nicolas M. Dierckxsens",
"Aki Masunaga",
"Jiashun Miao",
"Nicholas Luscombe"
],
"abstract": "Appendicularians are planktonic tunicates abundant all over the world. Currently, only two complete annotated mitochondrial genome assemblies are available for appendicularians, both for cryptic species of Oikopleura dioica. This underrepresentation of available appendicularian mitochondrial genomes limits environmental DNA sequencing (eDNA) studies that rely on mitochondrial markers as a taxonomic barcode. We report the complete mitochondrial genome assembly and annotation of an unknown appendicularian species isolated from the Amami Oshima island, Kagoshima prefecture, Japan, that has significant sequence difference with other currently available assemblies and will serve as a useful resource for ecological studies and further mitochondrial studies of appendicularians.",
"keywords": [
"tunicate",
"larvacean",
"appendicularian"
],
"content": "Introduction\n\nAppendicularians (synonym: larvaceans) are tunicates distributed all over the world’s ocean that do not have a sessile stage, remaining free-swimming throughout its life cycle, and construct a cellulose “house” which is used for feeding and protection.1 The best studied appendicularian is the ~4 mm length O. dioica, 2 but there are also large species with a body size ranging between 3–10 cm.3 Appendicularian mitochondrial genomes use the ascidian mitochondrial genetic code,4–8 which differs from the invertebrate one by the reassignment of AGR codons from serine to glycine. In one clade within appendicularians containing O. dioica, homopolymers interrupt coding sequences and are resolved to hexamers by an unknown editing process.4–6 In this study, we sequenced the mitochondrial genome of an unknown appendicularian species sampled from the Amami Oshima island, Japan (Figure 1), in order to increase the taxonomic power of eDNA studies based on the sequence of mitochondrial genes.\n\nPhotographs of a specimen of the unidentified Oikopleura species preserved in 70% EtOH of (A) the whole body and (B) the trunk. Photos were taken by Dr. Yongkai Tan.\n\n\nMethods\n\nWe collected specimens at Tamari harbor, Amami Oshima island, Kagoshima prefecture, Japan (28.41491667 N 129.59016667 E) in July 2023. An identical specimen from the same catch was deposited at the Kagoshima University Museum (www.museum.kagoshima-u.ac.jp) under the voucher number KAUM-UR 1, the original specimen was consumed for sequencing. DNA extraction was done by firstly washing samples with 5 mL of filtered autoclaved seawater 3 times before resuspending in 200 μl of lysis buffer from the MagAttract HMW DNA Kit (Qiagen, USA #67563) with 20 μL of 10 μg/mL proteinase K and incubated for 1 h at 56°C. Next, 50 μL of 5 M NaCl was added before centrifugation of the mixture (5000 × g at 4°C) for 15 min. The supernatant was transferred into a new microtube and mixed with 400 μL of 100% EtOH and 5 μL of glycogen (20 mg/mL) and cooled at -80°C for 20 min. Further centrifugation at 6250 × g, 4°C for 5 min was performed and the supernatant removed. The obtained pellet was then washed with 1 mL of cold 70% ethanol, centrifuged, and air-dried for 5 min. The DNA was then resuspended in nuclease free water and quantified using a Qubit 3 Fluorometer (Thermo Fisher, USA). Quality control of obtained DNA was performed using Agilent 4200 TapeStation (Agilent, USA). The sequencing was performed on a PacBio® Sequel II sequencer (Pacific Biosciences, USA).\n\nThe sequenced reads were assembled with NOVOLoci (https://github.com/ndierckx/NOVOLoci). A partial PacBio read sequence found by a BLAST9 search of cytochrome c oxidase subunit 1 from Okinawa O. dioica5 to the raw whole DNA reads was used as a seed sequence. An initial assembly revealed two haplotypes. We assembled them separately by using new seeds extracted from the regions that contain the polymorphisms in forward and reverse direction and concatenated the assembled sequences. The coverage plot was generated by mapping the sequencing reads that were used to assemble the mitogenome to the assembly itself using minimap version 2.28-r1209.10\n\nWe annotated the assembly with MITOS2 v2.1.911 using the ascidian mitochondrial genetic code.7 ARWEN version 1.2.312 was used in addition to annotate putative tRNAs.\n\nProtein-coding mitochondrial sequences were extracted from GenBank records with EMBOSS13 and codon-aligned manually in SeaView 5.0.514 after a first alignment with Clustal Omega version 1.2.4.15 The phylogenetic tree was computed with IQ-TREE version 2.0.716 using the command-line options -T AUTO --runs 3 --polytomy --ufboot 1000 -m MFP, with one partition per gene. Sequences, accession numbers, and trees are available in the supplemental material and on Zenodo (doi:10.5281/zenodo.13864550).\n\n3D protein structure was predicted using colabfold version 1.5.517 and visualized with PyMOL.18 UCSF ChimeraX19 can be used as an alternative to PyMOL.\n\n\nResults and discussion\n\nWe noticed large appendicularians during a sampling trip targeting O. dioica in the Amami Oshima island, Kagoshima, Japan. We took the opportunity to collect several of these large appendicularians and sequenced a single individual, from which we assembled a circular mitogenome of 13,058 bp length (Figure 2). We mapped the fraction of sequencing reads that were used for the assembly to the assembled sequence and obtained a sequencing depth between 36–176 × and an average depth of 122.4 × (Fig. S1).\n\nCircular plot generated by Geneious Prime version 2024.0.5. Protein coding genes and tRNAs are displayed on a yellow and pink background respectively. The circle in the middle illustrates the homopolymers; 6 or more successive Ts (forward) or As (reverse) in red and Cs (forward) or Gs (reverse) in blue. The inner circle indicates polymorphisms between the two haplotypes that we sequenced. Abbreviations as follows, cox2: cytochrome c oxidase subunit 2, nad5: NADH dehydrogenase subunit 5, cob: cytochrome b, nad4: NADH dehydrogenase subunit 4, nad1: NADH dehydrogenase subunit 1, putative nad2: putative NADH dehydrogenase subunit 2, atp6: ATP synthase Fo subunit 6, cox1: cytochrome c oxidase subunit 1, cox3: cytochrome c oxidase subunit 3.\n\nThe mitogenome does not possess stretches of homopolymers like the ones observed in O. dioica. There is also no evidence of mitochondrial introns. Thus, we could translate its open reading frames (ORFs) with no interruptions. We found a total of 9 protein coding genes, two pseudogenes (fragments of cox3) and 2 tRNA genes, all on the same strand (Table S1), but could not annotate ribosomal RNA genes, although the length of the remaining unannotated regions suggest that they may be present. We were only able to detect tRNA genes for Leucine and Valine.\n\nEight out of the nine protein-coding genes match known mitochondrial proteins without ambiguity. We also found an ORF with homology to the putative NADH dehydrogenase 2 (nad2) reported by Klirs et al.,6 and we also found matches in other appendicularian species, confirming its presence across Oikopleuridae (Fig. S2). Searches using BLASTp on the non-redundant protein sequences database did not yield hits, and a tBLASTx search on whole-genome shotgun contigs database of tunicates (taxid:7712) matched a predicted Oikopleura longicauda mitochondrial contig (SCLD01139119.1) which is different from the one we used for the phylogenetic analysis and misses some of the eight expected mitochondrial proteins. The predicted structure of the putative nad2 using colabfold17 consists of alpha helices (Fig. S3), similar to reported nad2 protein from human (PDB IDs: 5XTC chain Q). This observation might have been caused by tunicates having fast evolving mitochondria,20 and the coverage gap in the database that currently is available.\n\nWe extended the automatic gene annotation to the longest ORF which has stop codons (TAA, TAG) and start codons (TTG, ATA, ATG, GTG) accepted by the ascidian mitochondrial code.7 Nevertheless, due to the variability of initiation tRNA, we cannot rule out the possibility of the translation start codon being different, for example Halocynthia roretzi uses ATT as a start codon.21\n\nFrom the same individual we found a second distinct mitogenome with several single nucleotide and insertion or deletion differences, exclusively in non-coding regions (Figure 2). We chose the mitogenome with the major variant (63% vs 37%) for the analysis performed in this study. Furthermore, these two haplotypes are supported by homopolymer variants at multiple different loci. Possible explanations for this result are heteroplasmy or that the mitogenome consists of concatemers.\n\nThe codon usage (table S2) shows that, while TGA codes for tryptophan in tunicates, it is used in less than 5% of the tryptophan positions. Furthermore, these TGA codons were only found in the most N-terminal region of cox2, which is not well supported by alignment to other appendicularians and has a possible alternative start site downstream of these codons. Thus, depending on the real position of cox2’s translation start site, it is possible that the TGA codon is not used in this genome, similar to what was reported for O. longicauda on the cox1 and cob genes.7 Other than that, there are several other codon biases, such as towards TTG (39.7% and TTA (30.4%) for leucine. Another bias is present towards GTG that is coding for valine (56.7%).\n\nThe phylogenetic tree using protein-coding mitochondrial sequences (Figure 3) shows that this unknown species belongs to the clade of larvaceans that includes Bathochordaeus, Mesochordaeus and Oikopleura longicauda but not O. dioica. This clade was also found in a phylogenetic analysis of ribosomal protein sequences.22 The split between O. dioica and the other appendicularians in our tree corresponds to the bioluminescent/non-bioluminescent classification of Galt et al., 1985.23 This is also reflected in the situation of homopolymers which are not abundant in this mitogenome, similar to O. longicauda22 and not O. dioica.5 As the Oikopleura genus is polyphylic in our phylogenetic anaylysis and that of others, further work not in the scope of this manuscript will be needed to resolve which genus has to be corrected.\n\nPhylogenetic tree computed on codon-aligned mitochondrial genome protein-coding genes collected from publicly available aquatic chordate genomes.\n\nAs a final attempt to identify the species of this appendicularian, we extracted the sequence of the nuclear ribosomal RNA gene from one sequence read (see supplemental material), which we used to screen the GenBank database. The best hit (MK621860) has 1757 identical nucleotides over a length of 1773 (99%), and is from an O. fusiformis individual sampled in Croatia.\n\n\nConclusion\n\nWe present here the complete mitogenome of an unidentified Oikopleura species. Our phylogenetic analysis and the lack of homopolymer insertions show that it is closer to the lineage of O. longicauda than to the one of O. dioica. Morphological sumilarity and a preliminary analysis using nuclear genome rRNA sequences suggest that this unknown larvacean is most closely related to O. fusiformis, however as our recent studies of O. dioica24,25 uncovered cryptic speciation in appendicularians, and in the absence of specimen preservation allowing for confident taxonomic identification, we refrain from naming the species at this current stage. We project that the data produced in this study will be useful in future eDNA studies.\n\n\nEthical approval\n\nEthical approval and consent were not required.\n\n\nAuthor contributions\n\nJNW, CP, and NML conceived the study. AM and JM collected samples and AM performed sequencing. JNW, ND, and CP performed bioinformatics analysis. JNW drafted the manuscript. CP, ND, and NML critically revised the manuscript. All authors approved the final manuscript and agreed to be accountable for all aspects of this work.",
"appendix": "Data availability statement\n\nThe mitochondrial genome sequence was deposited in GenBank under the accession number LC830956. The associated BioProject, SRA, and Bio-Sample numbers are PRJNA1152617, SRR30429256, and SAMN43370082 respectively. The annotation and the sequences used to compute the phylogenetic tree in Fig. 3 are available in Zenodo (doi:10.5281/zenodo.13864550).\n\nAccession numbers\n\nNCBI Nucleotide database: Oikopleura sp. bigama1 mitochondrial DNA, complete genome. Accession number; LC830956. https://www.ncbi.nlm.nih.gov/nuccore/LC830956.1/.\n\nNCBI SRA: Genome sequencing of an unknown Oikopleura species.\n\nAccession number; PRJNA1152617. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1152617/.\n\nNCBI BioSample: Invert. https://www.ncbi.nlm.nih.gov/biosample/?term=SAMN43370082ebrate sample from Oikopleura sp. bigama1. Accession number; SAMN43370082\n\nNCBI Sequence Read Archive (SRA). WGS of Oikopleura sp. bigama1 Accession number; SRR30429256. https://www.ncbi.nlm.nih.gov/sra/?term=SRR30429256\n\nZenodo: Supplemental material to the journal article “The complete mitogenome of an unidentified Oikopleura species”. doi:10.5281/zenodo.13864550.26\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWe thank Dr. Michael Mansfield for the invaluable suggestions and guidance in the construction of the phylogenetic tree, Dr. Yongkai Tan for providing photographs of the specimens and Dr. Rade Garić for critical insights on sequence and morphological similarities to O. fusiformis. We thank the DNA Sequencing Section and the Scientific Computing and Data Analysis Section of the Research Support Division at OIST for their support.\n\n\nReferences\n\nKimura S, Ohshima C, Hirose E, et al.: Cellulose in the house of the appendicularian Oikopleura rufescens. Protoplasma. 2001 Mar; 216(1–2): 71–74. PubMed Abstract | Publisher Full Text\n\nGlover JC: Oikopleura. Curr. Biol. 2020 Oct; 30(20): R1243–R1245. Publisher Full Text\n\nSherlock RE, Walz KR, Schlining KL, et al.: Morphology, ecology, and molecular biology of a new species of giant larvacean in the eastern North Pacific: Bathochordaeus mcnutti sp. nov. Mar. Biol. 2017 Jan; 164(1): 20. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDenoeud F, Henriet S, Mungpakdee S, et al.: Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of a Pelagic Tunicate. Science. 2010 Dec 3; 330(6009): 1381–1385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDierckxsens N, Watanabe K, Tan Y, et al.: Tracing Homopolymers in Oikopleura dioica’s mitogenome. Genome Biol. Evol. 2024 Aug 20; 16: evae182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlirs Y, Novosolov M, Gissi C, et al.: Evolutionary Insights from the Mitochondrial Genome of Oikopleura dioica: Sequencing Challenges, RNA Editing, Gene Transfers to the Nucleus, and tRNA Loss. Genome Biol. Evol. 2024 Sep 3; 16(9): evae181. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPichon J, Luscombe NM, Plessy C: Widespread use of the “ascidian” mitochondrial genetic code in tunicates. F1000Research. 2020 Apr 14; 8: 2072. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYokobori S, Ueda T, Watanabe K: Codons AGA and AGG are read as glycine in ascidian mitochondria. J. Mol. Evol. 1993 Jan; 36(1): 1–8. PubMed Abstract | Publisher Full Text\n\nAltschul SF, Gish W, Miller W, et al.: Basic local alignment search tool. J. Mol. Biol. 1990 Oct; 215(3): 403–10. Publisher Full Text\n\nLi H: Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics. 2018 Sep 15; 34(18): 3094–3100. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBernt M, Donath A, Jühling F, et al.: MITOS: Improved de novo metazoan mitochondrial genome annotation. Mol. Phylogenet. Evol. 2013 Nov; 69(2): 313–319. PubMed Abstract | Publisher Full Text\n\nLaslett D, Canbäck B: ARWEN: a program to detect tRNA genes in metazoan mitochondrial nucleotide sequences. Bioinformatics. 2008 Jan 15; 24(2): 172–175. PubMed Abstract | Publisher Full Text\n\nRice P, Longden I, Bleasby A: EMBOSS: The European Molecular Biology Open Software Suite. Trends Genet. 2000 Jun; 16(6): 276–277. PubMed Abstract | Publisher Full Text\n\nGouy M, Guindon S, Gascuel O: SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building. Mol. Biol. Evol. 2010 Feb 1; 27(2): 221–224. PubMed Abstract | Publisher Full Text\n\nSievers F, Higgins DG: Clustal Omega. Curr. Protoc. Bioinformatics. 2014 Dec [cited 2024 Jul 4]; 48(1). Publisher Full Text\n\nMinh BQ, Schmidt HA, Chernomor O, et al.: IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol. Biol. Evol. 2020 May 1; 37(5): 1530–1534. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMirdita M, Schütze K, Moriwaki Y, et al.: ColabFold: making protein folding accessible to all. Nat. Methods. 2022 Jun; 19(6): 679–682. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchrödinger, LLC: The PyMOL Molecular Graphics System, Version 1.8.2015.\n\nMeng EC, Goddard TD, Pettersen EF, et al.: UCSF ChimeraX: Tools for structure building and analysis. Protein Sci. 2023 Nov; 32(11): e4792. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingh TR, Tsagkogeorga G, Delsuc F, et al.: Tunicate mitogenomics and phylogenetics: peculiarities of the Herdmania momus mitochondrial genome and support for the new chordate phylogeny. BMC Genomics. 2009 Dec; 10(1): 534. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGissi C, Pesole G: Transcript Mapping and Genome Annotation of Ascidian mtDNA Using EST Data. Genome Res. 2003 Sep; 13(9): 2203–2212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNaville M, Henriet S, Warren I, et al.: Massive Changes of Genome Size Driven by Expansions of Non-autonomous Transposable Elements. Curr. Biol. 2019 Apr; 29(7): 1161–1168.e6. PubMed Abstract | Publisher Full Text\n\nGalt CP, Grober MS, Sykes PF: Taxonomic Correlates of Bioluminescence Among Appendicularians (Urochordata: Larvacea). Biol. Bull. 1985 Feb; 168(1): 125–134. Publisher Full Text\n\nMasunaga A, Mansfield MJ, Tan Y, et al.: The cosmopolitan appendicularian Oikopleura dioica reveals hidden genetic diversity around the globe. Mar. Biol. 2022 Nov 27; 169(12): 157. Publisher Full Text\n\nPlessy C, Mansfield MJ, Bliznina A, et al.: Extreme genome scrambling in marine planktonic Oikopleura dioica cryptic species. Genome Res. 2024 Apr 15; 34: 426–440. genome;gr.278295.123v1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWibisana JN, Plessy C: Supplemental material to the journal article “The complete mitogenome of an unidentified Oikopleura species” (1.1.0). [Dataset]. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "341080",
"date": "06 Jan 2025",
"name": "Carmela Gissi",
"expertise": [
"Reviewer Expertise mitogenomics",
"tunicate evolution",
"long read NGS"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper describes the sequencing and assembly of the mitochondrial genome of a larvacean of the genus Oikopleura and also reports the mitochondrial phylogenetic analysis of Larvacea together with other chordate representatives. The manuscript is clear and well written, but need to be improved with details on the sample and the applied protocols as well as with additional evolutionary analyses\nI suggest to better stress in the introduction the need to sequence other larvacean representatives, not only for eDNA studies but also for evolutionary studies aiming at understanding the origin of chordates and tunicates, and to unravel the hidden biodiversity of Larvacea, a quite neglected taxon\nWas the DNA extracted from a single specimen preserved in 99% ethanol or at -80 °C? In the Methods section, the Authors reports that \"Quality control of obtained DNA was performed using Agilent 4200 TapeStation (Agilent, USA). The sequencing was performed on a PacBio® Sequel II sequencer (Pacific Biosciences, USA).\" Further details should be added. In particular, the Authors should report the ng and quality (i.e., absorbance values, TapeStation fragment profile) of the extracted DNA, the used PacBio library and sequencing kits, and the PacBio protocol used. Indeed, I suppose it was used the PacBio ultra-low input protocol, and, if so, how was the DNA fragmented?\nAs for the phylogenetic tree, it seems that it was reconstructed using all 13 protein-coding genes, including those absent in larvaceans. Moreover, the tree was reconstructed from nucleotide, not from amino acid sequences, as is common when long evolutionary distances are analyzed, in order to avoid substitution saturation phenomena. I suggest reconstructing the tree also from amino acid sequences, with/without the protein-genes absent in larvaceans, so considering only positions without gaps and then to compare the obtained trees. Bayesian trees should also be reconstructed to confirm the obtained phylogeny\nA well formatted \"full version\" of the tree of Figure 3 should be provided in the Supplementary Material. Although out of the scope of the paper, a brief comment on the recovered tunicate phylogeny should be reported\nThe Zenodo Supplementary material contains a folder with the results of IQ-TREE and RaxML analyses: could you please comment if there were differences between the trees obtained with the two methods? For not-users of the IQ-TREE software, I suggest explaining the meaning of the used command-line options and reporting that this software performs ML tree reconstructions The Authors should clarify the legend of Figure 3, including the number of genes analysed, the length of the alignment, the method and model used for the tree reconstruction. \"Possible explanations for this result are heteroplasmy or that the mitogenome consists of concatemers \": please explain better why you hypothesize the existence of concatemers. \"As the Oikopleura genus is polyphylic in our phylogenetic analysis and that of others,...\" : the Authors should cite the references where the Oikopleura genus was already found as polyphyletic \"Furthermore, these two haplotypes are supported by homopolymer variants at multiple different loci\": a table with all variants between the two haplotypes should be reported in the Supplementary Material, particularly if Figure 2 shows only a portion of these variants. I suggest making available in NCBI also the second assembled haplotype\n\nAre the rationale for sequencing the genome and the species significance clearly described? Partly\n\nAre the protocols appropriate and is the work technically sound? Partly\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Yes",
"responses": []
},
{
"id": "341076",
"date": "06 Jan 2025",
"name": "Ayelet Voskoboynik",
"expertise": [
"Reviewer Expertise genomic",
"evolution",
"comparative immunology and stem cell biology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper presents the mitochondrial genome assembly and annotation of an unknown appendicularian species collected from Japan. The findings contribute valuable data for future eDNA studies. The paper includes a thorough analysis of the mitochondrial genome including annotation and phylogenetics analyses. However, the paper is missing important metrics regarding the PacBio Sequel II sequencing results. Please address the following points to make the article scientifically sound: 1. Add the following metrics regarding the PacBio Sequel II sequencing results: HiFi Reads, HiFi Yield (bp), HiFi Reads Length (Mean bp), HiFi Read Quality (median), HiFi Number of Passes (mean), HiFi Reads Length Summary, HiFi Read Length Distribution. 2. Also include the stat for the assembly itself including: Contig type (Primary vs haplotigs; polished contigs; max contigs length; median contig length, N50 Contig Length, Sum of Contig length. 3. PacBio assemblers obtain circular contigs which include the mitochondria DNA (and bacteria DNA). If circular contigs were not utilized to directly obtain mtDNA, a brief explanation of the rationale for this decision would be valuable.\n\nAre the rationale for sequencing the genome and the species significance clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Partly\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1357
|
https://f1000research.com/articles/13-1356/v1
|
12 Nov 24
|
{
"type": "Study Protocol",
"title": "Protocol for a co-design study for the development of a chronotherapeutic mobile health behaviour change intervention targeting light exposure among older adults",
"authors": [
"Zahrah Alwi Alkaff",
"Resshaya Roobini Murukesu",
"Denz Del Villar",
"Manuel Spitschan",
"Zahrah Alwi Alkaff",
"Resshaya Roobini Murukesu",
"Denz Del Villar"
],
"abstract": "Through its wide-ranging effects on human physiology and behaviour, daily light exposure is an important environmental modulator of healthy ageing. Integrating mobile health (mHealth) technology with behaviour change strategies offers a promising approach to optimise light exposure and positively impact sleep, rest-wake cycles, cognitive function, and mood at scale. This study aims to develop the LightSPAN mHealth behaviour change intervention to optimise light exposure across the lifespan. Employing a co-design methodology, the study comprises two distinct workstreams. The first focuses on conceptualising the theoretical framework and implementation strategies through a comprehensive review of light exposure interventions, behaviour change theories, mHealth user personas, and recommendations for designing mHealth interventions for older adults. The second workstream centres on co-designing the intervention, involving consultation with community service providers and engagement with older adults at ageing community centres (≥60 years of age). Community service providers will be consulted through open-ended discussions (target n=5). Older adult participants (n=20) will engage in telephone interviews, focus group discussions and prototyping workshops to explore older adult participants’ characteristics, needs, preferences, and mHealth intervention design elements and co-design the LightSPAN mHealth behaviour change intervention. The insights generated in these co-design components will ensure that the intervention addresses the needs of its future users.",
"keywords": [
"Health Behaviour",
"Mobile Applications",
"mHealth",
"eHealth",
"Light",
"Light Exposure",
"Phototherapy",
"Patient Participation",
"Focus Groups"
],
"content": "Background\n\nPopulation ageing is a global megatrend. This is especially relevant to Singapore, where the proportion of older adults has nearly doubled, rising from 11.7% in 2013 to 19.1% in 2023.1 Furthermore, Singapore has one of the world’s highest life expectancies and is the only country within Southeast Asia to surpass a life expectancy beyond 80 years.2 However, living longer does not necessarily equate to living well. Unfavourable behavioural lifestyle practices have been shown to impact the quality of life, heighten susceptibility to chronic diseases, and shorten healthy life expectancy.3\n\nAdditionally, the evidence suggests low levels of awareness regarding the benefits of adopting favourable behaviour modification, even in later stages of life. These changes can enhance self-reliance and self-management skills, improving functional capabilities and mitigating the risk of adverse health outcomes.4 Hence, developing tailored lifestyle-oriented health interventions with embedded behaviour change elements into ageing-in-place strategies that align with daily living becomes increasingly essential to support healthy ageing, independence, and quality of life of older adults.\n\nLight is a fundamental environmental stimulus impacting numerous aspects of human physiology and behaviour. In addition to enabling one to see and perceive the world, the non-image-forming (NIF) effects of light5 include the alignment of the human internal biological clock to the environmental day/night cycle known as circadian rhythms, as well as the regulation of sleep patterns, alertness, mood, neuroendocrine activities, and cognitive functions.6 These effects are mediated by specialised photoreceptors in the retina referred to as intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs are particularly sensitive to light and serve as conduits in conveying information about ambient light conditions to the brain.7\n\nWith advancing age, significant changes in the visual system’s morphology and function occur progressively. These changes include a decrease in pupil diameter, a decrease in lens transmittance, presbyopia, the presence of vitreous floaters, and age-related macular degeneration.5,8 The decline in visual quality and function associated with ageing is characterised by decreased visual acuity, visual field sensitivity, contrast sensitivity, and increased dark adaptation threshold, attributed to age-related changes in retinal neural elements and ocular media.9 These various changes lead to reduced admittance of light into the eye, consequently impacting the perception and processing of light.5\n\nIn addition to the functional differences in visual ability, older adults face disruptions in their light exposure patterns due to decreased mobility, changes in sleep habits, and inadequate indoor lighting that can adversely affect well-being.6,10,11 Older adults are more predisposed to facing challenges in maintaining consistent sleep patterns and quality than younger adults.12–14 With advancing age, the decline in the central master clock’s efficiency and a decrease in melatonin secretion lead to fragmented rest-activity and sleep-wake cycles.5,15 The interplay of two systems, the sleep-wake homeostatic drive and the internal circadian clock, tends to be diminished in older adults, affecting the regulation of sleep-wake cycles.14,16\n\nIn addition to circadian entrainment and sleep, light influences cognitive function and mood through non-visual pathways. The limbic structures in the brain, namely the hippocampus and amygdala, activated by retinal light exposure, regulate mood and cognitive function.17 Moreover, the circadian and homeostatic sleep-wake regulating systems interact differently to affect human cognitive performance and mood.18 Exposure to bright light, particularly natural sunlight, enhances alertness, mood, and cognitive performance.7,19 Conversely, aberrant light exposure can lead to mood disturbances, fatigue, and impaired cognitive function.20,21 More critically, increased light exposure at night has been associated with a heightened risk of severe mental health conditions, including major depressive disorder, anxiety disorders, post-traumatic stress disorder, and self-harming behaviours.22\n\nLifestyle choices, social aspects, and environmental factors influence light exposure patterns.23 Thus, reduced admittance of light through the ageing retina, coupled with modifications in self-selected light exposure, lead to dysregulation in circadian rhythms, sleep-wake cycles, timing and quality of sleep, alterations in mood, behaviour, cognitive function, and increased susceptibility to morbidity and mortality in older adults.24,25 Ultimately, this leads to compromised well-being, alteration of the healthy ageing trajectory, diminished resilience, and premature mortality.\n\nTo address this, therapeutic approaches targeting the alignment of circadian rhythms may have protective benefits in preventing or mitigating age-related diseases.26 Evidence-based recommendations for healthy light exposure throughout the day have been developed for healthy adults.27 These recommendations highlight the importance of appropriate light exposure timing and the key concept of ‘bright days and dark nights’ to reap the benefits of light exposure27 but do not provide practical recommendations for realising these criterion levels. Hence, understanding the nuanced relationship between ageing and light exposure is essential for promoting healthy ageing trajectories and enhancing the quality of life for older adults.\n\nGiven the interplay between ageing, light exposure, and physiological outcomes, there is a pressing need for targeted interventions to optimise light environments to promote healthy ageing. Tailored interventions incorporating principles of chronobiology and light therapy, such as bright light therapy, environmental modifications, and timed exposure to daylight, have shown promise in improving sleep quality, cognitive function, and mood in older adults.8,28–32 While traditionally viewed as a passive environmental factor, light exposure is now seen as a dynamic behaviour, encompassing choices regarding various light sources and exposure times.33 Understanding light exposure through a behavioural lens can shape light exposure-related behaviours by empowering individuals to make informed decisions regarding their light exposure and inform targeted interventions.7\n\nDigital technologies have emerged as powerful tools in public health for promoting healthy lifestyles, with mobile health (mHealth) interventions standing out as promising avenues for facilitating behaviour change.34–36 Leveraging the increasing technical sophistication of mobile phones, mHealth offers accessible and scalable platforms for delivering targeted interventions.37,38 Pairing mHealth technologies with activity prescription has demonstrated favourable outcomes as a health promotion initiative aimed at preventing and mitigating the risk of lifestyle-related health outcomes.39 Recent systematic reviews have highlighted mHealth as an effective tool for promoting health behaviours, managing chronic conditions, and improving medication adherence.40–42 In Singapore, stakeholders have increasingly leveraged digital platforms to promote healthy behaviours.43 However, despite older adults’ interest in these interventions, challenges such as low confidence and anxiety regarding technology use, negative attitudes toward digital tools, trust and privacy concerns, limited digital literacy, and age-related limitations hinder user engagement.44–48 These challenges necessitate fine-tuned implementation strategies to optimise the accessibility, acceptability, and adaptability of mHealth interventions targeting ageing societies. Thus, mHealth interventions must be tailored to meet older adults’ needs and preferences, incorporating appropriate behaviour change strategies and undergoing iterative refinement based on user feedback and real-world data to enhance effectiveness and user satisfaction.38,49\n\nThe success of any intervention hinges on users’ adoption, adherence, and sustained engagement, which depends on technology’s capacity to overcome barriers and adapt to user needs and real-world contexts.50 The successful implementation of technology for ageing-in-place relies on prioritising the needs and wishes of older adults throughout the development and deployment phases, ensuring acceptance of the technology, delivering tangible benefits, and establishing favourable conditions conducive to using technology.51 Lived experiences as older individuals have been shown to offer invaluable insights often overlooked in technology development.52 Nonetheless, older adults have expressed an eagerness to learn and a willingness to engage in co-design initiatives.52\n\nCo-design is a collaborative approach where stakeholders such as users and community members are involved in the development and design process of products or interventions. This process is recognised for its ability to better address the population’s needs and yield better outcomes.53–55 It aligns with current policies, care practices, and the growing body of evidence highlighting the importance of engagement and co-design in health promotion interventions and digital solutions.53,56–58 Existing literature has established the utility of co-design, including a study that identified potential strategies and design alterations for a smartphone app through co-design workshops with people living with dementia and their care partners.59 Overall, studies co-designing technologies for health management, fitness, or in-home wellness have recognised the importance of including older adults as co-designers.60–62 Through sharing knowledge, experiences, and preferences, co-design optimises evidence-based interventions according to stakeholders’ priorities, ensuring maximum feasibility and sustainability.63\n\n\nThe LightSPAN Project\n\nThe LightSPAN project in Singapore tackles an essential aspect of healthy ageing by recognising the significant role of light exposure in regulating human health and quality of life. Amidst Singapore’s urbanisation, high population density, tropical climate, and growing elderly population, older adults face additional challenges compounded by age-related pathologies.43,64 These include restricted access to daylight, heightened exposure to artificial lighting, discomfort from the region’s heat and humidity, and the prevalent issue of light pollution.64,65\n\nTo address these challenges, the LightSPAN project is embarking on developing and testing an mHealth behaviour change intervention as an ageing-in-place strategy to empower older adults in Singapore, urging them to adopt light-friendly behaviours that can positively influence their health. The intervention utilises the LightSPAN mHealth app, which tracks light exposure using a light sensor and employs various behaviour-change strategies to optimise light exposure patterns, with the ultimate goal of harnessing the potentially protective effects of light exposure on circadian rhythms, sleep quality, mood regulation, alertness, and cognitive function in ageing individuals. Through this innovative approach, LightSPAN seeks to provide valuable insights into the potential efficacy of a technology-driven, lifestyle-oriented intervention in promoting well-being among the older adult population in Singapore.\n\nThe current study presents the protocol outlining the formative steps of LightSPAN’s smartphone-based behaviour change intervention designed to optimise light exposure across the lifespan. This endeavour is a precursor to a main randomised controlled trial (RCT), which will evaluate the intervention’s effects on various metrics, including changes over time in light exposure, sleep, mood and well-being, cognitive assessment, and biometric health measurements. A co-design approach will be employed to develop an effective mHealth intervention tailored to our target users, involving active collaboration between the researchers and older adult participants. Building upon the recognised importance of light as an environmental facilitator of healthy ageing, this study aims to develop an mHealth behaviour change intervention to optimise light exposure among older adults in Singapore via a novel mHealth application. Specifically, this study aims to:\n\n1. Conduct a literature search on light exposure interventions, behaviour change theories, mHealth user personas, and recommendations for designing mHealth interventions for older adults to conceptualise the theoretical framework and implementation strategies.\n\n2. Consult with community service providers to gather insights and feedback on the proposed intervention plan.\n\n3. Undertake a telephone interview to understand older adults’ current practices and preferences related to health, light exposure, and technology.\n\n4. Conduct focus group discussions (FGD) with older adults to explore their perspectives, needs, and preferences regarding light exposure, motivations for behaviour changes, and acceptance of mHealth interventions and gather feedback on the LightSPAN mHealth intervention plan.\n\n5. Conduct a prototyping workshop to present the prototype of the LightSPAN mHealth app, aiming to collect feedback for its iterative development and refinement.\n\n\nMethods\n\nThe present co-design will adopt a mixed-methods approach structured across two main workstreams. The study flow chart depicted below in Figure 1 outlines the co-design protocol, describing the progression from one workstream to another and the content explored at each stage.\n\n• Workstream 1: Conceptualization of the theoretical framework and implementation strategies\n\n○ 1a: Overview of Reviews\n\n○ 1b: Examination of mHealth personas\n\n○ 1c: Self-Determination Theory (SDT) behaviour change framework\n\n○ 1d: Recommendations for designing mHealth interventions for older adults\n\n• Workstream 2: Co-design of the mHealth intervention\n\n○ 2a: Consultation with community service providers\n\n○ 2b: Engagement with older adult participants\n\n▪ Telephone interview\n\n▪ Focus Group Discussion\n\n▪ Prototyping workshop\n\nThe co-design project team is comprised of a research team including a circadian vision neuroscientist (MS, PhD, male), a geroscientist (RRM, PhD, female), both with more than five years of experience in human research, as well as a research associate with training in cognitive neuroscience (ZAA, MSc, female), a research software engineer (DDV, BSc, male), and a clinical trial coordinator (NK, BSc, female), all with less than five years of experience in human research. During the discussions, the team will be assigned roles such as moderator, notetaker, and facilitator. The notetaker will use a template format based on the prior guidelines66 to ensure consistency in capturing session details and insights. These roles play a crucial role in facilitating productive co-design sessions and effectively gathering feedback from the participants.\n\nThe current study advocates for the inclusion of an additional construct focused on behaviour change to push beyond the envelope of merely developing an effective mHealth intervention but also one that is an integrated mHealth solution tailored to meet the unique needs and preferences of its users and creates sustained, long-term, positive health behaviour practice among older adults. In line with recommendations for person-based approaches to intervention development, we formulated guiding principles for the intervention design. These serve as a reference in the planning and development stages.67\n\nComprising two essential elements, they include intervention design objectives and key features crucial for achieving these aims. The first intervention design objective is to educate older adults on the importance of light exposure and its associated behaviours by developing informative content and materials and providing tools and resources that allow participants to make informed decisions about their light exposure habits, aligning interventions with their preferences and lifestyles. The second intervention design objective is to help older adults optimise their light exposure to support their health and well-being through mHealth by employing behaviour change techniques, including goal setting, self-monitoring, and feedback to encourage sustained engagement with the intervention by fostering autonomy, competence, and relatedness and adoption of healthy light exposure practices.\n\nOur approach’s key components are empowering participants to enhance their well-being through optimised light exposure, creating lifestyle-compatible practices, promoting self-efficacy and positive affect through encouraging and rewarding achievable goals, and providing support and strategies to overcome barriers. To facilitate this, tailored interventions must be delivered appropriately for older adults, considering the population’s cultural and circumstantial context, for behaviour change to be effectively harmonised within individuals’ lifetimes.68\n\nWorkstream 1: Conceptualization of the theoretical framework and implementation strategies\n\nAim: To conduct a literature search on light exposure intervention, mHealth user personas, behaviour change framework, and recommendations for designing mHealth interventions for older adults to conceptualise the theoretical framework and implementation strategies.\n\nThe first workstream is the cornerstone of the intervention development, laying the foundation for the subsequent workstreams. This involves carefully reviewing the literature to synthesise current evidence, ensuring it is informed by evidence-based practice. The research efforts within this workstream encompass four parts as follows.\n\nWorkstream 1a: Overview of Reviews\n\nIn Workstream 1a, we aim to address the research question: What are the effects of ocular light exposure on sleep, circadian rhythms, rest-activity cycles, mood, and cognitive function in older adults aged 60 years and above?\n\nA Cochrane Overview of Reviews will be undertaken to identify existing systematic reviews on light as a lifestyle intervention to enhance the health and well-being of older adults. This Overview of Reviews aims to comprehensively understand the efficacy and potential benefits of ocular light exposure in this demographic. Following the proposal approval of this Overview of Reviews from the Cochrane Database of Systematic Reviews, the protocol and review will follow the Cochrane Review guidelines. Preliminarily, we have identified a collection of existing systematic reviews that provide insight into ocular light exposure and health outcomes on older adults, specifically on sleep, circadian rhythms, rest-activity cycles, mood, and cognitive function.30,69–80 The findings in this Overview of Reviews will provide systematised scientific knowledge on how light exposure can support healthy ageing and develop an understanding of target light levels for optimal beneficial effects.\n\nWorkstream 1b: Examination of mHealth user personas\n\nWorkstream 1b aims to address the following research question: What are the distinct personas and associated characteristics of older adults aged 60 years and above in Singapore concerning their engagement with mHealth solutions?\n\nTo understand the diverse needs, preferences, and behaviours of older adults in Singapore regarding mHealth solutions, we conducted a purposive search for persona papers related to mHealth users, focusing on older adults in Singapore. This involved a thorough exploration to identify relevant studies and comprehensively review them to extract insights into the needs and preferences of older adults in Singapore concerning mHealth solutions. The search led to a study by Haldane et al.81 that identified five personas through 20 in-depth interviews and 100 survey responses: The Quiet Analog, The Busy Grandparent, The Socializer, The Newly Diagnosed, and The Hard-to-Reach. These personas delineate vital characteristics such as healthcare access, medication adherence, mobile phone technology usage, and interest in mHealth. By benchmarking this study, our goal is to enrich our understanding of user behaviours, preferences and needs within the context of our research.\n\nThe five personas highlight variability across various dimensions, including lifestyle, social factors, and mobile technology usage and needs. The personas also reveal behavioural variations in adherence among older adults and usability issues, illustrating how users interact with their phones in specific ways. Thus, to support uptake and adherence and effectively cater to the different personas, the intervention development must address varying levels of familiarity with mHealth, such as incorporating introductory sessions for those less familiar and having trusted providers facilitate the process. The personas also elucidated why certain groups may be hesitant to adopt mHealth interventions, thereby prompting exploring strategies to gain their buy-in or developing alternative or supporting measures to support them effectively. Lastly, a takeaway from the personas is that they can help facilitate focused discussions during design by prompting discourse on how each persona may respond to tasks, prompts, or calls to action. These personas are valuable tools, providing a tangible framework to conceptualise and empathise with our target demographic. Integrating insights from these personas ensures that our solutions are finely attuned to the diverse needs and preferences of older adults in Singapore, thereby enhancing the likelihood of successful uptake and adherence to our mHealth intervention.\n\nWorkstream 1c: Self-Determination Theory Behaviour Change Framework\n\nIn Workstream 1c, we seek to address the following research question: “What behaviour change model can be applied to optimise light exposure among older adults and promote sustainable behaviour change in this population?”\n\nFollowing the evaluation of various behaviour change strategies such as the Health Belief Model, Theory of Planned Behaviour, and The Transtheoretical Mode, the Self-Determination Theory (SDT) stands out as a prominent framework for understanding and promoting behaviour change in older adults, given its foundation in motivation and well-being, its wide use, along with the growing evidence of efficacy.82,83 Additionally, the SDT has particular relevance and effectiveness in addressing older adults. Its emphasis on autonomy and empowerment aligns well with the needs and preferences of this population, making it a suitable framework for promoting healthy behaviours and enhancing well-being in older age.84 The SDT was thus selected as the theoretical framework to guide the development of intervention and behaviour change strategies.\n\nThe SDT posits that human motivation is driven by three basic psychological needs: autonomy, competence, and relatedness. Individuals are intrinsically motivated to engage in activities fulfilling these needs, leading to greater persistence, satisfaction, and well-being.85 To exemplify, a study by Teas et al. posits that merely encouraging and partaking in physical activity was insufficient to improve well-being in older adults. It was emphasised that these activities must also fulfil their fundamental psychological needs.86 Extensive research has shown the effectiveness of interventions based on the SDT in health promotion, education, and workplace performance.87–91 Additionally, resources are available that elucidate the principles of the SDT and provide guidance for its application within the context of health, promoting and encouraging its utilisation.67,92\n\nWhen applied to the context of light exposure, the SDT offers valuable insights into the motivational factors that can drive individuals’ light-related behaviours. The LightSPAN Behaviour Change Model framework is formulated based on the insights derived from the SDT, as shown in Figure 2. The framework outlines the concepts by which we seek to foster autonomy, competence, and relatedness among participants, facilitating behaviour change in the context of light exposure.\n\nIn this framework, autonomy emphasises empowering individuals to make informed choices about their light exposure. This involves highlighting the importance of light for health and well-being and enabling participants to align their behaviour changes with their personal lifestyles and routines. By giving them control over implementing these changes, the intervention fosters a sense of ownership, making it more likely that participants will sustain their behaviour long-term.\n\nCompetence focuses on providing participants with the tools, education, and support needed to manage their light exposure effectively. This includes practical resources like light sensors and the LightSPAN mHealth app, which help participants track and adjust their exposure. The intervention also focuses on building knowledge, raising awareness of the benefits of optimal light exposure and equipping participants with the necessary skills to apply this knowledge. Additionally, tailored support ensures they have guidance to manage their progress confidently. This creates a sense of achievement and mastery as participants learn and apply new skills.\n\nRelatedness is addressed by fostering a sense of care, respect, and connection between participants and the intervention team. Through collaborative co-design, participants’ feedback and preferences are considered, making them feel valued and understood. The language and interactions used are friendly and compassionate, encouraging a positive and respectful atmosphere that supports participant engagement. This principle also ensures that the participants feel connected to the broader goals of the intervention and the community.\n\nThe intervention will incorporate fundamental techniques—self-monitoring, goal setting, feedback, and education—that are integrated to align with SDT principles of autonomy, competence, and relatedness. These techniques have been proposed to engage participants with technology and produce the desired behaviours. They have been shown to be effective in digital interventions across various studies,93–97 particularly in supporting self-efficacy and positively impacting behaviour.98,99 These techniques will work together within the LightSPAN mHealth app to create a cohesive and supportive intervention experience:\n\n▪ Self-monitoring empowers participants by giving them real-time data on their behaviour, allowing them to take control of their light exposure and make adjustments.\n\n▪ Goal setting helps participants personalise objectives, breaking changes into achievable steps that foster confidence and a sense of progress.\n\n▪ Feedback reinforces this progress by providing supportive insights and creating a caring environment that motivates continued engagement.\n\n▪ Education underpins these techniques, providing participants with the knowledge and skills needed to make informed decisions.\n\nTogether, these techniques foster a sense of empowerment, mastery, and connection, motivating participants to sustain long-term change by aligning their actions with their personal goals and feeling supported throughout the process.\n\nWorkstream 1d: Evidence-based recommendations for designing mHealth Interventions for older adults\n\nWorkstream 1d addresses the following research question: “What evidence-based recommendations can guide the design and implementation of mHealth interventions tailored to older adults?”\n\nTo ensure the efficacy of our mHealth interventions tailored to older adults, we explored mHealth studies and established best practices. This step aims to identify strategies that have effectively leveraged technology to address older adults’ health-related concerns. Through a review of the evidence, we searched for studies on digital and mHealth interventions and co-design studies involving older adults. From these studies, we extracted evidence-based recommendations to guide the design and implementation of our mHealth interventions. These recommendations were synthesised to inform our app’s development and design process, ensuring it aligns with practices conducive to promoting health among older adults.\n\nThe evidence-based recommendations will be infused into the intervention through these five broad categories: app features, engagement strategies, development methodologies, interface design, and support mechanisms, providing a structured framework to guide the design and implementation of the app suitable for older adults.\n\nIntegrating insights\n\nAfter thorough reviews and analyses of the evidence and available literature, we integrate our insights to inform the initial development phase and systematically guide subsequent steps in our project. This process informs the intervention design, focusing on developing the LightSPAN mHealth app. We aim to develop and present an evidence-based prototype of the smartphone application that aligns with the objectives and framework of the LightSPAN mHealth intervention, tailored to the needs of our target audience, and positioned to effectively promote healthy ageing.\n\nWorkstream 2: Co-design of the mHealth intervention\n\nWorkstream 2 centres on the collaborative design process of the mHealth intervention. It involves a comprehensive exploration of participant characteristics and needs alongside the design elements of mHealth interventions. To achieve this, we employ a multi-pronged approach consisting of several data collection methods. The first group comprises community service providers to seek their experience and knowledge to provide their insights and feedback on the proposed intervention plan. The second group comprises community-dwelling older adult participants who partake in telephone interviews, FGDs, and prototyping workshops.\n\nAs part of the development process, we have developed a Minimum Viable Product (MVP) version of the LightSPAN mHealth app, including the core functionalities to optimise light exposure. This MVP will serve as a baseline for iterative improvements based on feedback gathered throughout the co-design process. This version will be refined through focus group discussions, prototyping workshops, and feedback from participants.\n\nThese methodologies enable collaborative development of the LightSPAN intervention with the study team, ensuring the active involvement of older adults in shaping the app according to their needs and preferences.\n\nWorkstream 2a: Consultation with community service providers\n\nThe consultation with community service providers aims to gather insights and feedback on the proposed intervention plan tailored for older adults. Invitations will be extended to selected community service providers. During the consultation, the research team will present the proposed intervention plan and seek feedback, suggestions, and insights regarding the plan’s relevance, feasibility, and potential impact within the community setting. Discussions will cover potential barriers and facilitators to implementation, strategies for engagement and recruitment of older adults, and any additional considerations. Feedback collected during the consultations will help identify areas for improvement and refinement of the intervention.\n\nWorkstream 2b: Engagement with older adult participants\n\nStudy sample\n\nThe study will involve community-dwelling older adults in Singapore recruited via purposive sampling. Participants will be recruited from Active Ageing Centres (AAC) with the support of Lions Befrienders (LB), a social service agency in Singapore dedicated to providing care and support for older adults.100 The AACs are a drop-in social, recreational hub for older adults in the community in various neighbourhoods across Singapore. Upon recruitment, participants will receive a comprehensive information package containing an invitation letter, participant information sheet, consent form, and contact details of the research team. The target sample size for the co-design study is 20 older adult participants, guided by previous co-design studies.101,102 This sample will be divided into four groups comprising five participants. The participants and researchers will have no relationship prior to the study. Eligible participants will be recruited according to the inclusion and exclusion criteria, including smartphone use and demographic and mental and physical health parameters. The specific inclusion and exclusion criteria are outlined in Tables 1 and 2 below.\n\nThe data collection sessions will take place at the AACs designated by LB and will utilize dedicated discussion rooms. These rooms will be set up to ensure a conducive environment, prioritizing comfort, privacy, and minimal disruptions, ensuring optimal conditions for engagement with older adults.103\n\n\nScreening\n\nAt screening, demographic information will be obtained, including age, sex, ethnicity, marital status, education level, employment status, housing type, living arrangement, socioeconomic status, and contact information. Participants will also be screened for functional mobility, communication abilities, smartphone ownership, and health status.\n\nParticipant’s overall health will be assessed to determine health status, cognitive function, mental health, and ocular health. Table 3 presents the screening measures that will be administered for participant recruitment.\n\nTelephone interview\n\nAim\n\nThe preliminary telephone-based interview aims to understand older adults’ current practices and preferences related to health, light exposure, and technology.\n\nProcedure\n\nParticipants will receive a scheduled appointment for the telephone interview, communicated well in advance with a reminder closer to the appointed date and time. During the scheduled call time, participants will receive an introductory briefing over the phone, providing an overview of the study’s objectives to ensure a comprehensive understanding of the research aims. The telephone interview will proceed with administering questionnaires evaluating physical activity levels, and sleep quality. Additionally, the interview will include questions exploring participants’ practices and preferences regarding light exposure, smartphone use, and mobile health literacy. Participants’ responses will be carefully recorded to accurately capture all relevant information. The telephone interview is anticipated to last approximately 30 minutes.\n\nMeasurements & outcomes\n\nThe telephone interviews will serve as a platform for administering questionnaires on physical activity and sleep, as well as structured interview questions on light exposure and mHealth. By analysing the responses, we aim to gain insights into their status and identify common trends and patterns among the participants, thereby enhancing our understanding of their attitudes and behaviours before exposure to the LightSPAN mHealth intervention. This comprehensive overview of participant characteristics will inform subsequent stages of the study and guide the development of targeted interventions tailored to the needs and preferences of older adults. Table 4 and Table 5 outline the constructs that will be measured during the telephone interview using standardised questionnaires and structured interview questions.\n\nFocus group discussion\n\nAim\n\nThe FGD aims to explore older adults’ perspectives, needs, and preferences regarding light exposure, motivations for behaviour change, and acceptance of mHealth interventions. Also, the LightSPAN mHealth intervention will be introduced, and feedback on the proposed intervention plan will be gathered. This exploration aims to establish a foundational understanding of their perspectives, uncover potential challenges and opportunities for effective intervention uptake, and identify areas for improvement to bolster the intervention’s effectiveness and acceptance among the target users.\n\nProcedure\n\nThe session will commence with introductions and an icebreaker activity to foster a comfortable atmosphere conducive to open discussion. Participants will then be provided an overview of the FGD’s objectives to establish context and clarify expectations. Guided by the moderator, discussions will encompass various topics, including participants’ experiences and perceptions of light exposure, motivations for behaviour change, smartphone usage patterns, and acceptance of mHealth interventions. Participants will then be given the background of the LightSPAN project and the LightSPAN mHealth intervention plan, for which their feedback and initial acceptability will be sought. Subsequently, a guided questionnaire will be administered to gather preferences on various app components. The FGD will conclude with a wrap-up session summarising key points and outlining the next steps. The session will last 90 minutes, encompassing introductions, instructions, discussion, and wrap-up.\n\nMeasurements & outcomes\n\nThe FGDs will be guided by a developed script containing main questions and subsidiary prompts. The sessions will be audio recorded using a recording device and supplemented with notetaking to ensure thorough documentation of participants’ responses and interactions. The session covers three main components: user perceptions and attitudes, feedback on the LightSPAN mHealth intervention plan, and the feature preference questionnaire, detailed in the table below. Their responses will be meticulously analysed to identify recurring themes, patterns, and commonalities, thereby shedding light on critical issues, concerns, and preferences pertinent to light exposure management and mHealth interventions. These insights will serve as valuable inputs to inform further intervention development and app design iterations, facilitating the creation of a more effective and user-centric solution. Table 6 below presents the constructs that will be explored, the instruments that will be used, the administration details, and the specific outcomes that will be assessed during the FGD.\n\n\n\n• Awareness of light exposure and its impact\n\n• Daily practices\n\n• Barriers and facilitators\n\n\n\n• Factors influencing and inhibiting motivation to adopt healthy behaviour\n\n\n\n• Comfort levels with smartphone usage.\n\n• Perception of smartphone importance in daily life\n\n• Frequency of smartphone usage and typical activities\n\n• Perception of smartphone impact on daily life\n\n• Perceived ease or difficulty of smartphone usage\n\n\n\n• Participants' initial reactions to using a health monitoring smartphone app.\n\n• SDT: Feelings of autonomy, relatedness, and competence when using mHealth apps\n\n• TTF: Alignment between mHealth and participants' health management practices and needs.\n\n• TAM: Perceived usefulness, and ease of use, and usage behaviours of mHealth services (frequency and patterns of using mobile health services for managing health)\n\n\n\n• Initial thoughts on the intervention plan\n\n• Perception of incorporating a light sensor and wrist-worn fitness tracker into daily routine\n\n\n\n• Interest in participating.\n\n• Likelihood of participation\n\n• Perceived benefits of participating and beliefs in its effectiveness for achieving good light exposure.\n\n• Anticipation of enjoyment from participating in the intervention\n\n• Perceived utility of the app in addressing participants' needs and challenges related to light exposure.\n\n• Level of confidence in using the app and engaging with it\n\n• Perceived difficulty of participating in the intervention and anticipated challenges or obstacles\n\n\n\n• Calculation of FPQ responses across 4 components; app features, interactive components for app engagement, app usage and app support consisting of 34 items , each rated on a scale of importance and interest\n\nPrototyping workshop\n\nAim\n\nThe prototyping workshop aims to present the prototype of the LightSPAN mHealth app and collect feedback for its iterative development and refinement.\n\nProcedure\n\nThe prototyping workshop will be interactive, showcasing the prototypes of the LightSPAN mHealth app to the participants. The prototype includes the essential features and functionality for initial testing and user feedback. At the start of the workshop, participants will be briefed on the workshop’s goals and roles. The prototypes will be presented in a storyboard format, broken down into key user flows or scenarios. Each storyboard illustrates user actions, system responses, and interface elements. Participants will be encouraged to share their initial thoughts and provide detailed feedback, highlighting aspects they liked and disliked, assessing user flow navigation, and suggesting improvements or changes. Subsequently, participants will engage in a design preference voting activity, where they will be presented with mock-ups of design options. They will cast their votes for their preferred option, and the votes will be recorded. After collecting the votes, participants will be encouraged to share the reasoning behind their choices for deeper insights into their preferences. The workshop will conclude with a summary of key insights gathered and outline the next steps in development. The session will be allocated 90 minutes, including introductions, prototype activity, and session wrap-up.\n\nMeasurements & outcomes\n\nThe prototyping workshop seeks to gain critical insights from participants’ feedback, validate design choices, and identify areas for improvement. This process will involve pinpointing areas of strength that resonate positively with the participants and highlighting areas requiring refinement based on concerns or issues raised during the workshop. Additionally, the process will include identifying commonalities, trends, and areas of consensus or divergence among participants regarding the prototype designs.\n\nData will be documented primarily through participant verbatim comments and feedback on prototypes (audio data), votes, and researcher observations. The discussion guide, outlining key topics and questions, will structure the workshop, focusing on two main areas: user perceptions and feedback and design preferences. Table 7 provides a synthesis of the constructs that will be explored, along with the instruments that will be used, the administration details, and the intended outcomes during the prototyping workshop.\n\n\n\n• Initial impressions\n\n• Identification of likes and dislikes.\n\n• Perception of app's navigational flow\n\n• Identification of potential challenges and suggestions for refinement\n\n\n\n• Preference for design options indicated by participant votes.\n\n• Insight into factors influencing participant design choices\n\nThe qualitative and quantitative findings will be integrated to provide a holistic understanding of the co-design process and its outcomes.\n\nQuantitative data analysis will be conducted using R (version 2023-10-31), R Studio (version 2023.12.1+402),111 Python (version 3.12.1) or future versions112 if available at the time of analysis. This will enable the application of statistical techniques to analyse numerical data collected during the study, primarily descriptive statistics. Standard descriptive statistics, e.g., mean, standard deviation, minimum, and maximum, will be reported for all metric variables. Frequencies and percentages will be reported for categorical variables.\n\nQualitative data will be analysed using thematic analysis, a widely used method for identifying, analysing, and reporting patterns and themes within data. Participant verbatim discussions (audio data) will be transcribed and organised alongside detailed notes taken during the sessions to capture nuances and key insights. The analysis will be supported by software such as NVivo (Lumivero, United States), which aids in organising and managing qualitative data. Two independent data coders will be involved in the coding process, ensuring reliability and consistency in identifying themes and patterns.\n\nThe current study will yield a co-designed app and intervention program meticulously tailored to the needs of older adults, which will then be carried onto a randomised controlled trial (RCT) for further evaluation. The development process entails two components, each meticulously documented for academic dissemination. The first component is data obtained through the co-design process with older adults. A research paper will report this process, presenting the findings and analysis of their perspectives, preferences, and experiences. Concurrently, the second component is the development of the LightSPAN mHealth app. This process will also be documented to provide a detailed account of the technical aspects of the creation, including the utilisation of user-centric design principles and the underlying source code.\n\n\nDiscussion\n\nAs the global population ages, formulating and tailoring health interventions to meet the needs of older adults becomes increasingly vital. The LightSPAN project aims to highlight the importance of optimising light exposure in daily life between ageing, light exposure, and health outcomes, particularly among community-dwelling older adults in Singapore. Through a collaborative and iterative co-design process, we have outlined our framework to co-create an intervention attuned to this demographic’s unique needs and preferences. Intervening at the intersection of ageing and light exposure, the LightSPAN project, anchored in behaviour change techniques and mobile technology, seeks to empower older adults to actively manage their light exposure behaviours to promote overall well-being. However, in doing so, it is important to formulate and tailor the health intervention to meet the needs of older individuals.\n\nThe present co-design protocol delineates the formative steps of the LightSPAN project, presenting the systematic procedures undertaken to develop a mHealth behaviour change intervention to optimise light exposure among Singapore’s older adults. Engaging with older adults throughout the intervention design process is crucial to ensure their perspectives, needs, preferences, and user experiences are effectively accounted for. By considering both the characteristics of participants and the design elements of the mHealth interventions, we aim to carry out an intervention that maximises user engagement, adherence, and overall impact on health outcomes. Nonetheless, despite the promising potential of the LightSPAN project, engaging older adults in the co-design process may present inherent challenges, as reported in previous literature. These challenges include recruitment and retention difficulties, logistical and scheduling complexities, competing personal commitments, group dynamics, varying levels of motivation to participate, and disparities in literacy levels.113,114\n\nTo address these challenges, we have proactively incorporated several strategies into our protocol.60,113 These include partnering with community organisations to assist with recruitment, setting a date for the sessions several weeks in advance to accommodate participants’ schedules, providing participants with educational materials to enhance their understanding of the project, offering context and a clear overview of aims at the beginning of each session, clarifying roles, and incorporating mobility breaks to maintain engagement and prevent fatigue. Additionally, we will conduct guided surveys to assist older adults in completing questionnaires and ensure comprehension and accuracy. From the outset, we assess participants’ baseline technological and health literacy levels during the telephone interview stage to determine support requirements in conducting discussions with them. Furthermore, we aim to communicate using simple language and utilise visual aids to facilitate understanding while also scheduling sessions in the morning to coincide with participants’ peak alertness.\n\nAdditionally, we will maintain small group sizes to foster a conducive environment for participation. Moreover, we recognise the importance of building rapport and trust with participants and will pay special attention to establishing a good working relationship. From the researcher team’s end, debrief sessions will be conducted to review each session and contour the next steps in the development process accordingly.\n\nTo complete the co-design process and ensure the comprehensive development of the LightSPAN mHealth intervention, we will pilot-test the intervention as part of the final and third workstream. A pilot study is planned to evaluate the feasibility of the LightSPAN intervention before broader implementation. This pilot study will provide valuable insights into the practicalities of intervention delivery, user engagement, and potential areas for refinement. Subsequently, a post-pilot discussion will be conducted to explore participants’ perceptions and experiences and assess the usability and acceptability of the intervention to further refine the intervention. This iterative approach to intervention development ensures that the LightSPAN intervention remains responsive to the needs and preferences of older adult users.\n\n\nConclusion\n\nIn conclusion, the LightSPAN project presents a promising approach to optimising light exposure among older adults in Singapore. This co-design protocol outlines a systematic approach for developing an mHealth behaviour change intervention tailored to optimise light exposure among older adults in Singapore. Through engagement with older adults and key stakeholders, this protocol addresses various aspects of light exposure optimisation, incorporating insights from literature reviews, consultations, telephone interviews, focus group discussions, and interactive prototyping workshops. By actively involving community service providers and older adults in the co-design process, we aim to create an intervention that is not only evidence-based but also user-centred and culturally appropriate. The LightSPAN project seeks to improve the well-being and quality of life of older adults and contribute valuable insights to the field of mHealth interventions for healthy ageing.\n\nEthical approval has been obtained by the Parkway Independent Ethics Committee (PIEC) under approval number PIEC/2024/030, dated 2 October 2024. All procedures will adhere to the ethical principles outlined in the Declaration of Helsinki, including obtaining written informed consent from participants, ensuring confidentiality, and protecting participants’ rights, privacy and well-being.\n\n\nAuthor contributions\n\nConceptualisation: ZAA, RRM, MS\n\nFormal Analysis: ZAA, RRM\n\nFunding acquisition: MS\n\nMethodology: ZAA, RRM, MS\n\nProject administration: RRM, MS\n\nSoftware: DDV\n\nSupervision: MS\n\nVisualisation: ZAA, RRM\n\nWriting – original draft: ZAA\n\nWriting – review & editing: ZAA, RRM, DDV, MS",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\nThis protocol follows the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. 115\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nNational Population and Talent Division: Population in Brief 2023. Singapore: 2023; pp. 1–28. Reference Source\n\nThanh Trong N, Thi Dong N, Thi LP: Population aging and economic growth: evidence from ASEAN countries. Cogent Bus. Manag. 2024 Dec 31; 11(1): 2298055. Publisher Full Text\n\nZaninotto P, Head J, Steptoe A: Behavioural risk factors and healthy life expectancy: evidence from two longitudinal studies of ageing in England and the US. Sci. Rep. 2020 Apr 24; 10(1): 6955. 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PubMed Abstract | Publisher Full Text\n\nYesavage JA, Sheikh JI: 9/Geriatric Depression Scale (GDS): Recent Evidence and Development of a Shorter Version. Clin. Gerontol. 1986 Nov 18; 5(1–2): 165–173. Publisher Full Text\n\nWashburn RA, Smith KW, Jette AM, et al.: The physical activity scale for the elderly (PASE): Development and evaluation. J. Clin. Epidemiol. 1993 Feb; 46(2): 153–162. PubMed Abstract | Publisher Full Text\n\nBuysse DJ, Reynolds CF, Monk TH, et al.: The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research. Psychiatry Res. 1989 May; 28(2): 193–213. PubMed Abstract | Publisher Full Text\n\nTao D, Chen Z, Qin M, et al.: Modeling Consumer Acceptance and Usage Behaviors of m-Health: An Integrated Model of Self-Determination Theory, Task–Technology Fit, and the Technology Acceptance Model. Healthcare. 2023 May 25; 11(11): 1550. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMateria FT, Smyth JM: Acceptability of Intervention Design Factors in mHealth Intervention Research: Experimental Factorial Study. JMIR Mhealth Uhealth. 2021 Jul 26; 9(7): e23303. PubMed Abstract | Publisher Full Text | Free Full Text\n\nR Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2021. Reference Source\n\nVan Rossum G, Drake J, Fred L: Python reference manual.1995 [cited 2024 Oct 14]. Reference Source\n\nConstantin N, Edward H, Ng H, et al.: The use of co-design in developing physical activity interventions for older adults: a scoping review. BMC Geriatr. 2022 Aug 8; 22(1): 647. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCurran JA, Cassidy C, Bishop A, et al.: Codesigning discharge communication interventions with healthcare providers, youth and parents for emergency practice settings: EDUCATE study protocol. BMJ Open. 2020 May 11; 10(5): e038314. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTong A, Sainsbury P, Craig J: Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int. J. Qual. Health Care. 2007 Dec; 19(6): 349–357. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "344595",
"date": "26 Dec 2024",
"name": "Kiran Maini Gerhardsson",
"expertise": [
"Reviewer Expertise Environmental psychology",
"applied gerontology",
"and lgiht and health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview report\nDrawing on the title (co-design), I expected more active collaboration with stakeholders and target users throughout the study – from start to end. I would characterise the study as a two-part (or two-phase) development of a health-promoting intervention. The intervention targets light exposure among older adults. The first phase (referred to as Workstream 1 by the authors) consists of foundational activities resulting in an early prototype of a mobile phone application, which is followed by a second stage (Workstream 2), including continued development and evaluation by future community service providers and target users (community-dwelling older adults, age 60 and over). Thus, a co-design approach will be applied in the second phase. The intervention – delivered via a mobile app – will be refined between the two phases and within the second.\n\nI do not suggest any changes to the protocol but rather an explication of what the authors mean by a co-design approach (to justify the title), minor elaborations on some procedure details and that the Background section is shortened to make space for an extended paragraph on co-design, situating the current study in more detail in the area of co-design, (e.g., addressing the frequency of co-designers’ involvement, timing – where in the process – and influence on the design solutions).\nI look forward to reading the results when the study is completed. Light-related interventions directed at older adults are much needed.\nBelow are some questions asking for clarification or suggestions, hoping they will improve the manuscript before indexing.\nAbstract: “open-ended discussions”. Could you be more specific – workshops, group interviews, focus group discussions?\nAbstract (the final sentence): “... will ensure that the intervention addresses the needs of its future users.” Consider rephrasing to, for example: “facilitate future implementation”. You will probably not capture the needs of all future users (considering the rapid development of technology). However, a limited number of participants will certainly help to capture many potential issues.\nP. 3: (subtitle) “ageing health” –> “healthy ageing”. Also, this subsection could be shorter. A background section should not be overly long in a study protocol.\nP. 3: “Exposure to bright light, particularly natural sunlight, ...” Sunlight or daylight?\nP. 3: “To address this, ...” Challenges, issues?\nP. 4: “Overall, studies co-designing technologies for health management, fitness, or in-home wellness have recognised the importance of including older adults as co-designers.” Missing word: “studies of”?\nP. 4: “ensuring maximum feasibility and sustainability.” Word choice – maybe more cautious – “facilitating” or “promoting”. Considering the rapid technology development and often long co-design processes, it might be better to be a bit cautious.\nP. 4: Word choice: “urging them”. Maybe “supporting” or “encouraging them”?\nP. 4: “The intervention utilises the LightSPAN mHealth app...” Confusing – is the app already developed? Or should it be rephrased to “will be provided using the ...”\nP. 4: “... the potential efficacy of a technology-driven, lifestyle-oriented intervention ...”. There is a misalignment here in giving technology priority. Your intention is to develop a user-centred intervention to address lifestyle issues (“... the potential efficacy of a lifestyle-oriented intervention using smartphone technology...”).\nP. 5: “mHealth user personas, ...”. Using personas is a helpful initial tool in the early step of development until you have conducted the interviews with the target users. Have you also considered using the interview findings in the next step (workstream 2) to create project-specific personas? Personas based on your interviews might be more helpful for further developing the intervention than more generic user profiles.\nP. 5 and 6: The workstreams described on page 5 do not entirely reflect Figure 1 on page 6. For example, is the prototype developed before workstream 2 (as shown in Figure 1, \"initial development of LightSPAN mHealth app), or is it included in workstream 2 as the workstream title indicates on page 5 (\"Co-design og the mHealth intervention\")? Also, I find new terms in Figure 1 a bit confusing, such as \"LightSPAN Behaviour Change Model\" and \"infographic with recommendations for mHealth design\". In Figure 1, a LightSPAN mHealth prototype app is developed after engaging with community service providers but before engaging with older adults. The unclarities mentioned above make me wonder whether this is a co-design project or a user-centred development of intervention, including need assessments and user evaluations. Relating to this, in the conclusion on page 5, the authors write: \"A co-design approach will be employed to develop an effective mHealth intervention tailored to our target users, involving active collaboration between the researchers and older adult participants.\" But Figure 1 shows something slightly different: you will develop an early prototype – get feedback from the community service provider – refine the prototype - and then you will ask older adults about their needs and preferences – and finally get feedback on the prototype by older adults participating in focus groups. However, the procedure described in the study might be regarded as a co-design study in a weaker sense. Then, the authors could describe their definition of a co-design approach.\nP. 6: Co-design team. The co-design team, as named by the authors, includes researchers and a coordinator, but no stakeholders or target users as expected. Why not refer to the team as a research team?\nP. 6: \"The team will be assigned roles ...\" Do you mean during the workshop and focus groups? Will all team members participate? What is the difference between a moderator and a facilitator?\nP. 6: Guiding principles. The principles are well described and essential to the intervention's development. To achieve the design objectives, the authors highlight, for example, \"To facilitate this, tailored interventions must be delivered appropriately for older adults, ...\" I wonder if you have considered how you will manage input from the stakeholders or end users concerning intervention delivery. An app-based solution may not be ideal. What if they express preferences for in-person meetings? Or getting tech support (on more occasions than at the introductory session)? Or reading the intervention content on printed material? Would the design of the intervention be sufficiently flexible to accommodate such types of preferences? Will the participants be informed about the extent of their influence on delivery and design? Learning from the experience of engaging with older adults, I advise discussing such matters beforehand with the research team.\nP. 7: Figure 2. Primary outcomes: \"Improved sleep quality and quality(?)\"\nP. 7: Figure 2. How does “collaborative co-design” address “relatedness” for those future end users who have not been part of the development? The SDT is used as a behaviour change model, which “can be applied to optimise light exposure among older adults and promote sustainable behaviour change in this population”. But “relatedness”, as described by the authors, refers to the developmental phase, not the use phase. I can think of some examples of “relatedness” in the use phase, such as in-person meetings, a community chat group for exchanging ideas about routines to increase daily light exposure or encouraging joint walks outdoors.\nP. 9-10: A clarification is needed. Is the outcome after workstream 1 an early prototype of a smartphone application? It would be good to make it explicit in Figure 2 (the prototype is not mentioned here until after Workstream 2). Or is it the “Minimum Viable Product (MVP) version of the LightSPAN” first described in workstream 2?\nP. 10: How will the community service providers be selected (any inclusion criteria?)? How will their feedback on the early prototype be collected - through workshops, focus groups, individual interviews, or other collection techniques? The study sample, including the older adults, is described in detail, unlike the sample which includes the community service providers.\nP. 10: Study sample: Why will the sample, including 20 participants, be divided into four groups? Is it because there will be five focus groups with five participants in each group?\nP. 13: The purpose of the telephone interviews with 20 older adults is to understand better their current light exposure behaviour and preferences regarding health and technology. How exactly will the findings inform the subsequent stages of the study and the development of the intervention (“serve as a platform”)? Is there an iteration missing in Figure 1? Or will the findings from the telephone interviews guide the development of the focus group interview guide? On page 18 (Discussion), the authors provide a much more apparent reason for including the telephone interviews: “We assess participants’ baseline technological and health literacy levels during the telephone interview stage to determine support requirements in conducting discussions with them.”\nP. 13: The focus group discussion aims to get feedback on user perceptions and attitudes, feedback on the LightSPAN mHealth intervention plan, and feature preferences. How many participants are there in each focus group? I assume not all 20 participants take part in one focus group.\nP. 15-16: Check the placement of Tables according to the in-text reference to, for example, Table 7.\nP. 17: How many will take part in the prototyping workshop when the participants evaluate and discuss a developed version of the prototype? How many workshops? I assume it is the same sample as in the telephone interviews and the focus group discussion.\nP. 17: Outputs: “The current study will yield a co-designed app and intervention program meticulously tailored to the needs of older adults, which will then be carried onto a randomised controlled trial (RCT) for further evaluation.” In the discussion, the authors state that the intervention will be pilot-tested as part of a final and third workstream (not included in the current protocol). “A pilot study is planned to evaluate the feasibility of the LightSPAN intervention before broader implementation.” I suggest replacing the “randomised controlled trial (RCT)” with “a pilot study evaluating the feasibility of the intervention”.\nP. 17: Outputs: “co-designed app and intervention program...” Some clarification is needed. Is not the intervention delivered as a mobile phone app? Or might I have missed any other intervention elements?\nP. 18: The authors can decide whether “co-design” is necessary. The conclusion (after deleting “co-design”) still reflects a user-centred approach and an empathic design approach.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "344589",
"date": "03 Jan 2025",
"name": "Kathryn Reid",
"expertise": [
"Reviewer Expertise Sleep and Circadian Science",
"Aging"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIncreasing evidence supports the role of light exposure patterns as a contributing factor to health. The protocol to develop the mHealth LightSPAN app as described has the potential to have a significant impact on the health of older adults. Overall, the rationale and approach are clear, although it would benefit from some additional details.\nIt would be useful to provide some examples of the type of approaches that the research team will build into the mHealth application. The authors mention that there are evidence-based recommendations for light exposure patterns but that there are no “practical recommendations” of how to achieve these. While it is clear that the proposed research aims to provide these practical recommendations, some potential examples would be beneficial to the reader.\n\nOn page 4 there is mention of the project “developing and testing an mHealth behaviour change intervention”, as described there is no testing of the application in the current proposal.\n\nIn addition, in the same paragraph (page 4) it sounds as if the application already exists see ”LightSPAN mHealth app, which tracks light exposure using a light sensor and employs various behaviour-change strategies to optimise light exposure patterns”. This makes it unclear whether the goal is to develop a new application or to optimize an existing application for older adults?\nWork stream 1a-1d as reported are clear and well structured.\nVery little information is provided for Workstream 2a, for example there is no description of how the community service providers will be selected, recruited and what characteristics they will have. For example, will they be physicians (what specialty general medicine, neurology etc.) nurses, and researchers will they be hospital based or from community clinics or a mix? Will they be exclusively from Singapore? What will be the number of providers interviewed. There are also no specifics provided on whether these interviews will be structured and what information will be collected and how this will be used to develop the LightSPAN mHealth application.\nWork stream 2b study sample selection, will prior use of mHealth or light treatment be an exclusion factor? There will be 20 older adults selected for participation. It would be useful to provide some information about whether the selection of participants will be balanced for any demographic characteristics, such as age, sex, socioeconomic status, education etc.\n\nAnother consideration is where will the participants be recruited from, specifically will they be from one or several of the Active Ageing Centre’s to enhance diversity or perspectives.\nThere is brief mention of the sample of 20 being split into 4 groups and individuals, how will this be achieved, is it random or based on location?\n\nWill the prototyping workshop include the same 20 participants as for telephone interview and focus groups?\nHow will attrition be handled if there is dropout between the telephone interview, focus groups and prototype workshop? What is the minimum number of participants to be included in each of these phases.\nWhat is the proposed timeline for the different phases of the study?\nThe authors propose moving from the proposed protocol phase of co-designing the mHealth application into a randomized control trial. An initial pilot trial for assessment of feasibility and acceptability would be advised. Also what would the outcomes of the proposed trial be, would it simply be optimized light exposure patterns?\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "344591",
"date": "28 Jan 2025",
"name": "Nicholas Meyer",
"expertise": [
"Reviewer Expertise Sleep and circadian rhythms",
"mealth."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe focus of the current protocol is around the co-design of an mHealth behaviour change intervention targeting light exposure in older adults. The authors have put a great deal of thought into the steps through which an acceptable intervention can be developed, incorporating co-production approaches and mHealth implementation theory. All of this seems excellent and I have no further comments on these aspects.\nAn mHealth intervention that is beautifully designed in terms of acceptability, usability and adherence, would nonetheless be of little utility if it didn’t lead to improvements in health outcomes. It is not so clear from this proposal which health outcomes the intervention is seeking to improve, other than those that will be identified in the literature review in workstream 1a. I therefore wonder if it would be helpful, at this early stage, if the authors put greater a priori consideration into the what problems the proposed intervention are seeking to solve, in what populations, and how this will ultimately be tested? Much of this proposal appropriately seeks to develop the intervention in a ‘bottom up’ manner, with end-user input, but first setting the broad parameters of the intervention in a ‘top-down’ fashion also seems important.\nFor example, it seems the intervention will be designed for non-clinical populations - i.e. healthy older adults without significant cognitive decline or psychiatric problems. Is the final light intervention intended to be used as a preventative tool for reducing risk of transition to clinical disorders such as mild cognitive impairment, dementia or mood disorder? Or will the goal of the intervention be to improve daily functioning such as positive mood, energy levels, physical activity, in non-clinical groups? These are important considerations, as it will help the participants in the co-design study to be better able to frame their recommendations.\nThis may be the topic of a separate protocol, however it may also be helpful to consider how the final intervention will be evaluated - in a cohort of healthy older adults, who will be followed up in a randomised-controlled study? Or at a population-level study, looking at broader health and wellbeing outcomes on a larger scale? Which outcome measures will be examined? Again, this speaks to whether the intervention is envisioned to be a tool for clinical populations and targeted disease prevention, or a wider population level intervention.\n\nI appreciate much of these points are implicit in the protocol, however making them more explicit may benefit the broader aims of the study.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1356
|
https://f1000research.com/articles/13-942/v1
|
20 Aug 24
|
{
"type": "Systematic Review",
"title": "University Dropout: A Systematic Review of the Main Determinant Factors",
"authors": [
"Raul Quincho Apumayta",
"Javier Carrillo Cayllahua",
"Abraham Ccencho Pari",
"Vilma Inga Choque",
"Juan Carlos Cárdenas Valverde",
"Delsio Huamán Ataypoma",
"Javier Carrillo Cayllahua",
"Abraham Ccencho Pari",
"Vilma Inga Choque",
"Juan Carlos Cárdenas Valverde",
"Delsio Huamán Ataypoma"
],
"abstract": "Introduction This research is a systematic review aimed at synthesizing scientific evidence on the causes of university dropout, focusing on the subcategories of vocational guidance, academic performance, socioeconomic status, and institutional aspects between 2020 and June 2024.\n\nMethods Only articles addressing university dropout were considered, analyzing dimensions such as vocational guidance, academic performance, socioeconomic status, and institutional aspects. Articles published in indexed scientific journals with double-blind, double-blind peer, or open reviews between 2020 and June 2024 were included. The main databases used were Scopus, Web of Science, and Google Scholar. To assess the risk of bias in qualitative studies, the criteria from the article “Validity criteria for qualitative research: three epistemological strands for the same purpose” were used. For quantitative studies, the criteria from the article “Evaluating survey research in articles published in Library Science journals” were followed. For mixed-method studies, both sets of criteria were combined.\n\nResults A total of 23 studies were included: 15 quantitative (65.22%), 3 qualitative (13.04%), and 5 mixed-method (21.74%). All studies (100%) addressed the subcategories of socioeconomic status and institutional aspects. Regarding the academic performance subcategory, 86% of the studies addressed it, while the vocational guidance subcategory was covered by 73.91% of the studies.\n\nConclusions Vocational guidance, academic performance, socioeconomic status, and institutional aspects are crucial for reducing university dropout. Providing adequate professional guidance, academic support, financial assistance, and strong institutional support is fundamental to improving student retention and academic success.",
"keywords": [
"University dropout",
"vocational guidance",
"academic performance",
"socioeconomic status",
"institutional aspect"
],
"content": "Introduction\n\nUniversity dropout is a multifaceted problem that affects both educational institutions and society at large. This phenomenon is influenced by several key factors. Inadequate vocational guidance can lead to poor career choices, resulting in a disconnection from studies and, ultimately, dropout. Providing proper career guidance before the start of studies allows for informed decisions, reducing the risk of dropout. Academic performance also plays a crucial role, as students with better grades are less likely to abandon their studies. However, academic performance alone is not sufficient to ensure retention if it is not addressed alongside other factors (Bernardo et al., 2017; Chalela-Naffah et al., 2020; Kim & Kim, 2018; Santos-Villalba et al., 2023; Schmidt et al., 2023).\n\nSocioeconomic status is another critical determinant, as financial difficulties can force students to abandon their studies to work or attend to family responsibilities. Finally, institutional aspects, such as satisfaction with study programs, integration into the academic environment, and institutional support, are fundamental for reducing dropout rates. An integrated approach that considers vocational guidance, academic performance, socioeconomic status, and institutional aspects is essential to effectively address university dropout (Chalela-Naffah et al., 2020; Kim & Kim, 2018; Schmidt et al., 2023). Additionally, other important reasons include lack of motivation, low self-esteem, and frustration (dos Santos et al., 2022; Garcés-Delgado et al., 2024; Garcés-Prettel et al., 2024).\n\nThe impact of university dropout extends to economic, personal, and institutional levels. Dropout leads to frustrated professionals, a lower intellectual and productive contribution to society, and economic costs for families and institutions. Additionally, dropout is associated with difficulties in adapting to university studies, personal and professional challenges, and a lack of emotional support (Garcés-Prettel et al., 2024).\n\nTo prevent university dropout, it is essential to constantly monitor academic performance and include formal academic reinforcement activities (Santos-Villalba et al., 2023). Educational policies should be designed with the realities and needs of students in mind, using innovative methodologies to increase motivation (Garcés-Prettel et al., 2024; Kim & Kim, 2018). Communication between university administration, faculty, and students is crucial in academic retention processes (Chalela-Naffah et al., 2020; Valencia-Arias et al., 2023).\n\nThe economic implications of university dropout are significant. Dropout represents a high percentage of public expenditure on higher education and has economic consequences for families and institutions (Santos-Villalba et al., 2023). Socioeconomic factors and the income score provided by the University Admission Exam are important variables influencing student dropout (Viloria et al., 2019). The cumulative effect of low admission scores and living far from family support results in a higher probability of dropout, highlighting the economic impact on students (Chalela-Naffah et al., 2020).\n\nLikewise, university dropout is influenced by a multitude of factors, including academic performance, economic difficulties, and dissatisfaction with the educational experience. The impact of dropout on students includes personal and professional challenges, while the economic implications are significant for both individuals and institutions. Strategies to prevent dropout involve constant monitoring of academic performance, designing educational policies aligned with student needs, and implementing interventions that provide support and motivation to at-risk students.\n\nAll the theoretical information addressed so far leads to the following question: What scientific evidence exists regarding the causes of university dropout related to vocational guidance, academic performance, socioeconomic status, and institutional aspects between 2020 and June 2024? The general objective is to systematize the scientific evidence on the causes of university dropout, focusing on the subcategories of vocational guidance, academic performance, socioeconomic status, and institutional aspects between 2020 and June 2024.\n\n\nMethods\n\nFor this research, the following eligibility criteria were taken into account, as well as the methodological details provided in the publication “PRISMA 2020 Declaration: an updated guide for the publication of systematic reviews” (Page et al., 2021):\n\nInternational studies published between 2020 and June 2024 were included, focusing on the factors of university dropout. The studies had to employ qualitative, quantitative, and mixed methodological approaches, presenting a standardized methodological design. Only articles addressing the category of university dropout were considered, analyzing at least two of the subcategories of vocational guidance, academic performance, socioeconomic status, and institutional aspects. The articles needed to be published in indexed scientific journals with double-blind, double-peer blind, or open reviews.\n\nStudies published outside the period from 2020 to June 2024, documents that were not research articles, and those that did not specifically focus on university dropout or did not consider at least 50% of the study subcategories were excluded. Studies with poor methodological design were also discarded (Table 1).\n\nThe main databases used were Scopus, Web of Science, and Google Scholar. The search was conducted over a period of approximately 60 days, concluding in May 2024. During this time, the reference lists of identified studies were thoroughly reviewed to ensure no relevant sources were omitted.\n\nDescriptors such as University Dropout, Vocational Guidance, Academic Performance, Socio-Economic Status, and Institutional Aspect were used. This strategy allowed for a wide range of studies to be covered and ensured a comprehensive and representative data collection of the existing literature on the subject under study (Table 3).\n\n\n\n• TITLE (university AND dropout) AND PUBYEAR > 2019 AND (LIMIT-TO (DOCTYPE, \"ar\") AND (LIMIT-TO (OA, \"all\")) = 104 Results\n\n• (TITLE (university AND dropout) AND TITLE (vocational AND guidance)) AND PUBYEAR > 2019 = 17 Results\n\n• (TITLE (university AND dropout) AND TITLE (academic AND performance)) AND PUBYEAR > 2019 07 = 36 Results\n\n• TITLE (university AND dropout) AND TITLE (socio-economic AND status)) AND PUBYEAR > 2019 = 9 Results\n\n• (TITLE (university AND dropout) AND TITLE (institutional AND aspect)) AND PUBYEAR > 2019 = 14 Results\n\nThe process to determine if a study met the inclusion criteria was conducted in several stages. Two review authors independently screened each record and publication, reviewing titles and abstracts for preliminary selection. They then evaluated the full texts of the selected studies to confirm their eligibility. In cases of discrepancies, critical discussions were held to reach a consensus. Screening and inclusion were done manually, without the use of automation tools, to ensure accuracy and consistency in the application of the inclusion and exclusion criteria (Figure 1).\n\nTwo independent reviewers collected data from each publication, including details such as the article title, reference, year, study categories, approach, type of research, population and sample, and instruments used. The reviewers verified the data through discussions to resolve discrepancies, ensuring accuracy and consistency. No automation tools were used in this process.\n\nData on university dropout were collected, focusing on the reasons and impact of dropout on students and institutions. Additionally, data were collected on participant characteristics (age, gender, socioeconomic level, and educational background) and intervention characteristics (type of programs or policies). Studies with incomplete, missing, or questionable information were excluded.\n\nTo assess the risk of bias in qualitative studies, the criteria from the article “Validity criteria for qualitative research: three epistemological strands for the same purpose” (Aráoz Cutipa & Pinto Tapia, 2021) were used, focusing on the credibility and transferability of the qualitative studies. For quantitative studies, the criteria from the article “Evaluating survey research in articles published in Library Science journals” (Salvador-Oliván et al., 2021) were followed, evaluating survey design and data analysis. For mixed-method studies, both approaches were combined. Two authors independently conducted the assessment, resolving discrepancies by consensus.\n\nTo determine the eligibility of studies for synthesis, the characteristics of each study were tabulated and compared with the predefined inclusion criteria. A matrix was used, which included the article title, reference, year of publication, categories and subcategories, as well as relevant methodological information.\n\n\nResults\n\nTable 2.2 in Extended data shows a total of 23 investigations, distributed as follows: 15 quantitative studies (65.22%), 3 qualitative studies (13.04%), and 5 mixed-method studies (21.74%). All studies (100%) addressed the subcategories of socioeconomic status and institutional aspect. The subcategory of academic performance was covered by 86% of the studies, while the subcategory of vocational guidance was addressed by 73.91% of the studies. The table also includes relevant general methodological information for each included study.\n\nWithin the issue of University Dropout, Vocational Guidance emerges as a determining factor in dropout rates. Various studies have indicated that the lack of adequate career guidance can lead students to make poor career choices, which often results in a disconnection from their studies and, ultimately, in dropout (Castro-Martínez & Machuca-Téllez, 2023; Santos-Villalba et al., 2023; Thies & Falk, 2024). Thus, providing adequate guidance on study programs and professional training before students begin their studies allows them to make informed decisions, thereby reducing the risk of dropout (Thies & Falk, 2024). Scientific evidence supports that vocational guidance not only helps students identify their interests and skills but also provides them with a clear vision of their future career paths, which can increase their motivation and commitment (Candelario Navarrete et al., 2024; Castro-Martínez & Machuca-Téllez, 2023; Schmidt et al., 2023).\n\nMany students abandon their studies upon realizing that the field they chose does not align with their personal interests or professional goals. This misalignment leads to a loss of motivation and can trigger identity and attachment crises (Félix Ibarra et al., 2023; Santos-Villalba et al., 2023). Additionally, the lack of clear vocational guidance can make students feel disconnected and ill-prepared for the job market, increasing uncertainty about their professional future (Candelario Navarrete et al., 2024; Garcés-Prettel et al., 2024).\n\nStudent motivation and interest in their study program significantly impact dropout rates. In this regard, students’ passion and commitment to their field of study are essential for preventing dropout (Llauró et al., 2023). Conversely, poor career choices are a significant cause of dropout. A study included in this review found that 51.2% of students reported choosing the wrong profession (Marte Espinal & Fabián V, 2021); therefore, the lack of adequate career guidance can also lead students to perceive their education as irrelevant to their future careers, resulting in early abandonment of their studies.\n\nA study comparing university dropout rates between Spain and Colombia found that students’ disconnection from their studies, due to a lack of guidance, results in higher dropout rates (Guerrero & Espejo, 2024). Other research indicates that insufficient vocational guidance can lead to a lack of commitment and, ultimately, to dropout (Garcés-Prettel et al., 2024; Valencia-Arias et al., 2023). Additionally, the impact of social integration and family background also influences both students’ commitment to their studies and their decisions to drop out (Lázaro Alvarez et al., 2020).\n\nAcademic Performance is also a critical and determining factor in university dropout. The studies included in this work show that students with higher grade point averages are at a lower risk of dropping out, both for native and international students; thus, it can be deduced that academic performance plays a crucial role in preventing dropout (Thies & Falk, 2024). However, even students with high grade point averages, when facing emotional problems, cultural disconnection, lack of motivation, or even the perception of academic content as too simple and easy, can exhibit high dropout rates even in highly selective study programs (Thomsen, 2022). This finding suggests that academic performance, although important, is not the only factor influencing student retention.\n\nAs previously mentioned, academic performance is not only related to grades but also to students’ self-concept in specific subjects. For example, a study found that self-concept in mathematics is positively related to academic achievement, which in turn reduces the likelihood of dropout (Geisler et al., 2023). Conversely, low academic performance can lead to a lack of commitment and, ultimately, to dropout, especially when students are not diagnosed in time or do not receive adequate academic support (Gonzales Lopez & Evaristo Chiyong, 2021).\n\nLikewise, academic integration, such as strong bonds with peers and institutional commitment, is associated with a lower likelihood of dropout. Students who feel integrated into their academic environment are less likely to abandon their studies (Wagner et al., 2024). However, when these students exhibit low academic performance, including learning difficulties and low grades, it becomes one of the main causes of student dropout. They may feel demotivated and decide to leave (Castro-Martínez & Machuca-Téllez, 2023; Garcés-Delgado et al., 2024).\n\nOn the other hand, traditional teaching methods that fail to engage students can lead to feelings of failure and the decision to drop out of university (Santos-Villalba et al., 2023). It is also worth considering study habits and the amount of time students dedicate to this activity; as is known, nonexistent, inadequate, and ineffective study habits are correlated with low academic performance, which in turn leads to higher student dropout rates (Candelario Navarrete et al., 2024; Llauró et al., 2023). This emphasizes the need and importance of including pedagogical techniques in study programs that foster engagement and active participation of students in their learning process. Otherwise, low academic performance, lack of understanding of content, and even failing exams could be causes of school dropout (Guerrero & Espejo, 2024; Kabashi et al., 2022).\n\nRegarding Socioeconomic Status, financial problems stand out as a significant cause of school dropout, as a better financial situation is related to a higher probability of academic success and a lower risk of dropout (Thies & Falk, 2024). In this context, economically disadvantaged students are about 15 percentage points more likely to drop out compared to their peers with better economic conditions, even after accounting for other factors such as grades in previous educational stages (Thomsen, 2022).\n\nMost of the studies included in this research suggest that economic difficulties are one of the main causes of school dropout. Under this premise, students often leave school due to financial constraints, the need to work, or family responsibilities (Candelario Navarrete et al., 2024; Gonzales Lopez & Evaristo Chiyong, 2021). This situation must be observed with caution because employment opportunities during the early years of study can distract students from their academic responsibilities, making it difficult for them to interact with their peers and professors, thereby increasing dropout rates (Kabashi et al., 2022). Therefore, factors such as financial pressures and the eventual need for some students to economically support their families are critical causes affecting student retention (Guerrero & Espejo, 2024).\n\nOn the other hand, the lack of technical and technological resources necessary for online learning also influences the decision to drop out. This situation gained significant momentum with the onset of the COVID-19 pandemic, where many students worldwide were forced to leave their studies for this reason (Pertegal-Felices et al., 2022). Additionally, students from lower socioeconomic backgrounds, especially those facing food insecurity, are also prone to dropping out. When these students face severe food insecurity, their likelihood of dropping out more than doubles, making these factors key contributors to increasing dropout rates (Wagner et al., 2024). Furthermore, limited access to scholarships and financial support also influences school dropout rates. Students from lower socioeconomic backgrounds or those who do not receive adequate financial support for their studies are at a higher risk of dropping out (Llauró et al., 2023; Marte Espinal & Fabián V, 2021).\n\nRegarding Institutional Aspects, satisfaction with study programs, integration into the academic environment, and the good reputation of the university are critical factors that reduce the likelihood of school dropout, especially among international students (Thies & Falk, 2024). In Denmark, for example, the lack of elite universities leads the most advantaged students to seek out specific prestigious programs, thereby increasing dropout rates. This is because social selectivity depends more on a specific study program than on the perception of any particular institution (Thomsen, 2022).\n\nAdditionally, the transition from regular basic education to higher education, as well as the nature of university programs (especially when they do not meet students’ expectations), can significantly influence dropout rates. For example, the difference in cognitive demands between school and university mathematics can lead to dissatisfaction and dropout (Geisler et al., 2023). Therefore, a positive transition to university life and effective tutoring actions can significantly reduce the likelihood of students dropping out (Llauró et al., 2023). Other institutional factors such as the quality of support services, modular design, and faculty guidance also have a significant impact on dropout rates. Effective institutional support and well-designed curricular experiences can help reduce dropout rates by keeping students engaged and supported (Gonzales Lopez & Evaristo Chiyong, 2021).\n\nSimilarly, educational institutions, especially those of higher education, must develop better resilience strategies and support networks to help students cope with emerging crises such as the COVID-19 pandemic (Pertegal-Felices et al., 2022). During this period, the lack of institutional adaptation, coupled with outdated technological infrastructures, spiked student dropout rates. Additionally, factors such as class duration and ineffective or inadequate student tutoring systems were associated with higher dropout rates, highlighting the need for better institutional support (Wagner et al., 2024).\n\nOn the other hand, inflexible curricula and insufficient academic advising can lead to school dropout, as students may feel unsupported and unable to balance their studies with other responsibilities (Castro-Martínez & Machuca-Téllez, 2023). The results of this review also indicate that the quality of education, the lack of commitment from educators, and outdated educational policies contribute to exacerbating dropout rates (Santos-Villalba et al., 2023).\n\nFinally, institutions that do not provide a conducive and engaging environment contribute to higher dropout rates (Guerrero & Espejo, 2024). Likewise, those with rigid or inflexible institutional policies can also lead students to abandon their studies (Candelario Navarrete et al., 2024; Félix Ibarra et al., 2023; Kabashi et al., 2022). Therefore, collaboration between directors, administrators, professors, and students is essential to effectively address the issue of university dropout (Galve-González et al., 2023; Garcés-Prettel et al., 2024; González Sanzana & Arce Secul, 2021; Valencia-Arias et al., 2023).\n\n\nConclusions\n\nVocational Guidance plays a crucial role in reducing university dropout rates. The contributions of these researchers demonstrate that providing adequate career guidance can help students make informed decisions, aligning their interests and abilities with their professional goals, which in turn increases their motivation and commitment to their studies.\n\nAcademic Performance is a crucial factor in preventing university dropout. Scientific evidence indicates that students with better grades have a lower risk of abandoning their studies. However, additional factors such as academic support, integration into the university community, and socioeconomic challenges also play a significant role. Addressing these areas through targeted interventions can improve student retention and reduce dropout rates.\n\nRegarding Socioeconomic Status, factors such as family socioeconomic level and economic pressure significantly influence dropout rates. Economic challenges are a common reason why students leave their studies. Research included in this investigation has shown that there is a correlation between financial aid and dropout rates, as students who receive financial assistance are less likely to abandon their studies, especially at the beginning of their university education.\n\nFinally, Institutional Aspects are fundamental in preventing university dropout. Factors such as the quality of support services, social and academic integration, and appropriate educational policies can significantly improve student retention. Scientific evidence suggests that a comprehensive strategy that includes strong institutional support and mentoring programs can reduce dropout rates and ensure students’ academic success.\n\nPROSPERO: ID: 565816, Title: University Dropout: A Systematic Review of the Main Determinant Factors.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nReporting guidelines\n\nZenodo: University dropout: A systematic review of the main determinant factors. https://doi.org/10.5281/zenodo.13117695 (Quincho Apumayta et al., 2024).\n\nThis project contains the following underlying data:\n\n• 01 PRISMA_2020_checklist.pdf\n\n• 02 Search strategies for all databases, and main results.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAráoz Cutipa RA, Pinto Tapia B: Validity criteria for qualitative research: three epistemological strands for the same purpose. Summa Psicológica UST. 2021; 18(1): 47–56. Publisher Full Text\n\nBarradas Arenas UD, Cocón Juárez JF: Learning tools as a means of support in the reduction of failure at the universitaria autonoma del carmen for the distance modality. Revista Iberoamericana Para La Investigación y El Desarrollo Educativo. 2022; 13(25): e419. Publisher Full Text\n\nBernardo A, Cervero A, Esteban M, et al.: Freshmen program withdrawal: Types and recommendations. Front. Psychol. 2017; 8: 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCandelario Navarrete F, Ávila Romero R, Juárez Olascoaga BG: Analysis of poverty as a factor in the dropout rate of university students in Mexico City from 2000 to 2022. Salud, Ciencia y Tecnología - Serie de Conferencias. 2024; 3: 738. Publisher Full Text\n\nCastrillón-Gómez OD, Sarache W, Ruiz-Herrera S: Prediction of main variables that lead to student dropout by using data mining techniques. Formacion Universitaria. 2020; 13(6): 217–228. Publisher Full Text\n\nCastro-Martínez JA, Machuca-Téllez G: University dropout in Latin America: An ecological perspective. Estudios Pedagógicos (Valdivia). 2023; 49(2): 87–108. Publisher Full Text\n\nChalela-Naffah S, Valencia-Arias A, Ruiz-Rojas GA, et al.: Psycho-social and familial factors influencing drop-out rates among university students in the context of developing countries. Revista Lasallista de Investigacion. 2020; 17(1): 103–115. Publisher Full Text\n\ndos Santos RSS , Ponti MA, da Hora Rodrigues KR : The Use of Digital Reports to Support the Visualization and Identification of University Dropout Data. Lecture Notes in Computer Science (Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). 2022; 13305. Publisher Full Text\n\nFélix Ibarra AV, Urrea Zazueta ML, López Leyva S: School dropout of university students in the career of Law and Social Sciences. Revista de Ciencias Sociales. 2023; XXIX(2): 242–254. Publisher Full Text\n\nGalve-González C, Bernardo AB, Castro-López A: Understanding the dynamics of college transitions between courses: Uncertainty associated with the decision to drop out studies among first and second year students. European Journal of Psychology of Education. 2023; 39: 959–978. Publisher Full Text\n\nGarcés-Delgado Y, Fernández-Esteban MI, Álvarez-Pérez PR, et al.: The process of adaptation to higher education studies and its relation to academic dropout. European Journal of Education. 2024; (e12650): 1–20. Publisher Full Text\n\nGarcés-Prettel M, De la Ossa-Robinson S, Arellano-Cartagena W, et al.: Return or Not to Return to In-Person Classes? Motivations and Fears that Influence University Dropout in Colombia in the Post-Pandemic Era. Salud Uninorte. 2024; 40(1): 52–68. Publisher Full Text\n\nGeisler S, Rach S, Rolka K: The relation between attitudes towards mathematics and dropout from university mathematics—the mediating role of satisfaction and achievement. Educational Studies in Mathematics. 2023; 112: 359–381. Publisher Full Text\n\nGonzales Lopez E, Evaristo Chiyong I: Academic Achievement and Dropout of University Students from a Course in Both an Online and Face-to-Face Modality. RIED-Revista Iberoamericana de Educacion a Distancia. 2021; 24(2): 189–202. Publisher Full Text\n\nGonzález Sanzana Á, Arce Secul R: Personal and access factors that affect the retention and dropout of pre-service teachers at a chilean university in an extreme geographic area. SOPHIA AUSTRAL. 2021; 27(1): 1–19. Publisher Full Text\n\nGuerrero SC, Espejo RL: Deserción universitaria: estudio comparativo entre Colombia y España desde la perspectiva de género. Formación Universitaria. 2024; 17(2): 101–112. Publisher Full Text\n\nHenriquez Cabezas N, Vargas Escobar D: Predictive models of academic achievement and dropout of first year students of a chilean public university. Revista de Estudios y Experiencias En Educación. 2022; 21(45): 299–316. Publisher Full Text\n\nHoyos Osorio JK, Daza Santacoloma G: Predictive Model to Identify College Students with High Dropout Rates. Revista Electronica de Investigacion Educativa. 2023; 25(e13): 1–10. Publisher Full Text\n\nKabashi Q, Shabani I, Caka N: Analysis of the Student Dropout Rate at the Faculty of Electrical and Computer Engineering of the University of Prishtina, Kosovo, from 2001 to 2015. IEEE Access. 2022; 10: 68126–68137. Publisher Full Text\n\nKim D, Kim S: Sustainable education: Analyzing the determinants of university student dropout by nonlinear panel data models. Sustainability. 2018; 10(4): 1–18. Publisher Full Text\n\nLázaro Alvarez N, Callejas Z, Griol D: Factors that affect student desertion in careers in Computer Engineering profile. Revista Fuentes. 2020; 22(1): 105–126. Publisher Full Text\n\nLlauró A, Fonseca D, Romero S, et al.: Identification and comparison of the main variables affecting early university dropout rates according to knowledge area and institution. Heliyon. 2023; 9(6): e17435. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarte Espinal R, Fabián VL: Determinants of university dropout: a case study in the Dominican Republic. Sapienza: Int. J. Interdiscip. Stud. 2021; 2(1): 255–268. Publisher Full Text\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas. Rev. Esp. Cardiol. 2021; 74(9): 790–799. PubMed Abstract | Publisher Full Text\n\nPertegal-Felices ML, Valdivieso-Salazar DA, Espín-León A, et al.: Resilience and Academic Dropout in Ecuadorian University Students during COVID-19. Sustainability. 2022; 14: 1–12. Publisher Full Text\n\nQuincho Apumayta R, Carrillo Cayllahua J, Ccencho Pari A, et al.: University dropout: A systematic review of the main determinant factors (Version 1). Zenodo. [Dataset]. 2024. Publisher Full Text\n\nSalvador-Oliván JA, Marco-Cuenca G, Arquero-Avilés R: Evaluating survey research in articles published in Library Science journals. Revista Espanola de Documentacion Cientifica. 2021; 44(2): 1–18. Publisher Full Text\n\nSantos-Villalba MJ, del Olmo A , Fernández MJ, et al.: Incident factors in Andalusian university dropout: A qualitative approach from the perspective of higher education students. Frontiers in Education. 2023; 7: 1–14. Publisher Full Text\n\nSchmidt BJ, Boero P, Méndez Vera JA: Factors influencing university dropouts: The case of a Chilean state university. Revista Portuguesa De Educação, 2023; 36(1): e23002. Publisher Full Text\n\nThies T, Falk S: Which Factors Drive Major Change and University Dropout? An Analysis on International Degree-Seeking Students at German Universities. Journal of International Students. 2024; 15(1): 326–346. Publisher Full Text\n\nThomsen JP: The social class gap in bachelor’s and master’s completion: university dropout in times of educational expansion. Higher Education. 2022; 83(5): 1021–1038. Publisher Full Text\n\nValencia-Arias A, Chalela S, Cadavid-Orrego M, et al.: University Dropout Model for Developing Countries: A Colombian Context Approach. Behavioral Sciences. 2023; 13(5): 1–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nViloria A, Garcia Padilla J, Vargas-Mercado C, et al.: Integration of Data Technology for Analyzing University Dropout. Procedia Computer Science. 2019; 155: 569–574. Publisher Full Text\n\nWagner F, Wagner RG, Makuapane LP, et al.: Mental distress, food insecurity and university student dropout during the COVID-19 pandemic in 2020: evidence from South Africa. Frontiers in Psychology. 2024; 15(February): 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZárate-Valderrama J, Bedregal-Alpaca N, Cornejo-Aparicio V: Classification models to recognize patterns of desertion in university students Joshua. Ingeniare. Revista Chilena de Ingeniería. 2021; 29(1): 168–177. Publisher Full Text"
}
|
[
{
"id": "317134",
"date": "12 Sep 2024",
"name": "Enaidy Reynosa Navarro",
"expertise": [
"Reviewer Expertise Education and Educational Quality",
"Quality Education",
"and Education Administration"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe rationale and objectives are clearly stated. This systematic review focuses on understanding the causes of university dropout, with an emphasis on vocational guidance, academic performance, socioeconomic status, and institutional factors during the period from 2020 to June 2024.\nThe review also provides sufficient details on the methods and analysis, enabling replication by other researchers. The inclusion criteria are clearly specified (studies published between 2020 and 2024, standardized methodological approaches), as well as the databases used (Scopus, Web of Science, Google Scholar) and the search strategy (using specific descriptors such as \"university dropout\" and related terms). Additionally, the study selection process is detailed, including independent review by two authors and manual data extraction to ensure accuracy. An interesting aspect is that, to assess the risk of bias in qualitative studies, the validity criteria for qualitative research proposed by experts (Aráoz Cutipa & Pinto Tapia, 2021) were used. For quantitative studies, the criteria proposed in the research “Assessment of Survey-Based Research in Articles Published in Library Science Journals” (Salvador-Oliván et al., 2021) were followed, evaluating survey design and data analysis. For mixed-method studies, both approaches were combined. All these steps ensure that the study can be effectively replicated.\nStatistical analysis was not conducted in this systematic review because, being based on the PRISMA protocol, its main focus was the collection, evaluation, and synthesis of existing studies, rather than a meta-analysis, which would require direct statistical analysis. The applied PRISMA protocol focused on ensuring transparency and comprehensiveness in the literature review through rigorous study selection, risk of bias assessment, and qualitative synthesis of findings, providing essential information for preventing university dropout.\nThe conclusions are clearly supported by the review's findings. The research demonstrated, through the analysis of 23 studies, that vocational guidance, academic performance, socioeconomic status, and institutional factors are critical determinants in university dropout. These conclusions reflect a coherent synthesis of the findings, highlighting the need to implement specific interventions in these areas. It is recommended that educational institutions strengthen these aspects, providing adequate vocational guidance and financial support to significantly reduce student dropout and improve academic retention.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
},
{
"id": "317129",
"date": "30 Sep 2024",
"name": "Nicole Caldichoury-Obando",
"expertise": [
"Reviewer Expertise Psychologist",
"Master's Degree in Education with a Mention in Educational Guidance. Neurosciences applied to education. Neurodevelopmental disorders and special education."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe objective of this article is to systematize the scientific evidence on the causes of university dropout, focusing on the subcategories of vocational orientation, academic performance, socioeconomic level, and institutional aspects between the years 2020-2024. Regarding the method, it is not clearly defined, but it is inferred that it is of the theoretical or bibliographic research type with primary sources of information, where scientific articles published in indexed journals were used. The main conclusions are related to the relevance of generating vocational guidance processes to reverse university dropout, along with considering early warnings regarding university academic performance, since it is considered a good predictor of the successful university trajectory, it is also necessary to be able to count on academic and financial support to achieve greater integration and adherence to university life. In general terms, the article is clear and consistent with respect to the title, objectives, base question and keywords. It has a structure that contributes to the achievement of the objective and the proposed results, where updated bibliographic sources are cited, reaching logical conclusions. However, certain methodological procedures must be clarified in order to be able to replicate the study and provide foundations for the relevance of the study. Below are the details and topics to be improved:\n1.- Title Strengths (S): Clear and precise. Limitation (L): As a suggestion add the years 2020-2024.\n2.- Summary S: It provides a synthesis of the causes of university dropout between 2020-2024 in categories and subcategories, informs the number of selected scientific articles. L: Clarify and state the scientific method used and the search techniques used.\n3.-Introduction S: Context and review with references to studies. They mention university dropout as a multifaceted problem in which several factors influence. Inadequate vocational guidance, low academic performance, along with socioeconomic level as critical determinants, are alluded to, in addition to institutional aspects such as the academic environment and institutional support, motivation, self-esteem and frustration are also included. The basic question and objective are clear. L: It is important to mention all the key factors of university dropout, accompanied by their respective citations, as part of the justification. Clearly explain why it is relevant to study university dropouts, providing figures such as the number of students affected, and/or the amount of money involved. School dropout vs. university dropout, only focus on a standard term, since they are different age ranges and it is confusing.\n4.- Methodology S: They declare a method with inclusion and exclusion criteria, in addition to the sources of information and the time spent, tables are provided with search strategies and data extraction. Regarding the synthesis method, they mention a data matrix with the inclusion criteria, title, reference, year of publication, categories, subcategories, and the method used. L: The method indicates the title of an article and its author (Page et al., 2021), but does not declare the method. After reviewing the cited article, it is clear that they are guided by PRISMA 2020 criteria, but it is necessary to declare it. Within the inclusion criteria, concerns arise regarding whether they considered articles only in Spanish, English or in all languages, the studies were carried out in public or private universities, with what number of students, and the results of the studies reviewed. Regarding the selection of the studies, where Table 1 is attached, they must mention these data, refer to the criteria on which they worked to clean the data. And mention how many articles were excluded and why. In the data extraction, they do not mention the results of the studies reviewed, which they refer to later in the results section. In a list of data, they declare them, but it is necessary to provide a table. Risk of bias assessment in individual studies, cites the title of 2 articles and their authors (Aráoz Cutipa & Pinto Tapia, 2021; Salvador-Oliván et al., 2021), it is considered pertinent to be precise and indicate the criteria. Regarding the synthesis method, they mention a data matrix, but how many subjects participated in the studies (quantitative and qualitative), what techniques they worked with, the gender of the participants, country, language, results.\n5.- Results S: Finally, they mention the selection of 23 studies (15 quantitative, 3 qualitative and 5 mixed) according to their search criteria, where all meet the categories of socioeconomic level and institutional aspect and 86% with academic performance and 73.91% with vocational orientation. Data are provided on other interesting components of these categorizations such as motivation, commitment, bonds with peers, self-concept, learning difficulties, study habits, teaching methods, technological resources, among others. L: Include the table with the data of the 23 studies reviewed in the declared criteria, including their results and conclusions.\n6.- Conclusion S: Importance of focusing on vocational guidance in order to avoid university dropout. Academic performance, socioeconomic level, and institutional aspects are linked as relevant elements to prevent university dropout. It has registries and protocols, as well as underlying data. L: Use the term dropout rather than abandonment for internal coherence, if they refer to the same thing, otherwise clarify it. What was the limitation of the study, indicate. The study was funded. There are or are not conflicts of interest.\n\nConclusion of the article: It has a logical structure that they develop, but they must improve the points indicated, completing and/or clarifying information, the delivery of tables with the data will help to clear doubts and will deliver value to their work for its replicability.\nApproval status: Approved with reservations. The article has sufficient merits for indexing, as explained, it is coherent in the topics it wishes to explore. However, certain adjustments are required to enhance what has been done.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-942
|
https://f1000research.com/articles/13-983/v1
|
30 Aug 24
|
{
"type": "Clinical Practice Article",
"title": "The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort",
"authors": [
"Ines Naceur",
"Amal Baya chatti",
"Maysam Jridi",
"Tayssir Ben Achour",
"Monia Smiti",
"Fatma Said",
"Ines Naceur",
"Amal Baya chatti",
"Tayssir Ben Achour",
"Monia Smiti",
"Fatma Said"
],
"abstract": "Background Idiopathic inflammatory myopathies (IIM) encompass a heterogenous group of auto-immune diseases. The identification of myositis specific antibodies (MSA) and their associations with distinct phenotypes has improved the categorization of these conditions.\n\nObjective The aim of this study was to describe and report the clinical and immunological characteristics of IIM among Tunisian patients.\n\nMethod A retrospective study conducted in the internal medicine department at the Rabta University Hospital Center over 22 years, including adult patients with IIM according to the American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria and Connors’ criteria for anti-synthetase syndrome (ASS). Inclusion body myositis and myositis associated with other conditions were excluded. Demographic, clinical, and immunological characteristics were analyzed and compared.\n\nResults Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). Muscular involvement was present in 88% of patients, affecting locomotor muscles (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) systems. Muscle weakness was primarily noted in the pelvic girdle (81%), scapular region (74%), axial muscles (20%), and distal muscles (5%). Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. Diffuse interstitial pneumonia (DIP) was present in 45% of patients, cutaneous involvement in 85%, and articular involvement in 48%. MSAs were detected in 52% of patients. Analysis revealed significantly higher frequencies of amyopathic forms, DIP, palmar hyperkeratosis, and articular involvement in the ASS group. The DM group exhibited higher frequencies of gastrointestinal signs, Gottron’s papules, heliotrope rash, photosensitive rashes, ulcerations, and skin necrosis. The NAM group had higher frequencies of gastrointestinal signs, myolysis, and lower frequencies of DIP and cutaneous involvement.\n\nConclusion Our findings corroborate previously established clinico-immunological associations reported in the literature underscoring the need for a combined clinico-serological approach in classifying IIM.",
"keywords": [
"Myositis",
"Polymyositis",
"Dermatomyositis",
"Anti-synthetase Syndrome",
"Antibodies",
"Diffuse Interstitial Pneumonia"
],
"content": "Introduction\n\nIdiopathic inflammatory myopathies (IIM) encompass a group of rare acquired autoimmune diseases, primarily characterized by muscular inflammation accompanied by varying degrees of motor weakness.1 Despite this shared foundation, IIM exhibit significant heterogeneity both clinically and histologically. Indeed, within IIM, various muscular phenotypes are observed, where muscular weakness can be limited or absent, reflecting different mechanisms of muscular damage.2 Furthermore, IIM can be associated with extra-muscular manifestations, including lung, heart, skin, gastrointestinal tract, and joint involvement,3 or with cancer, which also reflects diverse pathophysiological mechanisms.4 This clinical polymorphism, as well as the rarity of these pathologies, are challenging for physicians trying to identify homogeneous patient subgroups.5 This diversity is reflected in the multiple proposed classification criteria developed since 1975. At that time, the first attempt to categorize IIM was published by Peter and Bohan, dividing them into two historical subgroups: polymyositis (PM) and dermatomyositis (DM).6 Over time, the spectrum of these diseases has expanded from conditions primarily characterized by myositis to true systemic diseases.7 Simultaneously, the deep understanding of the pathophysiological mechanisms of IIM and notably the discovery of myositis specific antibodies (MSA) has contributed to identify new IIM entities, such as immune-mediated necrotizing myopathy (IMNM) and anti-synthetase syndrome (ASS). Consequently, this original classification has come under scrutiny,8 and subsequent classifications have been reshaped, with growing number of published criteria for the classification and/or diagnosis of IIM, including criteria for PM, DM, ASS and IMNM, though not completely able to conceal the heterogeneity within this group.7 The scientific literature continuously advances in understanding these diseases, particularly regarding the role of MSA and their relevance for patient classification.1 Nevertheless, few studies have focused on IIM in Tunisia, especially considering these recent developments. Hence, we conducted this study aiming to describe the characteristics of IIM in Tunisian patients.\n\n\nMethods\n\nWe conducted a retrospective study including patients diagnosed with IIM from December 2001 to August 2022 in the internal medicine department of the Rabta Hospital in Tunisia.\n\nIncluded patients had to fulfill the 2017 American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria for IIM (meaning patients who had the necessary minimum probability (55%) to be classified as having IIM9). Patients who met the ASS criteria, proposed by Connors et al,10 were also included in the study. Patients with juvenile dermatomyositis and inclusion body myositis (IBM) were excluded. Patients with IIM according to the ACR/EULAR classification were divided into three subgroups based on the classification tree: DM, PM, and amyopathic dermatomyositis (ADM) and patients who met the criteria of Connors et al were classified into the ASS subgroup. The data, collected from medical records, included demographic data, clinical findings, results of laboratory investigations, electromyography, muscle biopsy findings and the presence of classification criteria for IIM. In patients who had myositis in association with another connective tissue disease (CTD), the presence of classification criteria for systemic sclerosis, systemic lupus erythematosus or rheumatoid arthritis (RA) was recorded. IIM associated with cancer was considered when the patient met the criteria for IIM and was diagnosed with a histologically documented cancer. The indirect immunofluorescence assay (IIFA) on HEp-2 cells was used for detecting antinuclear antibodies (ANA). Patients were assessed for MSA and myositis-associated antibodies (MAA) with extractable nuclear antigens (ENA) and immunodot assay (EUROLINE Autoimmune Inflammatory Myopathies, EUROIMMUN). The panel of MSA assessed depended on the type of Kit available in the hospital laboratory. The search for anti-HMGCR antibodies was not conducted in any patient (not available in our Laboratory).\n\nWe analyzed the data using the Statistical Package for the Social Sciences (IBM SPSS Statistics) version 2611 Categorical variables are reported as numbers (percentages) and numerical variables as either mean ± standard deviation or median and interquartile range (IQR).\n\n\nResults\n\nThe study included 97 patients. The mean age at the time of IIM diagnosis was 48.4 ± 13.8 years, with a predominance in the age group between 41 and 60 years (51%). The study population consisted in 70 females (72%) and 27 males (28%), with a male-to-female gender ratio of 0.36.\n\nOur cohort was composed by referring to two sets of criteria proposed for the classification of IIM and for the diagnosis of AAS, respectively. The ACR/EULAR criteria allowed the inclusion and classification of 88% (64/97) of the patients in our cohort with IIM. DM was the most common entity (n=46; 47%), followed by PM (n=35; 36%) and ADM (n=4; 4%). Connors et al criteria allowed the inclusion and classification as ASS of 34% (33/97) of the patients, including those excluded by the ACR/EULAR classification (n=12; 12%). Noteworthy, a group of patients (n=21, 22%) fulfilled both sets of criteria, and their subgroups varied depending on the criteria used: ASS according to Connors, and DM (n=6), PM (n=14), and ADM (n=1) according to ACR/EULAR criteria.\n\nDiagnostic delay and initial manifestations\n\nThe median time between symptoms onset and IIM diagnosis was five months [IQR = 2-12], with a range from two weeks to 15 years. Muscular involvement was the most frequent revealing manifestation of IIM (40%). The clinical heterogeneity of IIM was shown by the diversity of extra-muscular initial manifestations: cutaneous (32%), joint (22%), pulmonary (19%), and general signs (5%).\n\nMuscular involvement was observed in 85 patients (88%). Amyopathic forms of IIM were exclusively reported in the ADM subgroup (2/4, 50%) and the ASS subgroup (11/33, 33%). The involvement of skeletal muscles was constant (n=85, 88%). The clinical and paraclinical features of muscular involvement are summarized in Table 1.\n\nCutaneous involvement\n\nCutaneous involvement, noted in 85% of patients, was the most common manifestation following muscle involvement, with 18 different cutaneous signs described. Skin manifestations, traditionally recognized as pathognomonic and characteristic of DM, were prevalent within the DM and ADM subgroup in our series, including heliotrope rash (88%), rash in sun-exposed areas (66%), Gottron’s papules (60%), manicure sign (32%), Gottron’s sign (24%), and psoriasiform erythematous-violaceous eruption (24%). Less frequently, other signs were described in DM and ADM patients such as cutaneous vasculitis (14%), calcinosis (10%), skin ulcers (10%), panniculitis (8%), and palmar papules (2%). Similarly, cutaneous involvement in ASS was frequent (91%) and diverse, with palmoplantar hyperkeratosis (52%) and Raynaud syndrome (36%) being predominant. Notably, pathognomonic, and characteristic DM signs were also observed among these patients: heliotrope rash (15%), Gottron’s papules (12%), periungual erythema (12%), shawl and V- sign (6%) and Gottron’s sign (3%). Nailfold capillaroscopy, performed on 21 IIM patients, was pathological in 95% of cases. Although non-specific microangiopathy was the most described aspect (13/21; 62%), scleroderma pattern defined by the presence of mega-capillaries, was observed in seven patients (33%).\n\nCardiac and pulmonary involvement\n\nCardiac involvement noted in 14 patients consisted in pericarditis (9%) and myocarditis (8%). It was diagnosed based on cardiac MRI or scintigraphy. Pulmonary involvement was found in 51% of IIM patients. Diffuse infiltrative lung disease (ILD) was the most common pulmonary manifestation (45%). ILD was mostly common among ADM patients (4/4; 100%) and ASS patients (28/33; 85%). The characteristics of cardiac and pulmonary involvement are summarized in Table 2.\n\nJoint involvement\n\nArticular manifestations were found in 48% of IIM patients. Inflammatory arthralgias were reported in 48% of patients and synovitis in 19% of patients. Joint involvement was most commonly polyarticular (68%). Radiological bone erosions were identified in three patients (6%), two of whom had associated RA.\n\nSerological profile\n\nAntinuclear antibody (ANA) testing, conducted on 92 patients, was positive in 79% of cases. Anti-extractable nuclear antigen antibodies (anti-ENA), assessed in 91 patients, were found in 50% of them. Myositis specific antibodies (MSA) were detected in 52% of cases, with a predominance of anti-synthetase antibodies (ASA). Among these patients, 8% had more than one MSA. MAA were found in 50 patients (52%). Patients’ immunological findings are summarized in Table 3.\n\nAssociated pathologies\n\nIIM was associated with another CTD in 23% of patients. CTDs were: systemic sclerosis (35%), Sjögren’s syndrome (35%), systemic lupus erythematosus (21%) and rheumatoid arthritis (7%).\n\nIIM was associated with neoplasia in 16 patients (17%), 12 of them classified as DM (12/46, 26%). Cancer diagnosis was established within three years of the IIM diagnosis in 75% of cases (12/16). It was prior to IIM diagnosis in two patients, with intervals of 1 and 5 months, respectively, concurrently during the neoplastic investigation conducted after IIM diagnosis in five patients and was made after IIM diagnosis in nine patients, with an average time interval of 39.4 months. Cancers were revealed by IIM in half of the patients, among whom seven had no initial clinical indicators. Reported neoplasia were colorectal cancer (n=4), breast cancer (n=4), lung cancer (n=2), malignant hemopathy (n=2), cervical, endometrial, nasopharyngeal and kidney cancer in one case each. Noted histological types were adenocarcinoma (n=12), squamous cell carcinoma (n=2), hepato-splenic T-cell lymphoma (n=1) and myelomonocytic leukemia (n=1).\n\n\nDiscussion\n\nOur cohort was composed by referring to two sets of criteria proposed for the classification of IIM and for the diagnosis of ASS, respectively. This choice was driven by the absence, to date, of classification criteria identifying all subgroups of IIM.\n\nIn line with our study, the female predominance in IIM is a consistent finding in various global studies,12 as well as in Tunisia.12 In a systematic literature review, the age at diagnosis was 55.1 ± 19.5 years, with an initial peak during childhood (juvenile DM) and a second peak in adulthood.12 In our cohort, the mean age at diagnosis was 48.4 ± 13.8 years. This difference could be explained by the exclusion of juvenile MI and IBM in our study. Given the rarity of IIM and the methodological heterogeneity evident in the various selection criteria used in studies, an accurate estimation of their frequency remains a challenge for researchers.13 The first literature review aiming to determine the global incidence and prevalence of IIM found an overall incidence of 7.98 cases per million people per year and a prevalence of 14 per 100,000 inhabitants. This review did not identify well-established geographical disparities, although the incidence of DM appeared to follow a latitudinal gradient, possibly explained by the immunomodulatory effects of ultraviolet rays.12 In Tunisia, the incidence and prevalence of IIM have not been determined, but they are among the least common systemic CTD. In accordance with our study, a significant predominance of DM compared to PM has been reported in Tunisian patients.14\n\nThe classification of IIM remains a subject of numerous discussions and debates.5 Historically, two entities were distinguished, by Peter and Bohan: DM and PM. These criteria included cutaneous and muscular signs, and by definition, the latter must be present for the classification of PM or DM.6 This straightforward classification was widely used. However, it had a major limitation: the two defined entities were heterogeneous. Initially, it did not allow the isolation of IBM.4 These criteria, provided a more detailed description but were based on expert opinions.15 While some researchers focused on histological findings and underlying pathological mechanisms, others described MSA.5 Since, many other classifications were proposed to define other entities based on the progress and the discovery of new antibodies or on immunohistochemical staining.16–19 The role of MSAs despite of the multitude of proposed criteria, most have been based on expert opinions, primarily relying on clinical and histological data, and do not encompass all subgroups of IIM.7 To address these shortcomings, a panel of experts was convened in 2004 to develop new criteria, culminating in the long-awaited ACR/EULAR classification.9 When compared to Peter and Bohan,6 Tanimo,16 Targoff,17 Dalakas,15 and ENMC criteria,18 Targoff’s performed slightly better. No other set showed both higher sensitivity and specificity simultaneously. Furthermore, they allowed for proper classification of IIM subgroups in most cases. Thus, this classification brought significant improvements to existing criteria by proposing criteria developed from a large population of patients with and without IIM and was validated in external cohorts. The ease of use and the availability of an online calculator are also major advantages.20 However, since the development project was launched in 2004, several MSA were unknown, or their detection tests were not accessible. Consequently, several items, such as muscle MRI data and most MSA outside of anti Jo-1, were not included.9 Therefore, this classification appears clinically oriented, limiting its performance in distinguishing IIM subgroups.21 Our study illustrated these shortcomings: Twelve patients who were classified as ASS according to Connors’ criteria were not included by the ACR/EULAR classification, due to the absence or insufficient manifestation of muscle-related symptoms and the presence of other ASA apart from anti-Jo-1. Additionally, among the 21 patients classified as ASS according to Connors’ criteria and acknowledged by the ACR/EULAR classification, their distribution spanned across other subgroups. These findings highlight the limitations of the ACR/EULAR classification in accurately capturing the full spectrum of cases, especially those involving patients with non-Jo-1 antibodies and less apparent muscle involvement. On the other hand, the Connors criteria,10 adopted in our study for ASS diagnosis, are based on expert opinions and may possibly rely excessively on ASA, which can lead to over diagnosing this condition, in the absence of standardized immunological tests.22\n\nIn traditional descriptions, IIM were recognized as diseases primarily affecting muscles. Muscular involvement was the common denominator in the majority of classifications, and its absence ruled out the diagnosis4. With the identification of new subgroups and the emergence of MSA, we have witnessed a paradigm shift in the spectrum of IIM, where muscular involvement can be limited or absent.2 It was the case of 12% of our patients, exclusively classified as ADM and AAS. This finding reflects the inclusion criteria adopted, namely the ACR/EULAR criteria that recognize ADM and Connors’ criteria that acknowledge ASS in the absence of clear muscular manifestations. Although distal muscles are traditionally spared in IIM apart from IBM,23 they were involved in 5% of our patients. A proximo-distal deficit affecting dorsiflexion of the feet and extensors of the fingers has been reported subsequently in advanced forms.24 The utility of Electromyography lies in its high sensitivity and specificity for diagnosing IIM as well as its capability to rule out differential diagnoses. In line with our study, a “myogenic” or “mixed” pattern is frequently described in electromyography recordings in IIM patients.25 Normal electromyogram tracing should not, however, rule out the diagnosis, depending on the number of explored muscles, the timing of the test, the experience of the performer, and any previous use of corticosteroids.25,26 Although IIM share histopathological features such as mononuclear cell infiltrates and areas of necrosis, certain abnormalities have been linked to distinct entities.27 In PM, muscle fiber alteration is mediated by cytotoxic cellular mechanisms. Histological examination typically reveals inflammatory cells surrounding, invading, and destroying fibers, resulting in infiltrates within fascicles. In DM, infiltrates are perivascular, in septa around fascicles, and less commonly endomysial.28 Consistent with these findings, infiltrates were predominantly perivascular and perifascicular in our DM patients, while they were predominantly intraparenchymal in our PM patients. This result is expected since the ACR/EULAR classification takes this contrast into account.9 In line with other studies, perifascicular atrophy, long considered pathognomonic for DM,29 has been described in ASS.30 Necrotic and regenerating muscle fibers were more frequent in PM patients, probably reflecting the prevalence of necrosis in patients with IMNM as the ACR/EULAR classification is unable to differentiate IMNM from PM. Necrosis, often with or without minimal inflammatory infiltrates, is characteristic of IMNM, reported in 93% of patients.31 For several years, muscle biopsy was considered as the “gold standard” for IIM diagnosis and served as a cornerstone for several classifications, particularly the ENMC classification.18 With the emergence of MSA, diagnostic algorithms are evolving in favor of non-invasive methods, and it is suggested that biopsies must be reserved for seronegative IIM cases.32\n\nCardiac involvement in IIM varies widely in studies, ranging from 6 to 75%, depending on the inclusion or not of asymptomatic forms in the selection criteria.33 Myocarditis, reported in around 30% of autopsy series, is the most frequently described histological abnormality.34 As it is often subclinical, it was less common in our cohort. Electrographic abnormalities are the most common subclinical signs, accounting for 30 to 80% of cardiac manifestations,35 with the most common being bundle branch blocks, in line with our results.36\n\nILD was reported in 45% of our patients. Its frequency in the literature varies between 20 and 86%, depending on the diagnostic methods and the sample sizes of the different subgroups of IIM included. Consistent with other studies, ILD most presented with dyspnea and dry cough. However, its presentation is highly variable, ranging from asymptomatic forms to acute respiratory failure.37 This latter presentation holds a diagnostic challenge as it can mimic infectious pneumonia. Therefore, it is advisable to investigate for myopathy in cases of acute ILD without obvious pathological context.38 Four distinct histological aspects have been described in lung biopsies: cellular and fibrosing NSIP, OP, UIP and diffuse alveolar damage (DAD) and seems to be correlated with radiological patterns.39 NSIP is the most commonly reported pattern, found in 59% of our patients with ILD is reported in 61% to 81% of cases.40 Thus, heterogeneity in ILD behavior is well established, and several clinical presentations associated with specific histological and evolving patterns have been discerned.41 Given the invasive nature of lung biopsy, not recommended in this context, high-resolution thoracic computed tomography is the modality of choice for diagnosing and classifying ILD into patterns as defined by the American Thoracic Society/European Respiratory Society.42 Given the correlation between histological and radiological aspects, the most common CT abnormalities are ground-glass opacities and linear reticulations, corresponding to the NSIP pattern, in line with our study.39\n\nSkin involvement in IIM is highly diverse. Cutaneous manifestations, crucial for DM diagnosis, have traditionally been categorized based on their diagnostic relevance and frequency into seven categories.43,44 Nailfold capillaroscopy, commonly used in SS patients, has been widely evaluated in IIM. Among CTDs, IIM exhibit the highest incidence of scleroderma-like pattern, second only to SS.45 Poikiloderma and periorbital/facial edema are considered compatible with DM.43 However, considered typical of DM, have been reported in our ASS patients, explaining their classification into the DM subgroup according to ACR/EULAR criteria. Palmar hyperkeratosis characteristic of ASS, is observed in 19 to 57% of cases.30 Similarly, although reported in two of our patients classified solely as DM, it was much more common in the ASS subgroup. Recently, hyperkeratotic lesions referred to as “hiker’s feet,” have been reported in both DM and ASS.30\n\nJoint involvement noted in 48% of our patients are reported in 18% to 53% of IIM patients.46 These disparities can be explained by different definitions (arthralgia vs. arthritis) and varying inclusion criteria, impacting the composition of included subgroups, especially that of ASS. Although joint involvement is observed across other subgroups, it is more common in ASS.46 Consistent with the literature, polyarticular involvement was predominant (68%). Joint involvement is mild and rarely erosive.47\n\nWhile IIF on HEp-2 cells to detect ANA is a standard screening method for CTD, its applicability in the context of myositis is debatable. It is not sufficiently sensitive to detect all ASA, as indicated by recommendations from the International Union of Immunological Societies and the European Autoimmunity Standardization Initiative.48 This lack of sensitivity is reflected in negative ANA results in 24% of our patients. Furthermore, there is no consensus regarding whether to consider antibodies directed against cytoplasmic components of HEp-2 cells as positive ANA, despite cytoplasmic staining enhancing ASA sensitivity. Moreover, even in cases of positive ANA, the commonly used algorithm for additional tests typically includes only anti-Jo-1 antibodies. Therefore, a multi-specific immunodetection assay is the recommended immunological test when suspecting myositis. Nevertheless, IFI remains valuable for several reasons. First, it remains the reference method in the frequent situation of overlap with CTD, especially SS. Additionally, since several MSA exhibit distinctive nuclear or cytoplasmic IFI patterns, it can add specificity to a positive result obtained through immunodetection by confirming a pattern consistent with the MSA in question.49 Although these IFI aspects are not specific for most MSA, this added value has been demonstrated for anti-SRP antibodies.50 Lastly, some myositis patients have positive ANA in IFI without any of the currently known MSA, suggesting that several antibodies have not yet been identified.49\n\nMore than 20 autoantibodies have been identified in patients with myositis, conventionally classified into Myositis Specific Antibodies (MSA) and Myositis Associated Antibodies (MAA), the latter referring to autoantibodies that can also be found in other CTDs. Interestingly, detecting multiple MSAs in the same patient is extremely rare, making them ideal biomarkers to identify homogeneous subsets of myositis.51\n\nCancer was diagnosed in 17% of our patients, most commonly during DM, in line with existing literature. The frequency of cancer in IIM varies widely between 3 and 63%.52,53 DM has the highest increased risk, with a standardized incidence ratio ranging from 2.2 to 7.7 according to studies. Cancer can precede, accompany, or follow the diagnosis of IIM, but most cases occur concurrently or within a year of IIM diagnosis.54 Although it gradually decreases, the standardized incidence ratio remains elevated for several years.55 In an Australian study, it did not return to that of the general population even after 16 years of follow-up.56 Due to this temporal proximity, the term “Cancer Associated Myositis (CAM)” has been coined to define cancers diagnosed within three years of IIM diagnosis.54 This was the case for three-quarters of our patients. Consistent with the literature,57 adenocarcinoma was the most frequent histological type in our study. Lung, digestive, ovarian, breast, cervical, bladder, prostate cancers, as well as Hodgkin lymphomas, are among the most frequently associated cancers54 with varied frequencies, generally reflecting those observed in the matched general populations based on demographic characteristics.55\n\n\nConclusion\n\nIIM are a heterogeneous group of inflammatory disorders affecting muscle with systemic involvement. Many classifications are proposed but none is exhaustive. Actually, the most used classifications are based on serological testing which contribute which contributes to the identification of the type IIM, its clinical phenotype and the association with other pathologies in particular neoplasia.\n\n\nConsent\n\nWritten informed consents for publication of their clinical details were obtained from the patients.",
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Publisher Full Text\n\nVuillard C, Pineton de Chambrun M, de Prost N , et al.: Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study. Ann. Intensive Care. 2018 Dec; 8(1): 87. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMimori T, Nakashima R, Hosono Y: Interstitial lung disease in myositis: Clinical subsets, biomarkers, and treatment. Curr. Rheumatol. Rep. 2012 Jun; 14(3): 264–274. PubMed Abstract | Publisher Full Text\n\nHallowell RW, Paik JJ: Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management. Clin. Exp. Rheumatol. 2022 Feb 25; 40(2): 373–383. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPalmucci S, Di Mari A, Cancemi G, et al.: Clinical and radiological features of interstitial lung diseases associated with polymyositis and dermatomyositis. Medicina (Kaunas). 2022 Nov 30; 58(12): 1757. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTravis WD, Costabel U, Hansell DM, et al.: An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013 Sep 15; 188(6): 733–748. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMainetti C, Terziroli Beretta-Piccoli B, Selmi C: Cutaneous manifestations of dermatomyositis: a comprehensive review. Clin. Rev. Allergy Immunol. 2017 Dec; 53(3): 337–356. PubMed Abstract | Publisher Full Text\n\nDeWane ME, Waldman R, Lu J: Dermatomyositis: clinical features and pathogenesis. J. Am. Acad. Dermatol. 2020 Feb; 82(2): 267–281. Publisher Full Text\n\nZanframundo G, Tripoli A, Cometi L, et al.: One year in review 2020: idiopathic inflammatory myopathies. Clin. Exp. Rheumatol. 2021 Feb 5; 39(1): 1–12. PubMed Abstract | Publisher Full Text\n\nKlein M, Mann H, Vencovský J: Arthritis in idiopathic inflammatory myopathies. Curr. Rheumatol. Rep. 2019 Dec; 21(12): 70. Publisher Full Text\n\nKlein M, Mann H, Pleštilová L, et al.: Arthritis in idiopathic inflammatory myopathy: clinical features and autoantibody associations. J. Rheumatol. 2014 Jun; 41(6): 1133–1139. Publisher Full Text\n\nAgmon-Levin N, Damoiseaux J, Kallenberg C, et al.: International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann. Rheum. Dis. 2014 Jan 1; 73(1): 17–23. PubMed Abstract | Publisher Full Text\n\nDamoiseaux J, Vulsteke JB, Tseng CW, et al.: Autoantibodies in idiopathic inflammatory myopathies: clinical associations and laboratory evaluation by mono- and multispecific immunoassays. Autoimmun. Rev. 2019 Mar; 18(3): 293–305. PubMed Abstract | Publisher Full Text\n\nBossuyt X, Fieuws S: Detection of antinuclear antibodies: added value of solid phase assay? Ann. Rheum. Dis. 2014 Mar; 73(3): e10–e10. PubMed Abstract | Publisher Full Text\n\nMcHugh NJ, Tansley SL: Autoantibodies in myositis. Nat. Rev. Rheumatol. 2018 May; 14(5): 290–302. Publisher Full Text\n\nMustafa KN, Dahbour SS: Clinical characteristics and outcomes of patients with idiopathic inflammatory myopathies from Jordan 1996–2009. Clin. Rheumatol. 2010 Dec; 29(12): 1381–1385. PubMed Abstract | Publisher Full Text\n\nBaron M, Small P: Polymyositis/dermatomyositis: clinical features and outcome in 22 patients. J. Rheumatol. 1985 Apr; 12(2): 283–286. PubMed Abstract\n\nOpinc AH, Makowska JS: Update on malignancy in myositis—well-established association with unmet needs. Biomolecules. 2022 Jan 11; 12(1): 111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUngprasert P, Bethina N, Jones C: Malignancy and idiopathic inflammatory myopathies. North Am. J. Med. Sci. 2013; 5(10): 569–572. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLimaye V, Luke C, Tucker G, et al.: The incidence and associations of malignancy in a large cohort of patients with biopsy-determined idiopathic inflammatory myositis. Rheumatol. Int. 2013 Apr; 33(4): 965–971. PubMed Abstract | Publisher Full Text\n\nHill CL, Zhang Y, Sigurgeirsson B, et al.: Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 2001 Jan; 357(9250): 96–100. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "323540",
"date": "09 Oct 2024",
"name": "Rille Pullerits",
"expertise": [
"Reviewer Expertise Rheumatology and Clinical Immunology."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this article, the authors have retrospectively summarized the clinical and immunological characteristics of Tunisian patients with idiopathic inflammatory myopathies (IIM) over two decades at the Rabta University Hospital. The study has a clear rationale and is important, since not many studies are published regarding IIM in this geographical area. Although the study seems well written and well summarized, the manuscript can be further improved.\nMajor points:\nThe Methods section is very vaguely described. How were the patients identified? From medical records using ICD-10 diagnostic codes? From registry data? According to the description, only patients with probable IIM (probability >55%) and with definite IIM (probability >90) as scored by 2017 EULAR/ACR classification criteria were included. How many patients had possible IIM (probability between >50% and <55%) and were still treated in the clinic as IIM? I miss the flowchart about inclusion i.e. how many patients were identified and how many included/excluded. The inclusion/exclusion criteria should be better described.\nIn patients who had IIM in association with another CTD, please specify the classification criteria used for those diseases (SLE, systemic sclerosis, Sjögrens syndrome and RA). For all these diseases, there are different sets of classification criteria available. Which ones were used?\nOne of the objectives of the study was to describe and report the immunological characteristics of IIM. However, the immunological methods are not described in sufficient details. Which Hep-2 cells and equipment for evaluation were used? What was the cut-off for ANA positivity? Which Autoimmunity Inflammatory Myopathies Profiles were used? Dotblot? Lineblot? How was the cut-off defined? The authors write “The panel of MSA assessed depended on the type of Kit available in the hospital laboratory”. Since the study period covers 22 years, different sets of Euroimmun assays have been available during this period and the number of available antigens on lineblot has been increased over time. Please specify which assays were used to make it clear for reader.\nAlso, please describe which methods were used to detect ENA? Which antibodies are included in the ENA-panel you have used? The more appropriate term to use is \"ANA specificity\" rather than \"ENA\". ENA is still used in some contexts, particularly when referring to the classic panel of autoantibodies (Ro, La, Sm, RNP, Scl-70, Jo1), the term \"ANA specificity\" is generally more accurate and comprehensive for describing the range of autoantibodies tested in modern clinical practice.\nDistribution according to classification criteria – it would be illustrative and better for the readers to understand if the authors use Venn diagram to indicate the classification criteria and the overlap of the criteria.\nCardiac and pulmonary involvement. How was pulmonary involvement defined? How was cardiac involvement defined? I do not agree with authors that aspiration pneumonia is pulmonary involvement of idiopathic inflammatory myopathy. Aspiration pneumonia cannot usually be classified as a direct pulmonary involvement of IIM. It is rather an indirect (secondary) complication related to the disease due to swallowing difficulties (weakness of the pharyngeal and esophageal muscles) or due to respiratory muscle weakness.\nSerological profile. The detection of multiple MSA in a single patient appears to be relatively uncommon, most of the patients usually have a sole antibody specificity. In your cohort, 8% had more than one MSA. Please specify the coexistence of the antibodies.\nDiscussion. The authors should also acknowledge the limitations of their study.\nMinor points:\nDefine NAM in the abstract. Keep consistency throughout the manuscript. In the discussion section, IFI is used instead of IIF.\n\nIs the background of the cases’ history and progression described in sufficient detail? No\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the conclusion balanced and justified on the basis of the findings? Yes",
"responses": []
},
{
"id": "323537",
"date": "31 Oct 2024",
"name": "Helene Alexanderson",
"expertise": [
"Reviewer Expertise Idiopathic inflammatory myopathies",
"clinical and molecular effects of exercise",
"development of objective and patient-reported outcome measures",
"registry-cohort studies"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript sets out to describe a large cohort of patients with IIM in Tunisia with focus on clinical presentation, antibodies and classification. This is a well-written manuscript that provides new information about IIM patients in Tunisia.\nBelow are my comments and questions.\n1. I Believe that patient organizations around the world are objecting to the abbreviation for antisynthetase syndrome ASS, and that the IIM expert community is leaning towards ASSD.\n2. In methods, it is not quit clear that patients with JDM or IBM were excluded. I suggest to include a flow chart describing how many patients were in the cohort in total and how many were excluded from analysis and why.\n3. Please include information on assessments of pharyngeal-esophagus muscles, larynx muscles, breathing muscles, dysphagia, dysphonia, myalgia, and the MRC scale. Were muscles assessed bilaterally, neck flexion/extension?\n\n4. How was AMD defined? 5/5 on MRC? I suggest a discussion on measures used in this study relation to the International Myositis Assessment and Clinical Studies Group consensus measures for disease activity and also other tools available to assess muscle impairment. For example, the Manual Muscle test 8 or 15 muscle groups. The Functional Index 2 and 3 are emerging as IIM-specific and valid tools more sensitive to detect muscle weakness compared to MMT or MRC, Further, other functional tests such as the Timed-Stands test are also proven feasible, objective and standardized. CK-levels and other liver enzymes hare not considered as relevant assessments of disease activity, but rather the Myositis Disease Activity Assessment Tool (MDAAT) including the 6-item core set of disease activity measures are recommended.\n5. have you collected any patient-reported outcomes such as physical function or quality of life, pain or fatigue? I see that myalgia was assessed, how? This would enrich the results, to also describe patients' lived experience of myositis in Tunisia compared to other countries.\n6. Discussion: Last rows on page 8. There are studies providing objective assessments of distal muscle weakness in non-IBM IIM patients.\n-Josefson A et al, 1996 [Ref 1]\n-Alexanderson H et al, 2006 [Ref 2]\n-Regardt M et al, 2011 [Ref 3]\n\n7. Please discuss possible limitations of the study. Are there missing data, variations in assessment tools or definitions of symptoms or comorbidities during the time of data collection?\n8. Conclusions. Please suggest future perspectives and/or clinical implications.\nMinor issues. Abstract. Please write out the abbreviation NAM Conclusion in manuscript: Which contributes are written twice Discussion: In what way did the Targeoff classifications perform better?\n\nIs the background of the cases’ history and progression described in sufficient detail? No\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the conclusion balanced and justified on the basis of the findings? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-983
|
https://f1000research.com/articles/13-1355/v1
|
12 Nov 24
|
{
"type": "Research Article",
"title": "Understanding the future of dengue in Malaysia: Assessing knowledge, attitude, and homeowner practices in mitigating climate-driven risks",
"authors": [
"Jo Ann Andoy-Galvan",
"Sapna Shridhar Patil",
"Yin How Wong",
"Priya Madhavan",
"Lei Hum Wee",
"Pei Pei Chong",
"Chung Yeng Looi",
"Imam Shaik",
"Anitha Ponnupillai",
"Ameya Ashok Hasamnis",
"Prabal Bhargava",
"Arasarethinam Mugilarasi",
"Eng Hwa Wong",
"Chai Hong Yeong",
"Weng Keong Yau",
"Mahalingam Dinesh",
"Kulankara Balan Venugopalan",
"Nor Asiah Muhamad",
"Nur Hasnah Ma’amor",
"Izzah Athirah Rosli",
"Fatin Norhasny Leman",
"Sapna Shridhar Patil",
"Yin How Wong",
"Priya Madhavan",
"Lei Hum Wee",
"Pei Pei Chong",
"Chung Yeng Looi",
"Imam Shaik",
"Anitha Ponnupillai",
"Ameya Ashok Hasamnis",
"Prabal Bhargava",
"Arasarethinam Mugilarasi",
"Eng Hwa Wong",
"Chai Hong Yeong",
"Weng Keong Yau",
"Mahalingam Dinesh",
"Kulankara Balan Venugopalan",
"Nor Asiah Muhamad",
"Nur Hasnah Ma’amor",
"Izzah Athirah Rosli",
"Fatin Norhasny Leman"
],
"abstract": "Introduction Dengue fever poses a significant public health threat, particularly in tropical regions like Malaysia. The rising incidence of dengue outbreaks challenges healthcare systems and highlights the urgent need for effective preventive measures. Climate change, with rising temperatures and shifting rainfall patterns, is expected to worsen the dengue situation in the coming years.\n\nMethods . This is a cross-sectional study conducted among adult residents of low-cost housing apartments in an urban poor community in Kuala Lumpur, Malaysia involving approximately 16,000 residents. A representative sample of 1,636 residents was calculated using the Krejcie and Morgan formula, and stratified random sampling was used to ensure proportional representation across the various floors of each PPR community apartment block. Data were collected using a structured questionnaire adapted from a validated Malay version. The questionnaire assessed respondents’ knowledge, attitudes, and practices (KAP) related to dengue prevention, categorising KAP scores as “Good” (≥80%) or “Poor” (<80%). Descriptive statistics summarized population characteristics and KAP scores, while logistic regression identified predictors of KAP levels, with significance set at p ≤ 0.05.\n\nResults In this community, 76.7% of participants exhibited poor knowledge and 83.1% had a negative attitude towards dengue, despite 66.7% demonstrating good preventive practices. The PPR location significantly predicts dengue knowledge, attitudes, and preventive practices, with p-values of less than 0.001 for all domains. Marital status also predicts dengue knowledge (p = 0.007) and preventive practices (p = 0.023), while prior infection with dengue is a predictor of preventive practices (p = 0.047).\n\nConclusion Despite the community’s good dengue prevention practices, likely influenced by environmental expectations, there remains a critical need for education to sustain and strengthen these efforts, as climate change continues to worsen in the coming years. It is crucial to help residents grasp the relevance of these practices, so they can apply them more effectively as climate-driven risks intensify. Targeted interventions should de designed differently for each of the four PPR communities as their levels of knowledge, attitude and practices vary significantly, taking into account independent factors like marital status and prior dengue infection, which shape preventive behaviors.",
"keywords": [
"Keywords: dengue",
"knowledge",
"attitude",
"practices",
"PPR"
],
"content": "Introduction\n\nClimate change has emerged as a pressing global issue, with extensive consequences on environmental, social, and public health aspects. The increasing intensity of extreme weather conditions, rising temperatures, and shifting precipitation patterns are exacerbating existing challenges leading to a range of adverse health outcomes, including the spread of vector-borne diseases. These diseases are particularly susceptible to the impacts of climate change due to alterations in vector habitats and disease transmission dynamics. The modified environment creates favourable conditions for vector proliferation and disease transmission, leading to increased incidence and geographic spread of these diseases (Vieira et al., 2024).\n\nMalaria and Dengue fever are among the most prevalent vector-borne diseases worldwide, with an estimated incidence of 249 million cases of Malaria (WHO, 2023) and 100-400 million cases of Dengue in 2022 (WHO, 2024). Warmer temperatures are expanding the geographic range of mosquitoes responsible for transmitting malaria (Anopheles) and dengue (Aedes). Cases are now being reported more frequently in countries with cooler climates, where they were rarely reported previously (Lenharo, 2023). Heavy rainfall and flooding create conducive environments for mosquito breeding. Stagnant water pools formed during floods serve as their ideal breeding.\n\nMalaysia has entered the elimination phase of malaria control, but Dengue fever remains a growing problem (Sa-Ngamuang et al., 2023; Md Taib & Atil, 2023). Dengue fever is a prominent public health challenge which often affects the tropics. It is brought upon by the flavivirus transmitted by the Aedes aegypti mosquito. In Malaysia, despite various control measures, the incidence of dengue continues to rise, (Chem et al., 2024), with a 235.6% increase in cases reported between December 31, 2022, and June 10, 2024 (Tan & Gerard, 2024). A retrospective study conducted by Bujang et al. aimed to investigate the trend in dengue cases in Malaysia revealed a staggering 1561.3% increase from 1995 to 2014. The study also reported an incidence rate of 161.5 per 100,000 population in 2010 and is projected to rise to 940.0 per 100,000 population by 2040 (Bujang et al., 2017).\n\nAs of May 10, 2024, a total of 56,884 dengue cases have been reported, covering the period from December 31 of the previous year up to the present day. The daily average for new cases stands at 334 (see Table 1). From 2022 to 2024 (accumulated cases from January to May), there was a substantial increase of 315.23% in dengue cases (Wan-Fei et al., 2023) (See Figure 1). Similarly, from 2023 to 2024 (accumulated cases from January to May), there was a notable increase of 124.20% in dengue cases (Ministry of Health Malaysia 2023).\n\n* Source from iDengue_Versi 3.0. (May 10, 2024). Retrieved from https://idengue.mysa.gov.my/.\n\nSource from National Crisis Preparedness and Response Centre (CPRC), Ministry of Health Malaysia (MOH).\n\nStates like Selangor, with densely populated urban areas, report the highest incidence rates, exacerbated by poor housing conditions that contribute to mosquito proliferation. The steep rise in dengue cases can be attributed not only to environmental factors but also to the limitations of current prevention measures. PKD in Selangor is grappling with a substantial burden as the region contends with a surge in dengue cases. As of May 12, 2024, 29,678 cases have been reported, accompanied by the identification of 124 hotspot areas (idengue.mysa.gov.my, 2024).\n\nPKD employs several commendable initiatives in managing the dengue situation in their locality (Rusli et al., 2022), encompassing early detection facilitated by the integrated reporting system through e-notifikasi, strict enforcement of reporting protocols, and targeted destruction of breeding sites. Doctors are mandated to report dengue cases within 24 hours under the “Act 342 Prevention and Control of Infectious Diseases Act 1988,” with non-compliance incurring a fine of RM 1000. Once a case is reported, the PKD registers reported cases to assess outbreak potential, defined as two cases in a locality or one case residing 200 meters from the index case or first case within 14 days.\n\nIn response to outbreaks, the PKD conducts fogging and search-and-destroy operations. Health officers will conduct fogging within a 400-meter radius from the reported outbreak’s address, repeating these cycles every 5-7 days which continues for 2 weeks after the outbreak. They also identify breeding sites, with RM 500 penalties for house owners where breeding sites were identified. Larviciding activities are initiated and repeated every 3-5 days until 2 weeks after the resolution of the outbreak.\n\nHowever, if these areas continue to have reported cases after 30 days, they will be considered as Dengue Hotspots and will be published on the “idengue” website. PKD will work closely with these communities, by meeting them weekly for weekly presentation of cases and education. The State Health Department or the Jabatan Kesihatan Negeri (JKN) will also encourage the community to do clean-up drives or the “Gotong Royong” in Malay ( Figure 2).\n\nPKD = Pejabat Kesihatan Daerah (District Health Office), E-notifikasi = online notification system used for reporting certain communicable diseases, JKN = Jabatan Kesihatan Negeri (State Health Department).\n\nSource: Pelan Strategik Pencegahan Dan Kawalan Denggi Kebangsaan 2022-2026.\n\nEnvironmental factors are key determinants in the proliferation of dengue vectors and the subsequent outbreak of the disease. Poor waste management practices, including irregular garbage collection and improper disposal of waste, contribute significantly to the breeding of mosquitoes. In urban areas, where population density is high, and infrastructure may be inadequate, stagnant water in discarded containers, blocked drains, and neglected water storage vessels become ideal breeding sites for Aedes mosquitoes.\n\nCollaborative efforts between government agencies, local authorities, community organisations, and residents are essential to creating sustainable solutions that mitigate the environmental factors contributing to dengue outbreaks.\n\nThe strain on resources is palpable, with the PKD stretched thin in its efforts to combat the escalating dengue crisis. Hotspot areas, identified as focal points of dengue transmission, continue to report cases over extended periods, indicating persistent challenges in eradication efforts. Compounding these challenges is the overwhelming caseload experienced during massive outbreaks, leading to lapses in essential activities like active case detection and comprehensive environmental risk assessments (Tee et al., 2019).\n\nThis scenario underscores the urgent need for bolstered resources, strategic interventions, and enhanced collaboration between stakeholders to effectively address the dengue epidemic in Selangor. Without concerted efforts to strengthen the capacity of the PKD and implement targeted measures to curb dengue transmission, the region may continue to face prolonged and severe public health challenges associated with the disease.\n\nThe government has invested significant resources in vector control efforts and imposed fines for failing to eliminate mosquito breeding grounds. However, many of these breeding sites are located within private homes, where government interventions are limited. The real issue lies deeper: at the heart of the problem are the residents’ practices regarding dengue prevention. Effective prevention starts with homeowners taking responsibility for eliminating potential breeding grounds on their properties. But for these practices to be adopted, residents must first recognize their importance. This requires not only knowledge about dengue prevention but also a shift in attitude. Residents must perceive their susceptibility to infection and understand the severity of the disease and its impact on their families and daily lives. Only when they fully grasp these risks can they embrace preventive measures and protect their communities from dengue.\n\nA study by Zaki et al. involving 847 residents in a Selangor district, reported that the majority have a good understanding of dengue fever (97.1%) and its correlation with climate factors (90.6%). A significant percentage expressed willingness to contribute to reducing dengue cases in their locality (91.5%). However, over half of the respondents (64%) do not regularly inspect potential hotspots in their area, and not everyone is eager to participate in cleanup initiatives (Zaki et al., 2019). Correct understanding or knowledge does not necessarily result in the adoption of correct attitudes and practices for dengue prevention A scoping review done by Rahman et al., on identifying the barriers to knowledge, attitude and practices of dengue prevention in the community involving 349 articles from 2010-2018 suggests that factors interfering with dengue prevention practices are divided into two, namely:\n\n1. the internal factors that encompass attitudes and perceptions of dengue prevention\n\n2. and the environmental factors such as weather, drainage systems, buildings designed with unreachable rain gutters and poor drainage and piping systems.\n\nTo mitigate the ongoing dengue problem, the government must prioritize densely populated areas like Selangor and Kuala Lumpur, focusing not only on these environmental factors but also on the internal factors that drive residents’ prevention practices. An effective strategy for combating dengue requires addressing residents’ understanding of their vulnerability to infection and the severity of its potential impact. The Health Belief Model (HBM), a widely used framework in public health, provides valuable insights into how individuals’ perceptions influence their health-related behaviors. It explains that people are more likely to adopt preventive measures when they perceive themselves to be at risk (perceived susceptibility) and understand the serious consequences of the disease (perceived severity). In the context of dengue prevention, if residents recognize their vulnerability to infection and believe that the impact of dengue can be severe, they are more likely to take appropriate actions, such as eliminating mosquito breeding sites and using protective measures. According to Glanz et al. (2008), the HBM underscores the importance of addressing both external conditions and internal beliefs to effectively promote behavior change and eventually for this particular case, reduce the spread of dengue ( Figure 3).\n\nResidents of low-income communities may underestimate their susceptibility to the virus. Environmental factors such as overcrowded living conditions and poor waste management in these areas create ideal breeding grounds for mosquitoes. They are the ones vulnerable to the financial burden of contracting dengue. A single day of lost income due to illness can have dire economic consequences for households already struggling to make ends meet.\n\nDengue fever is often referred to as a disease prevalent in poor areas, and closely linked with impoverished populations. The World Health Organization categorises dengue fever as one of the neglected tropical diseases (NTDs), which are indicative of poverty, and recommends interventions targeted at populations in poverty-stricken and marginalised communities to address dengue (Mulligan et al., 2015).\n\nIn Malaysia, where dengue remains a significant public health threat, there is a notable scarcity of data on the national understanding of dengue infection, as well as on public attitudes and preventive practices. Therefore, this study aimed to assess the knowledge, attitudes, and preventive practices of a low-income community consisting of 16,000 residents in a densely populated area of Kuala Lumpur. The results of this study are expected to contribute to the development of evidence-based community health intervention programs that specifically target homeowners’ preventive practices. These findings will enhance our understanding of the factors influencing knowledge, attitudes, and practices among low-income, community-dwelling adults and provide public health authorities with crucial insights for prioritizing actions in similar settings across Malaysia.\n\n\nMethods\n\nStudy design and setting\n\nA community-based, cross-sectional study was conducted over 4 weeks in July 2024 among adult residents of four low-cost housing apartments under the People’s Housing Programme (Program Perumahan Rakyat or PPR) in the federal constituency in Kuala Lumpur, Malaysia. In 1998, the National Housing Department of the Malaysian Ministry of Housing and Local Government (Jabatan Perumahan Negara) developed the PPR to provide affordable housing for Malaysians of low socioeconomic status with a monthly household income below RM 3,000 (Goh et al., 2011).\n\nThe four participant PPRs in this study were PPR Sri Pantai, PPR Pantai Ria, PPR Kampung Limau and PPR Seri Cempaka. These PPRs were chosen for their proximity to the Klang River, which creates significant challenges for vector control due to stagnant water that serves as breeding grounds for Aedes mosquitoes. Our aim is to assess the community’s understanding of these risks to develop an effective health intervention for this vulnerable area.\n\nDengue has been confirmed in this community, as shown by the DENV-positive mosquito pools recorded in the table below based on a 2021 study by the National Institute of Health in collaboration with the University of Malaya (Wan et al., 2021). We have specifically chosen this community for the survey because such areas, especially near water bodies, are prone to recurrent outbreaks, highlighting the necessity of continuous monitoring and targeted interventions ( Figure 4).\n\nSource: 2021 study by the National Institute of Health in collaboration with the University of Malaya (Wan et al., 2021).\n\nEach of these PPRs comprises multistorey apartments that are labelled as blocks. PPR Sri Pantai has two 21-storey blocks namely, Block 100 and 102 with 20 units on each floor. Each of the four blocks A, B, C and D of PPR Pantai Ria has 17 floors, with a total of 20 units per floor. Block 96 and Block 94 of the PPR Kampung Limau are 17-storeyed with 20 units per floor. The Seri Cempaka PPR consists of two 17-storey blocks, ‘E’ and ‘F’. To minimize sampling bias, a structured design was used, with the sampling frame drawn from four PPR areas. Stratified random sampling ensured proportional representation from all floors of each apartment block. Data collection included weekends to ensure broader resident participation. This approach helped capture a diverse and representative sample, reducing the risk of bias related to availability or uneven representation.\n\nThe sample size is calculated using the Krejcie and Morgan sample size calculation method (Krejcie and Morgan, 1970) to ensure it is representative of the entire population.\n\nSample size calculation: The formula for the Krejcie and Morgan sample size calculation is as follows:\n\n• s = required sample size\n\n• X2 = the table value of chi-square for 1 degree of freedom at the desired confidence level (3.841 for 95% confidence level)\n\n• N = the population size\n\n• P = the population proportion (assumed to be 0.5 for maximum sample size)\n\n• d = the degree of accuracy expressed as a proportion (0.05 for 95% confidence level)\n\nUsing this formula, the following sample sizes have been calculated for the populations. The estimated sample size for each of the PPRs based on the total population is shown in Table 2.\n\nThe structured questionnaire was adapted from the validated Malay version developed by Mac Guad et al. (2021). Permission to use the questionnaire and scoring system was obtained from the authors. The questionnaire was divided into four sections:\n\n1. Socio-demographic Information: This section gathered data on age, gender, ethnicity, marital status, education level, occupation, household income, and family size.\n\n2. Knowledge (Part A): Nine questions assessing respondents’ knowledge of dengue transmission, symptoms, and prevention.\n\n3. Attitudes (Part B): Eight questions gauging attitudes toward dengue prevention measures and public health policies.\n\n4. Practices (Part C): Eleven questions focusing on the respondents’ actual behaviors in preventing dengue, such as eliminating mosquito breeding sites and using preventive measures.\n\nThe KAP scores were calculated, with high KAP defined as achieving 80% or more of the maximum possible score, and low KAP defined as scores below this threshold (Elia-Amira et al., 2023).\n\nRespondents’ dengue knowledge, attitude, and practices (KAP) were categorised as “Good” or “Poor” based on predefined scoring criteria ( Table 4).\n\nBelow are the criteria used for each domain:\n\n1. Knowledge: Respondents were assessed on their knowledge about dengue through a total of 25 questions, which included sub-questions under 9 main topics. To be categorized as having “good” knowledge, respondents needed to answer at least 20 questions correctly (80% or more). Those who scored below 20 were classified as having “poor” knowledge.\n\n2. Attitude: The attitude section contained 8 questions. A score of 6 or more correct answers indicated a good attitude toward dengue prevention, while scores below 6 were categorized as poor attitude.\n\n3. Practices: There were 11 questions assessing preventive practices against dengue. Respondents who correctly answered 9 or more questions were classified as practicing good preventive measures, while those scoring below 9 were considered to practice poor dengue prevention.\n\nData analysis was conducted using IBM-SPSS Statistics version 25. Descriptive statistics, including frequencies and percentages, were used to describe the population characteristics and summarize participants’ knowledge, attitudes, and practices (KAP) related to dengue prevention. Logistic regression was used to identify potential predictors among the sociodemographic variables. Variables with a significance level of p ≤ 0.25 in univariate analysis were further analyzed using multiple logistic regression to determine independent predictors of high or low KAP levels. A p-value of ≤ 0.05 was considered statistically significant.\n\nEthical approval for this study was obtained from the Institutional Review Board (IRB) of Taylor’s University Center for Research Management, with approval number HEC 2024/179, granted on June 20, 2024. The study adhered to the ethical principles outlined in the Declaration of Helsinki. Written informed consent was obtained electronically via a Google form. Participants were fully informed about the study’s purpose, and their rights to privacy and confidentiality were upheld. All collected data were anonymized to protect participants’ identities, and they were notified of their right to withdraw from the study at any time without any repercussions.\n\n\nResults\n\nThe study collected 1,636 responses, with the majority being females (56.8) and Malays (78.3%). Most respondents were married (70.9%) and had secondary level education (64.4%). Of the total population, 47.35% are not working, with almost half being housewives at 26.3%, while the remainder consists of those who are either retired at 10.3% or unemployed at 10.7%, A significant portion earned less than RM2500 monthly (62.4%) (Table 3) I (extended data).\n\nIn this community, 76.7% of participants exhibited poor knowledge and 83.1% had a negative attitude towards dengue, despite 66.7% demonstrating good prevention practices ( Table 4).\n\nKnowledge\n\nMost residents (77.7%) had limited knowledge about dengue. Most of the participants had correctly identified the symptoms, i.e. fever (88.9%) and nausea (68.2%) as symptoms, but wrongly identified cough (47.1%) and swollen glands (32%). Majority of the residents correctly identified mosquito behavior, but 43.3% incorrectly believed there’s a specific treatment for dengue. Most recognized the importance of rest (82.6%) and hydration (90.2%) for recovery, and 90.8% were aware of fines for mosquito larvae on their property (Table 5) (extended data).\n\nAttitude\n\nIn terms of attitudes towards dengue prevention, a significant portion of residents (62.3) believe that killing the mosquitoes is the only way to prevent infection, with 66.8 percent trusts in fogging as a way of control. And the majority agrees (74.6%) that fines help in the control and believes that dengue is preventable (60.2%) ( Table 6).\n\nPractice\n\nMost residents engaged in good dengue prevention practices. Out of the 11 dengue practices, majority about 75% of the respondents answered yes to all the questions, except with the Abate use (54.4%) ( Table 7).\n\nKnowledge predictors\n\nTo identify predictors of dengue knowledge, attitudes, and preventive practices, we initially conducted a univariate logistic regression analysis. Variables that demonstrated a significance level of 0.25 were subsequently included in a multivariate analysis. Among all tested variables, only PPR (Public Housing Program), marital status, and education level emerged as independent predictors of dengue knowledge.\n\nThe analysis revealed that residents from PPR Pantai Ria were 1.7 times more likely to have a higher level of dengue knowledge compared to those from PPR Sri Pantai (p = 0.004). Similarly, residents from PPR Sri Cempaka and PPR Kampung Limau demonstrated 2.8 times (<p = 0.001). and 3.2 times (p ≤0.001) higher odds, respectively, of possessing greater dengue knowledge relative to those from PPR Sri Pantai.\n\nIn terms of marital status, married residents were 3 times more likely to have good dengue knowledge compared to widowed or divorced residents (p = 0.007). This suggests that marital status, alongside location, plays a critical role in influencing residents’ awareness and understanding of dengue prevention and control.\n\nEducational attainment is also an important predictor of dengue knowledge (p value≤0.002), even though no individual education level (primary, secondary, tertiary) showed a statistically significant association (Table 8) (extended data).\n\nAttitude predictors\n\nAll variables were initially tested using univariate logistic regression to assess predictors of dengue-related attitudes, and those with a significance level of 0.25 were included in a multivariate analysis. Among the variables examined, only the PPR community was identified as a significant predictor of dengue attitude.\n\nResidents of PPR Pantai Ria were found to be 2.7 times more likely to demonstrate a positive attitude towards dengue prevention compared to those from PPR Sri Pantai (p value≤0.001), while PPR Kampung Limau were 2 times more likely to exhibit favorable attitudes towards dengue prevention as compared to residents of PPR Sri Pantai (p value ≤0.001) (Table 9) (Extended data).\n\nPreventive Practices predictors\n\nTo identify predictors of dengue preventive practices, we performed a univariate logistic regression analysis on all variables, followed by multivariate analysis for those with a significance level of 0.25. Our findings revealed three significant predictors of good preventive practices: PPR community, marital status, and previous infection with dengue.\n\nIn terms of the PPR communities, residents of PPR Pantai Ria were 2.7 times more likely to engage in dengue preventive practices compared to those from PPR Sri Pantai. Similarly, residents from PPR Sri Cempaka and PPR Kampung Limau had odds ratios of 1.9 (p < 0.001) and 1.7 (p < 0.001), respectively, for practicing dengue prevention relative to PPR Sri Pantai.\n\nMarital status was another significant predictor. Both single and married individuals had higher odds of practicing dengue prevention compared to widowed or divorced residents, with odds ratios of 1.9 for singles (p = 0.015) and married individuals (p = 0.007), respectively.\n\nInterestingly, prior infection with dengue was also a significant predictor. Those who had previously been infected with the virus were 1.5 times more likely to engage in preventive practices compared to those who had never experienced dengue (p = 0.047). This suggests that personal experience with the disease can enhance adherence to preventive measures (Table 10) (extended data).\n\n\nDiscussion\n\nThe overall findings of this survey underscore the urgent need for the community to recognize the significance of their preventive practices. Despite demonstrating good preventive measures, approximately three-fourths of the population exhibit poor knowledge about dengue, raising concerns for the future. While these practices are commendable, sustaining them is vital, particularly considering escalating dengue threats exacerbated by climate change in the coming years.\n\nInterestingly, Malaysia ranks first in implementing preventive measures according to a recent global systematic review and meta-analysis of knowledge, attitudes, and practices regarding dengue fever among the general population (Jahromi et al., 2024; Aung et al., 2016; Yussof et al., 2017). This achievement may be attributed to the high incidence of dengue in the country, prompting residents to receive education on appropriate preventive actions.\n\nHowever, a discrepancy exists between attitudes and knowledge in this particular community. Typically, one would expect that individuals with strong knowledge and understanding of dengue would translate this knowledge into effective practices. Conversely, those with poor knowledge are likely to neglect preventive measures (Naqvi et al., 2024; Selvarajoo et al., 2020). In this specific community, however, the situation appears different. Many residents engage in preventive behaviours not necessarily because they fully understand the disease or possess a positive attitude toward dengue prevention, but rather probably out of a sense of obligation or expectation given that the country is experiencing high incidence of dengue.\n\nTo enhance community understanding and sustain such practices, a targeted community-based health education program is recommended. This program should focus on bridging the knowledge gap by providing interactive workshops, accessible educational materials, and practical demonstrations. Engaging local leaders and healthcare providers can foster a supportive environment that encourages active participation.\n\nIn the analytical analysis, the findings indicate that the PPR community is a significant independent predictor across the domains of dengue knowledge, attitude and preventive practices, with residents from various neighbourhoods such as Pantai Ria, Sri Cempaka, and Kampung Limau exhibiting different levels in comparison with Sri Pantai. These discrepancies are likely influenced by variations in access to health education, community engagement initiatives, and available resources.\n\nA meta-analysis by O’Mara-Eves et al. (2015) emphasizes that localized interventions can substantially improve community health outcomes by raising awareness and mobilizing local resources. Engaging communities through targeted initiatives has shown positive effects on diverse health outcomes. Therefore, it is imperative for community leaders to play an active role in fostering collaborative efforts, such as organizing clean up drives or informative sessions, and designing health education campaigns that resonate with the specific needs and preferences of their communities. By facilitating inclusive activities that engage all residents, these community-driven initiatives can enhance health-related attitudes and promote proactive measures for dengue prevention, thereby contributing to improved public health outcomes.\n\nMarital status emerged as a significant predictor of both dengue knowledge and preventive practices, with married individuals showing higher levels of engagement in dengue prevention, likely due to their increased responsibilities toward family health, particularly in households with children. Family dynamics and social support networks positively influence health-related behaviours (Tunçgenç et al., 2023). Strategies must address the knowledge gaps and prevention behaviours among singles, widows, and divorced individuals, as these groups may not experience the same social pressures or support systems that encourage active participation in health initiatives. Tailored campaigns should be developed to help these individuals understand their personal risk and the importance of dengue prevention. Community leaders can foster a “family-like” environment, promoting mutual trust and commitment to collective well-being. By building a sense of community responsibility, individuals who may otherwise feel disconnected from health initiatives can be encouraged to participate.\n\nLastly, previous infection with dengue was identified as a significant predictor of preventive practices. Individuals who have experienced dengue firsthand are likely more aware of its impact and the importance of prevention. Personal experience with health issues often drives individuals to adopt more proactive health behaviours (Short and Mollborn, 2015). Prior to infection, many may not have engaged in preventive practices; however, the experience of contracting dengue and the associated physical, emotional, and financial hardships appear to motivate behaviour change. Once individuals recognize their susceptibility to the disease and face consequences such as loss of income or the burden on their families, they become more likely to adopt preventive measures.\n\nPublic health education should leverage these insights by focusing on the tangible risks and consequences of dengue, particularly for those in vulnerable communities. Educational campaigns should highlight the specific conditions that increase susceptibility to the disease, such as overcrowded living environments, proximity to stagnant water, and inadequate waste disposal. It’s essential to make the connection between these environmental factors and their practical implications, like loss of income, disruption of family life, and the severe health risks, including fatal outcomes, associated with dengue. By personalizing these risks and emphasizing the potential for severe illness, public health messaging can resonate more deeply and encourage sustained community engagement in dengue prevention efforts.\n\n\nConclusion\n\nThe findings of this survey underscore the need for the community to deepen their understanding of the relevance of their preventive practices. Although preventive behaviours are generally strong, three-fourths of the population exhibit poor knowledge of dengue, which may hinder the sustainability of these practices in the long term, particularly as the threat of dengue is exacerbated by climate change. The PPR community has been identified as a significant independent predictor of dengue-related knowledge, attitudes, and preventive practices. Marital status is an independent predictor of both dengue knowledge and preventive practices, and a history of prior dengue infection is a predictor of increased engagement in preventive practices.\n\nEthical approval for this study was obtained from the Institutional Review Board (IRB) of Taylor’s University Center for Research Management, with approval number HEC 2024/179, granted on June 20, 2024. The study adhered to the ethical principles outlined in the Declaration of Helsinki. Written informed consent was obtained electronically via a Google form, ensuring voluntary participation. Participants were fully informed about the study’s purpose, and their rights to privacy and confidentiality were upheld. All collected data were anonymized to protect participants’ identities, and they were notified of their right to withdraw from the study at any time without any repercussions.",
"appendix": "Data availability\n\nDataverse: “Understanding the future of Dengue in Malaysia: Assessing Knowledge, Attitude, and Homeowner Practices in Mitigating Climate-Driven Risks”, https://doi.org/10.7910/DVN/9VNEET (Galvan, 2024).\n\nThis project contains the following underlying data:\n\n1. The raw file in Excel “LEMBAH PANTAI RAW DATA-1”\n\n2. The tables in the Results section (Tables 3-10) “PPR Lembah Pantai TABLES”\n\n3. The raw file in SPSS “SPSS LEMBAH PANTAI FINAL CLEAN”\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nDataverse: “Understanding the future of Dengue in Malaysia: Assessing Knowledge, Attitude, and Homeowner Practices in Mitigating Climate-Driven Risks”, https://doi.org/10.7910/DVN/9VNEET (Galvan, 2024).\n\nThis project contains the following extended data:\n\n1. The questionnaire includes the full set of questions used to assess participants’ knowledge, attitudes, and practices related to dengue prevention in the Lembah Pantai area.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgment\n\nThis research project was conducted under the purview of Taylor’s Education Sdn Bhd, in collaboration with Prudential Assurance Malaysia Berhad. Special thanks are due to the PPR Leaders of the Lembah Community: Encik Zol, Encik Nizam, Haji Zakaria, and Encik Mohammad for their commitment to the fight against dengue in their communities. We would also like to express our appreciation to Puan Salamah, whose pivotal role in facilitating collaboration within the community was instrumental. Finally, we extend our heartfelt gratitude to the entire Lembah Pantai community for graciously allowing us to conduct this research in their neighborhoods, and to our Batch 21 Year Three Medical Students for their dedicated efforts in data collection. We acknowledge Prudence Foundation as the project funder and Taylor’s University, Malaysia, for their support in publishing this article.\n\n\nReferences\n\nAung MMT, Hassan AB, Kadarman NB, et al.: Knowledge, attitude, practices related to dengue fever among rural population in Terengganu, Malaysia. Malaysian Journal of Public Health Medicine. 2016; 16(2): 15–23.\n\nBujang MA, Mudin RN, Haniff J, et al.: Trend of dengue infection in Malaysia and the forecast up until year 2040. Internal Medicine Journal. 2017; 24(6): 438–441.\n\nChem YK, Yenamandra SP, Chong CK, et al.Molecular epidemiology of dengue in Malaysia: 2015–2021. Frontiers in Genetics. 2024; 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElia-Amira NMR, Chen CD, Low VL, et al.: Economic status as the predictor of dengue awareness among local residents of Sabah, Malaysia. Journal of Integrated Pest Management. 2023; 14(1). Publisher Full Text\n\nGalvan JA: Understanding the future of Dengue in Malaysia: Assessing Knowledge, Attitude, and Homeowner Practices in Mitigating Climate-Driven Risks. Harvard Dataverse. 2024; V3. Publisher Full Text\n\nGlanz K, Rimer BK, Viswanath K: Health behavior and health education: Theory, research, and practice. 4th ed.Jossey-Bass; 2008.\n\nGoh AT, Tee A, Yahaya A: Public low-cost housing in Malaysia: Case studies on PPR low-cost flats in Kuala Lumpur. Journal of Design and Built Environment. 2011; 8(1).\n\nGuad RM, Sim MS, Wu YS, et al.: Knowledge, attitude, and prevention practice on dengue and dengue seroprevalence in a dengue hotspot in Sabah, East Malaysia. Research Square. 2021. Publisher Full Text\n\nIDengue_Versi 3.0: iDengue_Versi 3.0.2024, May 10. Reference Source\n\nJahromi AS, Jokar M, Abdous A, et al.: Global systematic review and meta-analysis of knowledge, attitudes, and practices towards dengue fever among the general population. Asian Pacific Journal of Tropical Medicine. 2024; 17(5): 191–207. Publisher Full Text\n\nKrejcie RV, Morgan DW: Determining sample size for research activities. Educational and Psychological Measurement. 1970; 30: 607–610. Publisher Full Text\n\nLenharo M: Dengue is breaking records in the Americas — what’s behind the surge? Nature. 2023. PubMed Abstract | Publisher Full Text\n\nMinistry of Health, Malaysia: Kenyataan media Ketua Pengarah Kesihatan – Situasi semasa demam denggi di Malaysia minggu epidemiologi 18/2023 (30 April – 06 Mei 2023). Ministry of Health Malaysia; 2023. Retrieved October 15, 2024. Reference Source\n\nMd Taib N, Atil A: Tackling dengue issues need proactive measures: A narrative review of current level of prevention and control of dengue in Malaysia. Archives of Epidemiology & Public Health Research. 2023; 2(1). Publisher Full Text\n\nMulligan K, Dixon J, Sinn CL, et al.: Is dengue a disease of poverty? A systematic review. Pathogens and Global Health. 2015; 109(1): 10–18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNaqvi SAA, Sajjad M, Tariq A, et al.: Societal knowledge, attitude, and practices towards dengue and associated factors in epidemic-hit areas: Geoinformation assisted empirical evidence. Heliyon. 2024; 10(1): e23151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Mara-Eves A, Brunton G, Oliver S, et al.: The effectiveness of community engagement in public health interventions for disadvantaged groups: A meta-analysis. BMC Public Health. 2015; 15: 129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPelan Strategik Pencegahan dan Kawalan Denggi Kebangsaan 2022 – 2026: Sektor Penyakit Bawaan Vektor Bahagian Kawalan Penyakit Kementarian Kesihatan Malaysia. 2022. Retrieved November 5, 2024. Reference Source\n\nSa-Ngamuang C, Lawpoolsri S, Yin MS, et al.: Assessment of malaria risk in Southeast Asia: A systematic review. Malaria Journal. 2023; 22(1): 339. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSelvarajoo S, Liew JWK, Tan W, et al.: Knowledge, attitude and practice on dengue prevention and dengue seroprevalence in a dengue hotspot in Malaysia: A cross-sectional study. Scientific Reports. 2020; 10(1): 9534. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShort SE, Mollborn S: Social determinants and health behaviors: Conceptual frames and empirical advances. Current Opinion in Psychology. 2015; 5: 78–84. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTan SC, Gerard G: Dengue cases up by 235% in the last six months. Star. 2024, June 12. Reference Source\n\nTee GH, Yoep N, Jai AN, et al.: Prolonged dengue outbreak at a high-rise apartment in Petaling Jaya, Selangor, Malaysia: A case study. Journal of Tropical Medicine. 2019. Publisher Full Text\n\nTunçgenç B, van Mulukom V , Newson M: Social bonds are related to health behaviors and positive well-being globally. Science Advances. 2023; 9(2): eadd3715. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVieira RFC, Muñoz-Leal S, Faulkner G, et al.: Global climate change impacts on vector ecology and vector-borne diseases. Modernizing Global Health Security to Prevent, Detect, and Respond. Elsevier; 2024; pp. 155–173. Publisher Full Text\n\nWan Najdah WMA, Ahmad R, Mohamed Nor Z, et al.: Spatial Distribution of Mosquito Vector in Dengue Outbreak Areas in Kuala Lumpur and Selangor, Malaysia. Serangga. 2021; 26(3): 110–139.\n\nWan-Fei K, Sin Wan T, Alias N, et al.: Dengue mortality in Malaysia.2024; 2023. Reference Source\n\nWorld Health Organization: Dengue and severe dengue. World Health Organization; 2024. Reference Source\n\nWorld Health Organization: Fact sheet about malaria. World Health Organization; 2023. Reference Source\n\nYussof FM, Hassan A, Zin T, et al.: Knowledge of dengue among students in Universiti Sultan Zainal Abidin (UNISZA), Terengganu, Malaysia, and the influence of knowledge of dengue on attitude and practice. Journal of Fundamental and Applied Sciences. 2017; 9(2S): 199–216.\n\nZaki R, Roffeei SN, Hii YL, et al.: Public perception and attitude towards dengue prevention activity and response to dengue early warning in Malaysia. PLoS One. 2019; 14(2): e0212497. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "352160",
"date": "17 Jan 2025",
"name": "Juraina Abd-Jamil",
"expertise": [
"Reviewer Expertise infectious diseases",
"vector-borne",
"dengue"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper is very well written and easy to read and understand. The authors have made extensive literature review and the study objectives very clear. Was there a specific reason that this study was conducted at only low-cost housing areas? Kindly include this in the manuscript. The present study used structured questionnaires by Mac Guad et al (2021). Were terms used in the questionnaires adapted from the original questionnaires or changed to suit the needs of the present study? For example, terms such as “dengue carriers” – that ought to be referred to as “dengue vectors”. Dengue carriers refer to the disease host carrying the virus. In addition, distinction between dengue virus and “dengue” the disease should be made clear in the survey as well. Consequently, were respondents assisted when answering the survey questions (to prevent any misunderstanding)? Kindly indicate in the manuscript what measures were taken to prevent or address any confusion or misunderstanding that might have masked true reflection of the respondent’s KAP on dengue. Age stratification of respondents is not included in the manuscript. It would be interesting to see the respondents’ responses in the different age groups. Categorisation of KAP is only divided to 2 groups, which are good or poor. Such categorisation is very limiting and does not reflect those individuals who had some knowledge on dengue, or some good attitude in preventing dengue. This group category should be captured considering that the study target group comes from lower socioeconomic background.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1355
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https://f1000research.com/articles/13-1352/v1
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11 Nov 24
|
{
"type": "Case Report",
"title": "Case Report: Bilateral Spigelian Hernia With Meckel’s diverticulum",
"authors": [
"Younis Mohamed",
"Ahmed Hussein",
"Baber Chaudhary",
"Omar Elsaba",
"Mahmoud Rhodes",
"Ahmed Hussein",
"Baber Chaudhary",
"Omar Elsaba",
"Mahmoud Rhodes"
],
"abstract": "Spigelian hernia is an uncommon form of ventral hernia, with an incidence ranging from 0.1% to 2%. This case report describes a 72-year-old female who presented with an obstructed right Spigelian hernia, a left Spigelian hernia, and an uncomplicated Meckel’s diverticulum, along with the management approach. The patient had experienced intermittent tenderness in the right iliac fossa for the last two months, which had worsened to severe pain over the previous two days, accompanied by a palpable mass in the right lower quadrant. An urgent CT scan of the abdomen and pelvis revealed an obstructed right Spigelian hernia containing dilated proximal small bowel, and a left uncomplicated spigelian hernia. The patient experienced worsening abdominal pain and vomiting. Emergency laparotomy was performed, revealing a right Spigelian hernia with viable small bowel loops, a non-complicated Meckel’s diverticulum located 20 cm from the ileocecal valve, and a small left Spigelian hernia. The right Spigelian hernia was repaired using intraperitoneal sublay mesh, while the left hernia was treated with primary repair. No bowel resection was performed at the site of the Meckel’s diverticulum, as it was non-inflamed, to prevent contamination of the mesh with bowel flora. Bilateral Spigelian hernias accompanied by Meckel’s diverticulum present a challenging clinical scenario. Although rare, this condition should be considered in the differential diagnosis of acute abdominal pain due to the potential for serious complications.",
"keywords": [
"#meckel´s diverticulum",
"#spigelian hernia",
"#emergency exploration",
"#bilateral spigelian hernia",
"#acute abdomen"
],
"content": "Introduction\n\nSpigelian hernia is a rare form of ventral hernia. It involves the protrusion of preperitoneal fat, peritoneal sac, or intra-abdominal organs through a defect in the Spigelian aponeurosis, which lies between the rectus abdominis muscle medially and the semilunar line laterally. The Spigelian aponeurosis, formed by the fusion of the internal oblique and transversus abdominis aponeuroses, constitutes a structurally vulnerable region of the abdominal wall, predisposing it to herniation under conditions of elevated intra-abdominal pressure. Predisposing factors include obesity, chronic obstructive pulmonary disease (COPD), prior abdominal surgery, and trauma. While most Spigelian hernias are acquired, congenital forms have also been reported, potentially due to embryological defects in the development of the abdominal musculature.1’\n\nSpigelian hernias are challenging to diagnose clinically because the defect is often masked by the overlying external oblique aponeurosis, making it difficult to detect on physical examination. As a result, patients may present acutely with complications such as incarceration, strangulation, or bowel obstruction. Given the high risk of these complications, Spigelian hernias are not suitable for conservative management, and surgical intervention is the recommended treatment in both elective and emergency cases.2\n\nThis case report presents a patient with an obstructed right lower quadrant Spigelian hernia, as well as a left-sided Spigelian hernia accompanied by a non-complicated Meckel’s diverticulum, which was successfully managed through open laparotomy.\n\n\nCase presentation\n\nA 72-year-old female with a history of bronchial asthma, obesity, and left-sided breast cancer treated with mastectomy, currently on Anastrozole therapy, in addition to anxiety and depression history, presented to the emergency department with progressively worsening right iliac fossa pain over the past two days. The pain had been intermittent for two months. She also reported the presence of a palpable mass in the right lower quadrant, accompanied by nausea and multiple episodes of vomiting the previous night. Her bowel habits were normal, and there was no per-rectal bleeding.\n\nOn physical examination, significant tenderness was noted in the right iliac fossa, and a firm mass was palpated along the lateral border of the rectus abdominis muscle, approximately midway between the umbilicus and the symphysis pubis. The mass became more prominent when the patient was examined in a standing position and was associated with voluntary guarding. Symptomatic relief was provided with analgesics and antiemetics. Laboratory investigations revealed a white cell count of 9,700 WBC/μL, hemoglobin of 146 g/dL, platelet count of 366,000 platelets/μL. A contrast-enhanced CT scan of the abdomen and pelvis (Figure 1) identified a right-sided Spigelian hernia containing small bowel loops, with proximal small bowel dilatation suggestive of developing obstruction, with incidental findings included a simple liver cyst and a bulky uterus. After discussing the surgical options, the patient consented to proceed with an open laparotomy.\n\nPreoperative preparation involved keeping the patient nil by mouth (NBM), administering intravenous fluids (IVF), obtaining an electrocardiogram (ECG), scheduling the operating room, securing informed consent, performing a blood group and save, administering symptomatic medications, and conducting an anesthetic review. The procedure was performed under general and local anesthesia, with prophylactic intravenous antibiotics administered within one hour prior to the incision.\n\nDuring surgery, a lower midline incision was made. A Meckel’s diverticulum was identified approximately 20 cm from the ileocecal valve. Although bruised, it was not inflamed, so it was left intact to avoid contamination of the mesh with bowel flora. Bilateral hernial defects were observed, with the right hernia being larger than the left. Both defects were located adjacent to the lateral rectus sheath, and the right Spigelian hernia contained small bowel loops and preperitoneal fat. The small bowel loops were examined up to the duodenojejunal (DJ) junction, with no abnormalities detected. The right Spigelian hernial sac was opened, and its contents were inspected. The hernia defect was closed from the peritoneal side using 2-0 Vicryl sutures, and a 6×11 cm Prolene mesh was placed in a sublay position deep to the rectus muscle. The left Spigelian hernia was repaired using primary suture closure with 2-0 Prolene. A transversus abdominis plane (TAP) block was administered by the anesthetist. Postoperatively, the patient was advised to resume oral intake and continue antibiotic therapy for 48 hours (Figure 2).\n\nOn postoperative day 1, the patient experienced moderate abdominal pain, multiple episodes of greenish vomiting, with absence of bowel movements, abdominal bloating, and reduced urine output of less than 30 mL/hour. Intravenous fluids were administered, and a nasogastric tube (NGT) and urinary catheter were inserted. Oral intake was limited to sips of water. A chest and abdominal X-ray revealed atelectasis and dilated small bowel loops (Figure 3).\n\nBy postoperative day 2, the patient’s symptoms persisted, and blood tests showed elevated inflammatory markers: CRP of 246 mg/L, WCC of 11.5 × 109/L, hemoglobin of 122 g/L, and platelet count of 358 × 109/L. Due to concern for an intraperitoneal collection or bowel perforation, a CT abdomen and pelvis (CTAP) was performed, revealing multiple distended small bowel loops with air-fluid levels, consistent with postoperative ileus (Figure 4).\n\nBy postoperative day 3, the patient passed a bowel movement and began mobilizing with physiotherapy assistance. Initially, she did not meet the physiotherapy assessment criteria, but her physical performance gradually improved in the following days. By postoperative day 6, she was able to mobilize independently and was discharged home. A follow-up appointment was scheduled for six weeks later.\n\n\nDiscussion\n\nSpigelian hernia is a rare abdominal wall defect, with its incidence peaking between the 4th and 7th decades of life. A slight female predilection has been noted, with a male-to-female ratio of 1:1.183. The hernia occurs within the “Spigelian belt,” a 6 cm wide zone along the Spigelian line extending caudally from the umbilicus to the inferior epigastric vessels. Based on the relationship to these vessels, Spigelian hernias are classified into two types: high hernias (cranial to the vessels) and low hernias (caudal to the vessels, within Hesselbach’s triangle).3\n\nSeveral theories explain the etiology of Spigelian hernias. Cooper’s vascular-nervous theory suggests weakening of the Spigelian belt due to the deep iliac branch of the inferior epigastric vessels penetrating the aponeurosis. Zimmerman’s musculo-aponeurotic fasciculation theory is more widely accepted, proposing that infiltration of preperitoneal fat weakens the deep fibrous musculature, predisposing it to herniation (Figure 5). Other theories, such as the embryologic transition theory and Watson and Iason’s theory, implicate areas of lower resistance between developing abdominal wall muscles and weaknesses at the junction of the semilunar line and arcuate line, respectively. Risk factors for Spigelian hernia include obesity, chronic obstructive pulmonary disease (COPD), prior abdominal surgery, trauma, and conditions increasing intra-abdominal pressure.4\n\nA) External oblique. B) Internal oblique. C) Transverse abdominis. D) Hernia sac with contents. E) Spigelian fascia. F) Rectus abdominis.\n\nClinically, Spigelian hernias often evade early detection due to their deep location beneath the external oblique aponeurosis, making physical examination findings subtle or absent. Early symptoms can be nonspecific, ranging from vague abdominal discomfort to a palpable lump. However, the risk of complications, including incarceration (reported in 24–27% of cases) and strangulation (2–14%), is significant. These risks arise from the formation of a “rigid neck” in the hernial sac, particularly due to the Spigelian fascia’s fibrous bands. In this patient, morbid obesity and chronic cough associated with asthma likely contributed to the hernia formation, and she presented with a tender right iliac fossa mass, which was confirmed on CT imaging to be an obstructed Spigelian hernia, a situation warranting urgent surgical intervention.5\n\nImaging is critical in diagnosing Spigelian hernias, especially given their frequent misdiagnosis in early stages. Computed tomography (CT) is the preferred modality for identifying the defect, its size, and contents, for appropriate surgical planning. In this case, CT identified the hernia and confirmed small bowel involvement, indicating impending obstruction and urgent surgical management. While physical examination alone often fails to detect Spigelian hernias, imaging techniques such as ultrasound and CT are crucial for early diagnosis and surgical planning.6\n\nSurgical intervention is the definitive treatment for Spigelian hernia, with both open and laparoscopic approaches offering these options based on patient factors, hernia characteristics, available resources, and the surgeon’s expertise. Laparoscopic repair is gaining popularity due to its advantages of better bilateral visualization, detection of contralateral defects, and shorter recovery times. However, open repair offers superior intra-operative direct visualization and dissection, particularly for larger or more complex hernias. Both approaches aim for complete defect closure, typically reinforced with mesh to reduce the risk of hernia recurrence.7\n\nMesh reinforcement is strongly recommended in both open and laparoscopic spigelian hernia repairs, as outlined by the European Hernia Society (EHS) guidelines. Various mesh techniques exist, each selected based on the hernia size and complexity8:\n\n1. Primary Suture Repair: Suitable for small hernias, it involves closing the defect with non-absorbable sutures. However, it carries a higher recurrence risk for larger hernias.\n\n2. Onlay Mesh Repair: A synthetic mesh is placed on the anterior rectus sheath to reinforce the defect, but it may cause complications such as seroma or wound infection.\n\n3. Sublay Mesh Repair (Retromuscular/Subfascial): Mesh is placed between the rectus muscle and posterior rectus sheath. This technique provides robust support with fewer complications, making it ideal for complex or recurrent hernias.\n\n4. Inlay Mesh Repair: Mesh is positioned directly within the defect, offering simplicity but a higher recurrence risk due to incomplete coverage.\n\n5. Preperitoneal Mesh Repair: Mesh placement in the preperitoneal space reduces mesh-related complications and is less invasive but can be technically demanding.\n\n6. Component Separation Technique: This involves mobilizing abdominal muscles to close large defects without tension, potentially with mesh reinforcement. It allows closure of large defects but is more invasive and associated with higher wound complication risks.\n\nIn this case, the patient underwent open sublay mesh repair for the right-sided Spigelian hernia, while the left-sided hernia was repaired with primary sutures. This approach allowed for thorough intraoperative inspection of the hernia contents and effective defect closure. Although the recovery was prolonged by postoperative ileus, the patient showed gradual improvement and was successfully discharged.\n\nUltimately, the choice between open and laparoscopic repair depends on the hernia’s complexity and the surgeon’s expertise. Both approaches, when paired with mesh reinforcement, offer effective and durable repair modalities, with laparoscopic techniques gaining favor for their minimally invasive nature and faster recovery times.\n\n\nConclusion\n\nSpigelian hernia often presents a diagnostic challenge due to its lack of distinct physical findings, leading to frequent delays in diagnosis. A high index of clinical suspicion is essential, given the potential for complications such as bowel obstruction and strangulation. Fortunately, in this case, the patient presented with clear symptoms, allowing for timely surgical intervention and successful repair. Computed tomography (CT) imaging played a crucial role in confirming the diagnosis, and in instances where imaging is inconclusive, open laparotomy provides superior visualization and access to the peritoneal cavity, facilitating thorough inspection, especially in complex cases involving the small bowel and Meckel’s diverticulum.\n\nSurgical intervention remains the cornerstone of treatment for Spigelian hernia, as supported by the literature. In this case, open repair with a Sublay Mesh technique was performed, placing the mesh between the rectus abdominis muscle and the posterior rectus sheath to reinforce the defect. While Spigelian hernias are rare, their high risk for acute complications necessitates that they remain a differential diagnosis in patients presenting with abdominal pain. Early recognition and prompt surgical management are key to preventing adverse outcomes.\n\n\nConsent for publication\n\nA written informed consent for publication was obtained from the patient and the co-authors for this case report, including the publication of any identifying data related to the clinical history, images, and findings. The patient has provided informed written consent, acknowledging the inclusion of relevant medical information for educational and research purposes. All efforts were made to ensure that the patient’s identity remains protected and anonymized throughout the report. This consent is in accordance with the ethical guidelines and institutional policies governing the protection of patient privacy and confidentiality.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nWeber RV, Hunt ZC, Kralovich KA: Spigelian Hernia: Repair and Clinical Presentation. Am. Surg. 2002; 68: 965–967.\n\nLosanoff JE, Richman BW, Jones JW: Spigelian Hernia: Review of 1 Case and Surgical Anatomy. Am. Surg. 2002; 68(3): 264–268. Publisher Full Text\n\nMoreno-Egea A, Carrasco L, Girela E, et al.: Open vs Laparoscopic Repair of Spigelian Hernia: A Prospective Randomized Trial. Arch. Surg. 2002; 137: 1266–1268. PubMed Abstract | Publisher Full Text\n\nRíos A, Munitiz V, Alcaraz P, et al.: Spigelian Hernia: Bibliographical Study and Presentation of a Series of 28 Patients. Hernia. 2005; 9: 36–41. Publisher Full Text\n\nSkandalakis PN, Zoras O, Skandalakis JE, et al.: Spigelian Hernia: Surgical Anatomy, Embryology, and Technique of Repair. Am. Surg. 2006; 72: 42–48. PubMed Abstract | Publisher Full Text\n\nO’Dwyer PJ, Doran H, Kiely EM: Spigelian Hernia: The Role of Imaging in Diagnosis and Surgical Management. Hernia. 2001; 5: 109–113. Publisher Full Text\n\nKilic A, Scott JW, McLemore EC, et al.: Laparoscopic Versus Open Repair of Spigelian Hernias: A Review of 22 Years of Experience. Surgery. 2015; 159: 7–10. Publisher Full Text\n\nEuropean Hernia Society: European Hernia Society Guidelines on the Management of Spigelian Hernias. Hernia. 2020; 24: 1407–1414. Publisher Full Text"
}
|
[
{
"id": "340369",
"date": "19 Nov 2024",
"name": "Atif Iqbal",
"expertise": [
"Reviewer Expertise General surgery articles"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article describes a 72-year-old female presenting with bilateral Spigelian hernias & an uncomplicated Meckel's diverticulum. Key clinical details include: Symptoms, Diagnostics, Management and Outcome. Strengths: 1. Comprehensive Case Description: Detailed reporting of the patient's history, clinical findings, diagnostic imaging, and treatment 2 Visual Aids: High quality imaging and diagrams provide clarity on the surgical approach 3 Detailed Discussion: Thoroughly examines the rarity of the condition , challenges in diagnosis and its importance in acute abdominal pain differential diagnosis. 4 Well constructed case report. Areas for Improvement There is always room at the top. Article is well written and comprehensive. If authors could mention BMI of the patient and urea/creatinine/electrolytes results, article will be almost perfect. Conclusion: The case report is a valuable addition to medical literature, offering insights into a rare condition and its management. Approval Status: Approved\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "340365",
"date": "06 Dec 2024",
"name": "Barbara Yordanis Hernandez Cervantes",
"expertise": [
"Reviewer Expertise As a general surgeon",
"my scope of expertise encompasses a wide range of procedures",
"particularly abdominal surgery",
"with a focus on abdominal wall hernias",
"which represent one of the most prevalent diseases in our specialty globally."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe case is well organized and complies with the standards for case reports. Nonetheless, I like to emphasize some places where I believe enhancements are essential for optimal comprehension of the case and for educational objectives.\nCertain grammatical errors in the text and image labels require correction. The authors stated in the abstract that the mesh was placed intraperitoneally, which contradicts the case description. In the case presentation, it is essential to comprehend the history of reducibility concerning the right swelling during the last two months of intermittent abdominal pain. This information would assist in determining whether we were addressing an incarcerated hernia or a reducible hernia. Furthermore, the narrative fails to address the reducibility of the mass during the two days of exacerbated discomfort, prompting me to conclude that it was irreducible. The physical examination lacks details regarding the left abdominal swelling, if present, and does not provide information on the assessment of the remaining abdominal quadrants, as bowel sounds are not noted as a significant indicator of intestinal obstruction. During the research, I noted that an accessible and effective method, such as abdominopelvic ultrasonography, was not employed (for what reason?). The surgical treatment does not clarify whether the Meckel’s diverticulum was included in the hernia sac; it is noted that the diverticulum exhibited bruising (what was the cause of this?). A visual representation is absent; however, it would benefit the surgical community, particularly since the decision was made not to resect the diverticulum, acknowledging that potential complications such as inflammation, bleeding, and obstruction may arise in the future. Due to the patient's paralytic ileus in the postoperative phase, a serum electrolyte test may be conducted, as it plays a crucial part in the condition's pathogenesis. This case report pertains to Spigelian hernias with Meckel's diverticulum. Nonetheless, I did not locate any information pertaining to the correlation and care of Meckel's diverticulum and hernias during the discussion of the case. Aside from two references, the remainder are over a decade old. Conclusions: In addition to these particulars, the case report is highly engaging and informative for the entire medical community, particularly the surgical sector.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1352
|
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